uws sensory neuroscience symposium 2014 · 9:00 – 10:00 keynote lecture chair: carl parsons...

UWS Sensory Neuroscience

Symposium 2014

Dear Colleagues Welcome to the School of Medicine, and to the fifth UWS Sensory Neuroscience Symposium. Since the inaugural meeting in 2010, the Symposium has provided a forum for researchers to discuss their latest research into sensory neuroscience in a relaxed atmosphere. The University of Western Sydney is proud to sponsor this event, and to support prizes for scientific excellence: this year we are, once again, offering the $1000 UWS Sensory Neuroscience Prize for the best presentation by a postdoctoral researcher and for the best presentation by a higher-degree research student. We have selected 15 talks from the submitted abstracts and are delighted to have Professor Dexter Irvine opening the Symposium with the Keynote Lecture titled: Auditory Cortex Plasticity and Changing Conceptualization of Auditory Cortical Receptive Fields. We hope you enjoy the symposium and look forward to your participation. With best wishes

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John Morley Vaughan Macefield Carl Parsons David Mahns Rachael Brown

UWS Sensory Neuroscience Symposium School of Medicine, UWS Campbelltown Monday 8 December 2014

8:30 – 9:00 REGISTRATION & COFFEE

9:00 – 10:00

KEYNOTE LECTURE Chair: Carl Parsons Dexter Irvine (Bionics Institute & School of Psychological Sciences, Monash University) Auditory cortex plasticity and changing conceptualization of auditory cortical receptive fields

10:00 – 10:30 MORNING TEA

10:30 – 12:00

SESSION I Chair: Paul Martin Morven Cameron (UWS) External electrical stimulation activates voltage-gated potassium currents Heba Khamis (UNSW) Evidence for a mechanism of sensing grip security during object manipulation Mohammad Rehmanjan (UWS) Somatotopic mismatch of hand representation in stroke patients Jason Potas (ANU) Red light (670 nm) treatment improves functional and cellular outcomes following spinal cord injury Michelle Rank (UoN) The spinal cord that changes itself: spontaneous changes in interneuron properties after incomplete spinal cord injury Melissa Tadros (UoN) Ventro-dorsal development of intrinsic and action potential properties in spinal sensory and motor circuits of the human fetus

12:00 – 2:00 LUNCH & POSTERS

UWS Sensory Neuroscience Symposium School of Medicine, UWS Campbelltown Monday 8 December 2014

2:00 – 3:15

SESSION II Chair: Richard Vickery James Fallon (Bionics Institute) Effects of cochlear implant use on binaural processing David Grenet (NeuRA) Auditory vection and associated eye movements John G L Morris (Westmead Hospital) Does blinking reduce image blur resulting from head turns, in birds? Jennifer Robertson (ANU) Using hyper-excitability to probe primary olfactory cortex networks Malinda Tantirigama (ANU) Representation of odour by two classes of principal neurons in the mouse piriform cortex in vivo

3:15 – 3:30 AFTERNOON TEA

3:30 – 4:30

SESSION III Chair: Robert Callister Kristen Farrell (UoN) A new method for studying inputs from the gastrointestinal tract: implications for the study of visceral pain and inflammatory bowel disease Peter Shortland (UWS) Nerve injury and pain: what the erk is all the fos about? Siobhan Schabrun (UWS) Investigation of the motor cortex in the transition from acute to maintained pain using a novel experimental pain model Vaughan Macefield (UWS) Knee joint taping improves proprioceptive acuity at the knee and improves gait in humans devoid of muscle spindles

4:30 – 5:30 POSTERS & AWARDS / DRINKS & CANAPES

UWS Sensory Neuroscience Symposium School of Medicine, UWS Campbelltown Monday 8 December 2014 Keynote Lecturer Professor Dexter Irvine Bionics Institute & School of Psychological Sciences, Monash University BIOGRAPHY Professor Dexter Irvine completed a BA (Hons) degree in Psychology at the University of Sydney in 1966 and a PhD in auditory neuroscience at Monash University in 1971. After post-doctoral training at the University of Western Australia and the University of California at Irvine, he joined the Department of Psychology at Monash University. He has spent periods as a visiting research fellow at the University of Heidelberg, the University of Wisconsin (Madison), and the University of Washington (Seattle). He held a Personal Chair at Monash from 1994 until his retirement in 2005, and is now an Emeritus Professor in the Sub-Faculty of Psychological and Biomedical Sciences and a Fellow of the Academy of Social Sciences in Australia. He currently has a part-time position as a Professorial Research Fellow at the Bionics Institute.

Throughout his career, Professor Irvine’s research has been directed to a number of aspects of central auditory processing, notably mechanisms of sound localization and the functional organization of the auditory cortex. Over the last twenty-five years, his work has focused on plasticity in the adult auditory system. He has published a monograph on auditory brainstem processing, a co-edited book on auditory spectral processing, and approximately 125 peer-reviewed publications and book chapters on various aspects of the neural mechanisms of hearing. The research group with which he works at the Bionics Institute has used animal models to examine changes in auditory cortex organization and responsiveness as a consequence of profound deafness and of cochlear implant use. More recent projects have been concerned with the integration of acoustic and electrical information in the auditory cortex of animals with residual hearing, and the processing of binaural information in the midbrain of profoundly deaf animals with bilateral cochlear implants.

UWS Sensory Neuroscience Symposium School of Medicine, UWS Campbelltown Monday 8 December 2014 Chair: Carl Parsons Keynote Lecture 9:00 – 10:00 am AUDITORY CORTEX PLASTICITY AND CHANGING CONCEPTUALIZATION OF AUDITORY CORTICAL RECEPTIVE FIELDS Dexter Irvine Bionics Institute & School of Psychological Sciences, Monash University [email protected] The receptive fields (RFs) of neurons in primary sensory cortices were traditionally thought to be modifiable during critical/sensitive period during development, but to be stable in the adult brain. In the primary auditory cortex (AI) spectral tuning, and the associated tonotopy, was thought to simply reflect highly organized topographic projections from the periphery. However, AI neurons in adults have been found to manifest a remarkable degree of plasticity under a range of circumstance where patterns of input or the behavioural significance of particular inputs are modified. The fundamental substrates of plasticity in spectral RFs have been revealed by intracellular recording, anatomical, and more recent high-resolution two-photon imaging studies. AI neurons receive subthreshold input over a much wider range of frequencies than is apparent from the “classical” RFs defined by spiking activity. In accordance with this observation, anatomical tracing studies indicate that a given region of AI receives inputs from a wide range of intrinsic and extrinsic sources, much of it via horizontal cortico-cortical projections. Only a tiny fraction of the input to a particular region is derived via projections from the thalamic lemniscal-line nucleus. Two-photon imaging has been used to detect tone-evoked calcium transients in single spines in AI pyramidal neurons and has revealed remarkable heterogeneity of the frequency tuning of individual spines along single dendrites. Auditory cortical RFs should therefore be considered as highly modifiable contrast filters, changes in the relative effectiveness of different inputs presumably involving well-established processes that allow synaptic weights to be changed over relatively short time scales. The evidence on the effects of attention indicates that particular subsets of the diverse inputs to a given cortical neuron can be gated by top-down influences, and it is likely that the organism can switch rapidly between different sets of inputs depending on the task being performed.

UWS Sensory Neuroscience Symposium School of Medicine, UWS Campbelltown Monday 8 December 2014 Chair: Paul Martin Session 1 10:30 – 10:45 am EXTERNAL ELECTRICAL STIMULATION ACTIVATES VOLTAGE-GATED POTASSIUM CURRENTS Morven Cameron University of Western Sydney [email protected] Morven Cameron1, Amr Al Abed2, John Morley1 1 University of Western Sydney 2 University of New South Wales Neuroprosthetic devices aim to activate neurons in the most efficient and specific way. To do this, these devices take advantage of the intrinsic expression of voltage-gated ion channels that open in response to a change in the cell membrane potential. The most widely studied of these are the voltage-gated sodium channels (Nav), as their activation usually gives rise to action potentials. However, several other classes of voltage-gated channels exist that likely contribute to the probability of successful neuronal stimulation. We specifically analysed the response of voltage-gated potassium channels in retinal neurons to external electrical stimulation with patch-clamp electrophysiology (voltage-clamp) and computational modeling. We found that due to the brief nature of external electrical stimulation the currents elicited were essentially “tail currents”. The cell is depolarized long enough to open these potassium channels but the membrane potential is then quickly returned to resting levels due to the very brief nature of external electrical stimulation. The current recorded reflects the closing kinetics of the activated channel(s). In the case of Kv channels, calcium-activated potassium channels (KCa) contribute the majority of the current, although delayed rectifier and fast transient Kv channels also play a role. Consequently, the likelihood of activating a neuron with electrical stimulation relies on the expression levels of these Kv channels, and likely plays a large role in the probability of action potential generation.

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UWS Sensory Neuroscience Symposium School of Medicine, UWS Campbelltown Monday 8 December 2014 Session 1 10:45 – 11:00 am EVIDENCE FOR A MECHANISM OF SENSING GRIP SECURITY DURING OBJECT MANIPULATION Heba Khamis University of New South Wales [email protected] Heba Khamis1,2, Stephen J Redmond1, Vaughan G Macefield2,3, Ingvars Birznieks2,4 1 Graduate School of Biomedical Engineering, University of New South Wales 2 Neuroscience Research Australia 3 School of Medicine, University of Western Sydney 4 School of Medical Sciences, University of New South Wales Currently, little is known about how humans modulate grip force during dexterous object manipulation. A mechanism is present here, by which humans may sense grip security and impending loss of grip. Microneurography was performed to record the responses of five fast adapting type-I (FA-I) tactile afferents with receptive fields located in the fingerpads of the index and middle fingers of three human subjects. Using a six-axis force-controlled KUKA robot, three textured plastic disks were pressed onto the fingerpads with a 4 N normal force. A tangential force, which ultimately resulted in an overt slip, was then generated by moving the disk by 10 mm at 2.5 mm/s in the ulnar or distal directions. This procedure was performed using clean disks, disks with added oil to reduce friction, and added friction increasing agent. The fingertip forces, which were recorded with an ATI Nano17 force/torque sensor, were used to detect overt slips. Four of the five FA-I afferents consistently fired before overt slip. These afferents are unlikely to respond to the slow rate of increasing tangential force, implying they are instead responding to localised slips [1] between the fingertip and disk in the slipping zone which is expected to be in the periphery of the stable contact zone [2]. This may serve as a trigger to modulate grip force in order to avoid impending overt slip. Furthermore, the ratio of tangential to normal force at the time of the first spike was correlated with coefficient of friction (r-squared = 0.30-0.87), with direction differences in some cases. These results demonstrate that FA-I afferents can encode information about grip security, which is sufficient to perform grip force adjustments during object manipulation in reference to the grip safety margin rather than in reference to an explicit measure of coefficient of friction. [1] R.S. Johansson, and G. Westling, Signals in tactile afferents from the fingers eliciting adaptive motor responses during precision grip. Exp. Brain. Res. 66, 141-154 (1987) [2] B. Delhaye, P. Lefèvre and J-L Thonnard, Dynamics of fingertip contact during the onset of tangential slip, J. R. Soc. Interface 11: 20140698


UWS Sensory Neuroscience Symposium School of Medicine, UWS Campbelltown Monday 8 December 2014 Session 1 11:00 – 11:15 am SOMATOTOPIC MISMATCH OF HAND REPRESENTATION IN STROKE PATIENTS Mohammad Rehmanjan University of Western Sydney [email protected] Rehmanjan M1, Nguyen T1,2, McIntyre S3,4, Levy S1,5, Steel K3, Hoque S6, Logina I7, Wasner G8, Vickery R4,9, Birznieks I4,9 1 School of Medicine, University of Western Sydney 2 Department of Rehabilitation, Camden Hospital 3 School of Science and Health, University of Western Sydney 4 Neuroscience Research Australia 5Department of Neurology, Campbelltown Hospital 6 Department of Physiotherapy, Nepean Hospital 7 Department of Neurology, Riga Stradins University, Riga, Latvia 8Department of Neurology and the Division of Neurological Pain Research and Therapy, University Clinic of Schleswig-Holstein, Kiel, Germany 9School of Medical Sciences, University of New South Wales Damage to the somatosensory cortex due to stroke may change the orderly spatial representation of tactile stimuli (somatotopic maps). Up until now there are only few reports of isolated cases in stroke patients. The aim of the current study was to test a group of patients to demonstrate whether such dysfunction may be found by systematic testing. Semmes-Weinstein monofilaments calibrated above the detection thresholds were used to test twenty-five predefined sites on the glabrous skin of each hand. Three patients with extensive lesions involving the middle cerebral territory were identified to show different forms of somatotopic mismatch. Patient 1 had normal detection thresholds and a systematically shifted somatotopic representation on the affected hand with a significant amount of stimuli referred to a focal point between the index finger and thumb. Patient 2 had normal detection thresholds, but labile distorted somatotopic maps on the affected hand. Patient 3 showed high detection thresholds and scrambled somatotopic maps. This study has demonstrated different types of abnormalities in tactile stimulus localisation indicating distorted somatotopic maps in stroke patients. Further studies should evaluate whether new specially designed rehabilitation strategies may achieve normalisation of somatotopic maps and functional recovery in such patients with somatotopic mismatch.


UWS Sensory Neuroscience Symposium School of Medicine, UWS Campbelltown Monday 8 December 2014 Session 1 11:15 – 11:30 am RED LIGHT (670 nm) TREATMENT IMPROVES FUNCTIONAL AND CELLULAR OUTCOMES FOLLOWING SPINAL CORD INJURY Jason Potas Australian National University [email protected] Di Hu, Shuyu Zhu, Jason R Potas Australian National University Photobiomodulation has been reported to result in improvements following trauma to nervous tissues. We examined the effect of 670 nm light treatment on locomotor recovery, behavioural signs of pain, dorsal column functional integrity and cellular changes following spinal cord injury. Male Wistar rats received a T10 hemi-contusion spinal cord injury and divided into treated (SCI670) and sham treated (SCI) groups. SCI670 rats received 30 min daily exposures to a 670 nm LED array (60 mW/cm2), while SCI rats were restrained under the same conditions without light treatment. After 7 days, 6 regions over the animals’ dorsum were tested for hypersensitivity to an innocuous poke to Above, At and Below the T10 dermatomes on both the ipsi- and contralateral sides to the injury. Red light significantly reduced Below level hypersensitivity (SCI, n=12; SCI670, n=14; p= 0.047) on the ipsilateral side, and trends were observed on the Below contralateral region and ipsi- and contralateral At level regions (p≤0.099). Animals were then anaesthetised with urethane (1.4 mg/kg i.p.) for electrophysiological evaluations. Somatosensory surface potentials recorded from the dorsal column nuclei evoked from left and right sural nerve stimulations revealed that SCI resulted in a reduction in magnitudes of evoked responses [(injured side)/(intact side)] to 63±6% compared to intact animals (102±12%), which was partially restored by light treatment (93±17%). Similarly, latency differences [(intact side) – (injured side)] of the SCI group (0.49±0.10 ms) was restored by light treatment (0.06±0.13 ms; p=0.01). In another group of animals, immunohistochemistry revealed that 670 nm treatment reduced cell death and microglia/macrophage recruitment, but increased the proportion of the anti-inflammatory M2 macrophage subtype. Treatment also increased axonal sprouting, particularly to the contralateral side, over a 7 day time course. These findings suggest that 670 nm light alters cellular conditions following spinal cord injury leading to a variety of improved functional outcomes.


UWS Sensory Neuroscience Symposium School of Medicine, UWS Campbelltown Monday 8 December 2014 Session 1 11:30 – 11:45 am THE SPINAL CORD THAT CHANGES ITSELF: SPONTANEOUS CHANGES IN INTERNEURON PROPERTIES AFTER INCOMPLETE SPINAL CORD INJURY Michelle Rank University of Newcastle [email protected] MM Rank1, JR Flynn1, MP Galea2, R Callister1, RJ Callister1 1Biomedical Sciences & Pharmacy, University of Newcastle 2Department of Medicine (Royal Melbourne Hospital), University of Melbourne Following incomplete spinal cord injury (SCI) some spontaneous recovery of function occurs. In rodent models of SCI, particularly in mice, the degree of spontaneous recovery exceeds that observed in humans, or even in other animal models of SCI (eg. cat). The specific cellular mechanisms underlying this spontaneous recovery of function, during the transition from acute to chronic stages of injury, are unknown. Here we characterize the changes to intrinsic cellular and synaptic properties of spinal interneurons occurring in the acute (4 wks post SCI) and chronic (10 wks) stages of SCI in an adult mouse hemisection model of injury. Male mice (C57Bl/6; ~P63) received a spinal hemisection (T9-10). After acute or chronic recovery periods, horizontal spinal cord slices (T6-T12, 250 µm) were prepared for whole cell patch clamp electrophysiology. Recordings were made from deep dorsal horn (DDH) interneurons located within two spinal segments of the SCI. Input resistance and rheobase current were decreased in chronic versus acute SCI mice and resting membrane potential was more depolarized in interneurons from chronic SCI mice. In response to depolarising current injection, DDH interneurons exhibit four action potential discharge patterns: tonic firing, initial bursting, delayed firing and single spiking. The proportion of neurons exhibiting each discharge pattern differed significantly in acute versus chronic SCI mice. Moreover, the expression of several voltage-activated subthreshold currents known to underlie differences in AP discharge categories in DDH interneurons also differed between acute and chronic groups. Spontaneous excitatory postsynaptic currents (sEPSCs) were recorded to assess excitatory synaptic drive. sEPSC frequency did not change however sEPSC amplitude, rise-time and decay time increased over time post-injury. Together these data indicate that DDH interneurons in the chronic stages of SCI are characterized by altered excitability, reduced excitatory synaptic drive, and either altered expression of glutamate receptor subtypes or receptor location on their somatodendritic trees.


UWS Sensory Neuroscience Symposium School of Medicine, UWS Campbelltown Monday 8 December 2014 Session 1 11:45 – 12:00 pm VENTRO-DORSAL DEVELOPMENT OF INTRINSIC AND ACTION POTENTIAL PROPERTIES IN SPINAL SENSORY AND MOTOR CIRCUITS OF THE HUMAN FETUS Melissa Tadros University of Newcastle [email protected] Melissa A Tadros1, Rebecca Lim1, David I Hughes2, Alan M Brichta1, Robert J Callister1 1School of Biomedical Sciences & Pharmacy, Faculty of Health and Medicine, Hunter Medical Research Institute, University of Newcastle 2Spinal Cord Research Group, Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, United Kingdom The spinal cord is critical for modifying and relaying sensory information to, and motor commands from, higher centres in the central nervous system to initiate and maintain contextually relevant locomotor responses. Our understanding of how spinal sensorimotor circuits are established during in utero development is based largely from studies in rodents. In contrast, there is little functional data on the development of sensory and motor systems in humans. Here, we use patch clamp electrophysiology to examine the development of neuronal excitability in human fetal spinal cords (10-18 weeks gestation; WG). Transverse spinal cord slices (300 µm thick) were prepared and recordings were made from visualized neurons in either the ventral (VH) or dorsal (DH) horn at 32oC. Action potentials (APs) could be elicited in VH neurons throughout the period examined, but only after 16 WG in DH neurons. At this age, VH neurons discharged multiple APs, whereas most DH neurons discharged single APs. At 16-18 WG VH neurons also displayed lower input resistances, and larger AP and after-hyperpolarization amplitudes than DH neurons. Between 10 and 18 WG the intrinsic properties of VH neurons changed markedly, with input resistance decreasing and AP and AHP amplitudes increasing. Together, our data suggest spinal neurons mature electrophysiologically along a ventro-dorsal gradient, with motor circuits maturing well before the sensory circuits involved in processing tactile and nociceptive information.


UWS Sensory Neuroscience Symposium School of Medicine, UWS Campbelltown Monday 8 December 2014 Chair: Richard Vickery Session 2 2:00 – 2:15 pm EFFECTS OF COCHLEAR IMPLANT USE ON BINAURAL PROCESSING James Fallon Bionics Institute & University of Melbourne [email protected] James B Fallon, Sam Irving, Andrew K Wise, Dexter RF Irvine Bionics Institute & the University of Melbourne Bilateral cochlear implantation is increasingly common, particularly for young children, and results in an increase in performance for both sound localization and speech discrimination in noise compared to unilateral implantation. However, the improvements are small and performance remains inferior to that of normal listeners. Animal and psychophysical studies have shown that long-term deafness from a young age degrades processing of interaural time differences (ITDs) but not interaural level differences (ILDs). The effects of chronic bilateral cochlear implant use on binaural processing are less clear; therefore we examined the effects of chronic bilaterally cochlear implant use on ITD and ILD sensitivity in long-term neonatally deafened animals. Three groups of cats were used: two normal hearing controls (NHC), two neonatally profoundly deafened unstimulated cats (NDUS) and four neonatally profoundly deafened cats that received approximately 6 months of bilateral intra-cochlear electrical stimulation from clinical cochlear implants and speech processors (NDS). Single-unit responses (n= 110, 60, 86 for the NHC, NDUS and NDS groups respectively) to electric binaural stimulation with a range of ITDs and ILDs were bilaterally recorded from both central nuclei of the inferior colliculus using 32-channel silicon arrays (NeuroNexus). ITD sensitivity was significantly poorer in both the neonatally deafened groups compared to the normal hearing animals (Kruskal-Wallis test, p < 0.05), and there was no difference between the stimulated and unstimulated groups (p > 0.05). ILD sensitivity was not different between the groups (p > 0.05). Conclusions: The use of bilateral clinical cochlear implants does not prevent/reverse the degradation in ITD processing that occurs following long-term deafness from a young age. Whether experience with appropriate ITD cues would improve ITD processing still needs to be examined. ILD processing is largely unaffected by either long-term deafness or chronic stimulation.


UWS Sensory Neuroscience Symposium School of Medicine, UWS Campbelltown Monday 8 December 2014 Session 2 2:15 – 2:30 pm AUDITORY VECTION AND ASSOCIATED EYE MOVEMENTS David Grenet Neuroscience Research Australia & University of New South Wales [email protected] David Grenet, Richard Fitzpatrick Neuroscience Research Australia & University of New South Wales Illusory movement or vection produced by a moving visual field is a well-known phenomenon. In this study we investigated vection produced by a moving sound field. Subjects’ ears (pinnae) were cast in silicone rubber. The silicone ears were mounted on a mannequin head and microphones were placed under them at the external auditory canal. Sound stimuli created a soundscape that was picked up by these microphones and played to the subject through headphones as they sat in a dark, sound-attenuating booth. Thus, the subject heard the soundscape as if he or she was at the position of the mannequin head. We rotated the mannequin head in yaw at 4 speeds (5, 10, 20 and 50 º/s) both left and right. All subjects reported feeling some sensation of movement in response to the stimuli. Of the total 64 trials from the 8 subjects who showed clear responses, 55 showed a perception of movement in response to the stimulus, and 44 were in the predicted direction. This auditory vection has similar strength to vection induced by a moving visual field. Exploratory data was also collected to determine whether this illusion of self-motion is accompanied by involuntary compensatory eye movements (nystagmus). One subject wore an infrared eye tracking camera (EyeSeeCam, Germany) while being exposed to the same stimuli as above. Small (<5 º) eye movements were observed that were correlated with the stimulus and displayed the characteristics of the nystagmus associated with visually (optokinetic) and vestubular evoked nystagmus. The slow-phase velocity of this nystagmus was 1-3 º/s for a 50 º/s stimulus. These data, while preliminary, are in stark contrast to optokinetic nystagmus, which in optimum conditions has unity gain. This suggests that the contributions of different sensory systems are weighted differently for perception and ocular-motor reflexes.


UWS Sensory Neuroscience Symposium School of Medicine, UWS Campbelltown Monday 8 December 2014 Session 2 2:30 – 2:45 pm DOES BLINKING REDUCE IMAGE BLUR RESULTING FROM HEAD TURNS, IN BIRDS? John GL Morris Westmead Hospital [email protected] John GL Morris1, Donald K Morris2 1Emeritus Clinical Neurologist, Westmead Hospital, Sydney 2Past Lecturer in Zoology, Central Queensland University It has been noted in birds that blinking, the transient and repetitive closure of the eyes, often appears to coincide with head movement. To clarify this association, blinks were video-ed and analysed frame by frame in 195 species of bird covering 22 Orders. Phasic (rapid, 50-100msec) blinks, often linked to head/eye movement, were performed by the nictitating membrane in most birds. We have called these ‘nict blinks’. In three Orders, Columbiformes, Psittaciformes and Strigiformes, phasic blinks involved the upper eyelid, ‘upper lid blinks’. In drowsiness and in preening in all birds, tonic (slow, 200-1000msec) blinks were seen. These mainly involved the lower eyelid, ‘lower lid blinks’. Combinations of these three types of blink were common, especially nict blinks with minimal lowering of the upper eyelid. Saccadic oscillations (high frequency bursts of low amplitude eye jerks thought to improve retinal perfusion), were observed during blinking when filming at 200 frames/second. Blinks usually coincided with or preceded head turns and the duration of the blinks showed a strong correlation with the duration of the head turn. A case is made for blinking having a role in reducing image blur associated with rapid head or eye movement, fulfilling the same role as saccadic suppression in humans.


UWS Sensory Neuroscience Symposium School of Medicine, UWS Campbelltown Monday 8 December 2014 Session 2 2:45 – 3:00 pm USING HYPER-EXCITABILITY TO PROBE PRIMARY OLFACTORY CORTEX NETWORKS Jennifer Robertson Eccles Institute of Neuroscience [email protected] Robertson JJ, Bekkers JM Eccles Institute of Neuroscience, John Curtin School of Medical Research, Australian National University The primary olfactory cortex (POC) is the first site of odour processing in the cortex. It combines chemical odour information from the olfactory bulb with information from other brain regions to form our perception of smell. Grossly, it has a “simple” trilaminar structure, which masks the complexity of its internal connectivity. Recent studies have shown that the probability of two adjacent cells in the POC being connected is lower than in the neocortex and, unlike in the neocortex, this connection probability does not decay with distance. Here, we examined network activity in the POC in vitro by increasing the excitability. We also studied the neocortex and the hippocampus, for comparison. Two-photon Ca2+ imaging was used to monitor the simultaneous activity of 20-60 neurons in 450 µm-thick slices from 18-30 day-old C57Bl6 mice. Hyper-excitability was generated by perfusing the slices with artificial cerebrospinal fluid containing no added Mg2+ and high K+ (0Mg/HK), a common in vitro epilepsy model. Next, we applied an electrical stimulus via a bipolar stimulating electrode placed in the association layers. We found that in the POC, before electrical stimulation, the neurons exhibited unsychronised activity (n=49 slices), and after mild stimulation the synchrony increased (p<0.001, n=15 slices). Thus, mild electrical stimulation can dramatically alter patterns of hyper-excitability in the POC. In contrast, in the hippocampus (n=7) and the neocortex (n=6) the neurons were synchronised prior to electrical stimulation and stimulation had no further effect. The mechanism underlying the change in the pattern of hyperexcitability in the POC is unknown, but presumably it involves some form of long-lasting synaptic plasticity. Further work on mechanisms may provide insights into the connectivity of this complex network and how it is able to process olfactory information.


UWS Sensory Neuroscience Symposium School of Medicine, UWS Campbelltown Monday 8 December 2014 Session 2 3:00 – 3:15 pm REPRESENTATION OF ODOUR BY TWO CLASSES OF PRINCIPAL NEURONS IN THE MOUSE PIRIFORM CORTEX IN VIVO Malinda Tantirigama Eccles Institute of Neuroscience [email protected] Malinda LS Tantirigama, John M Bekkers Eccles Institute of Neuroscience, John Curtin School of Medical Research, Australian National University The anterior piriform cortex (aPC) is a relatively simple paleocortical structure dedicated to processing odour information. The aPC is highly laminar, with its main input layer (layer 2) containing two distinct populations of glutamatergic neurons: semilunar (SL) cells in layer 2a and superficial pyramidal (SP) cells in layer 2b. However, little is known about how odour information is represented in neuronal populations in different layers. Here, we simultaneously measured the activity of up to 158 neurons in each layer of the aPC in anesthetised mice in vivo using 2-photon microscopy and functional calcium imaging, employing the calcium indicator dye Cal-520, or the genetically encoded calcium sensor GCaMP6s. With the higher signal-to-noise ratio of Cal-520 and GCaMP6s, we detected spontaneous activity in the somata of SL and SP cells, as well as in their dendrites in layer 1. Presentation of a palette of seven structurally-distinct odorants excited up to 15 % of neurons in an ensemble pattern that was unique for each odorant. On average, a given SL or SP cell responded to 0.5 of seven odorants. However, the distribution of the number of odours that each cell responded to was 6.6 times more positively skewed in SP cells than in SL cells, indicating that responsive SP cells are excited by a larger number of odorants. These results suggest that SL and SP cells are spontaneously active in the mouse aPC and may employ distinctive codes for representing odours in vivo.


UWS Sensory Neuroscience Symposium School of Medicine, UWS Campbelltown Monday 8 December 2014 Chair: Robert Callister Session 3 3:30 – 3:45 pm A NEW METHOD FOR STUDYING INPUTS FROM THE GASTROINTESTINAL TRACT: IMPLICATIONS FOR THE STUDY OF VISCERAL PAIN AND INFLAMMATORY BOWEL DISEASE Kristen Farrell University of Newcastle [email protected] Kristen E Farrell, Brett A Graham, Simon Keely, Robert J Callister Biomedical Sciences and Pharmacy, University of Newcastle Chronic pain is a major problem for patients with inflammatory bowel disease, and is thought to involve plasticity within the spinal cord dorsal horn (DH). In the context of visceral pain, little is known about the functional properties of neurons that receive inputs from the colon. Accordingly, we developed a mouse in vivo preparation, to study intrinsic and synaptic properties of DH neurons receiving input from the colon. Methods: Mice (C57Bl/6J, male, 6-7 weeks) were anaesthetised, and a laminectomy was performed over the L6-S1 spinal segments. A recording pipette was lowered into the grey matter of the DH and patch-clamp recordings were made from laminae I-II neurons. Each neuron’s response to current injection, colon distension (via balloon catheter) and cutaneous stimulation were examined. Results: Responses to colonic distension (pressures >80 mmHg) were observed in 7/81 laminae I-II neurons. Action potentials were generated in three of these neurons and subthreshold responses were observed in four neurons. All seven distension-sensitive neurons responded to brushing or pinching of the hindpaw or tail. Distension-sensitive neurons exhibited tonic or initial bursting action potential discharge during depolarising current injection, as well as excitatory and/or inhibitory post-synaptic potentials. A variety of firing patterns and spontaneous neural activity were also observed in distension insensitive neurons. Based on what we know about DH neurons our preliminary data suggest distension sensitive neurons were inhibitory interneurons. In vivo patch clamping can be used to study the properties of DH neurons that receive input from the colon. Our new preparation will allow future detailed analysis of the mechanisms that determine DH neuron excitability in mice with normal and inflamed colons.


UWS Sensory Neuroscience Symposium School of Medicine, UWS Campbelltown Monday 8 December 2014 Session 3 3:45 – 4:00 pm NERVE INJURY AND PAIN: WHAT THE ERK IS ALL THE FOS ABOUT? Peter Shortland School of Science & Health, University of Western Sydney [email protected] Peripheral noxious stimuli not only induce an immediate sensation of pain but also produce an increased responsiveness (central sensitization) of spinal cord neurons that outlasts the initial stimulus. This central sensitization contributes to post-injury hypersensitivity (hyperalgesia and allodynia), hallmarks of peripheral neuropathic pain conditions. Noxious stimuli induce the activation of transcription factors such as c-fos or extracellular signal related kinases (p-ERK) and these can be used as an index of activation and sensitization (Harris 1998; Gao & Ji 2009). However, little is known about the neurochemical identities of neurons that express these markers or how these are affected by nerve injury. Using immunoctyochemical techniques the types of cells expressing c-fos and p-ERK before and after nerve injury were assessed using graded electrical stimuli of the sciatic nerve in the rat. Sections of lumbar spinal cord were double-labelled for c-fos and p-ERK then antibodies specific for cellular markers of subpopulations of spinal cord neurons (excitatory and inhibitory interneurons, projection neurons). Noxious stimuli in intact nerves induce c-fos & P-ERK activity in mainly excitatory neurons (70% are NK,1Glu2/3, 30% are inhibitory NOS/GluR1). Axotomy decreased the total numbers of c-fos and p-ERK cells activated by electrical stimulation of the proximal nerve. Double labelling studies showed a shift to a more excitable state in that more excitatory neurons expressed c-fos after injury than before. Stimulation of the injured nerve at A-beta strength induced c-fos but not p-ERK expression in the spinal cord neurons. Some of the c-fos neurons expressed NK1 receptors, a marker associated with known pain pathways. Together these studies show that acute noxious stimuli elicit activity in mainly excitatory neurons and this is further enhanced after nerve injury.


UWS Sensory Neuroscience Symposium School of Medicine, UWS Campbelltown Monday 8 December 2014 Session 3 4:00 – 4:15 pm INVESTIGATION OF THE MOTOR CORTEX IN THE TRANSITION FROM ACUTE TO MAINTAINED PAIN USING A NOVEL EXPERIMENTAL PAIN MODEL Siobhan Schabrun University of Western Sydney [email protected] SM Schabrun1, SW Christensen2, N Mrachacz-Kersting2, T Graven-Nielsen2 1School of Science and Health, University of Western Sydney 2Laboratory for Musculoskeletal Pain and Motor Control, Center for Sensory-Motor Interaction, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark. Primary motor cortical (M1) organisation and function are altered in persistent musculoskeletal pain and changes are associated with pain and motor dysfunction. Despite this, no study has examined M1 in the transition from acute to maintained pain. Repeated intramuscular injection of nerve growth factor (NGF) induces deep tissue hyperalgesia reminiscent of musculoskeletal pain. Here we utilised this novel model to examine the effect of M1 organisation and function in the transition from acute to maintained pain. Twelve healthy individuals received injection of NGF into the dominant extensor carpi radialis brevis (ECRB) on two days (day 0 and day 2). Quantitative sensory (pain and pain-related function) and motor testing, and assessment of M1 organisation (transcranial magnetic stimulation derived maps) and function (intracortical networks, interhemispheric inhibition), were performed prior to injection on Days 0, 2 and 4 and again on Day 14. Pain and pressure pain sensitivity in ECRB were increased in parallel with reduced function at Day 2 (all P<0.001), and further increased at Day 4 (all P<0.02). Reorganisation of M1 was evident at Day 4, characterised by increased map volume (P=0.005) and an increased number of map peaks (P=0.009). These changes were accompanied by reduced intracortical inhibition (P=0.033) and increased intracortical facilitation (P=0.004). Interhemispheric inhibition was reduced from the ‘affected’ to the ‘unaffected’ hemisphere on Day 4 (P<0.026). M1 adaptations returned towards baseline at day 14. These data indicate increased excitability of M1 for the painful muscle that is mediated by reduced GABAergic inhibition and enhanced glutamatergic facilitation in intracortical networks. Further, these data suggest a role for reduced interhemispheric inhibition in the development of bilateral sensorimotor deficits in response to pain. Our findings provide the first evidence of the nature and time-course of M1 adaptation in response to prolonged muscle pain.


UWS Sensory Neuroscience Symposium School of Medicine, UWS Campbelltown Monday 8 December 2014 Session 3 4:15 – 4:30 pm KNEE JOINT TAPING IMPROVES PROPRIOCEPTIVE ACUITY AT THE KNEE AND IMPROVES GAIT IN HUMANS DEVOID OF MUSCLE SPINDLES Vaughan Macefield University of Western Sydney [email protected] Vaughan G Macefield1, Niamh Goulding2, Lucy Norcliffe-Kaufmann2, Felicia B Axelrod2, Horacio Kaufmann2 1School of Medicine, University of Western Sydney, Australia 2Dysautonomia Center, Department of Neurology, New York University School of Medicine, New York, USA Hereditary sensory and autonomic neuropathy type III features disturbed proprioception and a marked ataxic gait; joint angle matching error is positively correlated with the degree of ataxia. We recently showed that these patients lack functional muscle spindle afferents but preserved large-diameter cutaneous afferents, suggesting that patients with better proprioception may be relying on proprioceptive cues provided by tactile afferents (Macefield et al., 2011, 2013). We tested the hypothesis that enhancing cutaneous sensory feedback by stretching the skin at the knee joint using unidirectional elasticity tape (kinesiology tape) could improve proprioceptive accuracy and gait. Proprioceptive acuity at the knee joint was measured in 18 patients with HSAN III and 14 age-matched control subjects during passive dorsiflexion and plantarflexion of the knee joint with and without taping. Knee joint positions relative to one another were recorded on digital inclinometers. Tape was applied bilaterally to the knees in an X-shaped pattern. Patients with HSAN III performed poorly on the joint angle-matching test (mean joint matching error±SE 8.6±1.1°, controls 3.0±0.3°). With taping, proprioceptive accuracy was significantly better (mean error: 5.7±0.9°), improving 36% compared to the pre-taping condition. Gait analysis revealed that the average stride width, calculated as the maximal distance between ankles during each step, decreased significantly with taping (23.7±1.5 cm) when compared to pre-taping (29.1±1.3 cm). We conclude that taping improves both proprioceptive acuity and decreases the wide-based ataxic gait associated with HSAN III, presumably via enhanced sensory feedback from preserved cutaneous afferents sensitive to tensile strain in the skin. [1] Macefield VG, Norcliffe-Kaufmann L, Gutiérrez J, Axelrod, F & Kaufmann H. (2011) Can loss of muscle spindle afferents explain the ataxic gait in Riley-Day syndrome? Brain 134: 3198-3208 [2] Macefield VG, Norcliffe-Kaufmann LJ, Axelrod F & Kaufmann H (2013) Relationship between proprioception at the knee joint and gait ataxia in HSAN III. Movement Disorders 28: 823-827


UWS Sensory Neuroscience Symposium School of Medicine, UWS Campbelltown Monday 8 December 2014 Poster Session THE ENDOCANNABINOID SYSTEM: A FUNCTIONALLY KEY COMPONENT OF RETINAL SIGNALLING Charles Yates University of Sydney [email protected] Charles Yates, Dario Protti University of Sydney Vision starts in the retina, a complex yet structurally organised extension of the brain located in the posterior eye. This remarkable piece of nervous tissue demonstrates higher order processing, a function previously thought only to occur in the brain. Phenomena such as adaptation to mean illumination and contrast adaptation are just two processes that take place. The endocannabinoid (eCB) system has been characterised in the last 15 years as a modulatory system at neuronal synapses that regulates transmitter release. Recently, the eCB system has been detected in the retina, with studies indicating functional changes after application of cannabinoid receptor ligands. Whether or not eCBs are tonically released in the retina, and their physiological function, are yet to be ascertained. This study aims to elucidate whether or not eCBs are released in physiological conditions in the retina, and if so, how they affect retinal function. The aims are to investigate how the eCB system modulates response strength of retinal ganglion cells (RGCs) to light stimulation, receptive field organisation, contrast sensitivity and short-term plasticity. Furthermore, the effects on RGC excitability were assessed by monitoring the activity of sodium and potassium channels. The study used C57/BL6J mice to perform patch-clamp recordings on RGCs of a whole-mount retina. Recordings were collected before and after bath application of URB597 (1μM), an inhibitor of the fatty acid amide hydrolase enzyme (FAAH). Inhibition of FAAH should raise the concentration of anandamide, an eCB, amplifying any tonic effect present. This study shows that application of URB597 produced a paradoxical effect at the synaptic and cellular levels on RGCs. Furthermore, eCBs, most likely anandamide, are shown to modulate various aspects of retinal processing. It is concluded that eCBs have a tonic role in the retina, and traditional cannabinoid receptors may not be the only sites of action.


UWS Sensory Neuroscience Symposium School of Medicine, UWS Campbelltown Monday 8 December 2014 Poster Session CALCIUM IMAGING OF RETINAL GANGLION CELL RESPONSES TO EXTRACELLULAR MICROELECTRODE STIMULATION Chih Yu Yang University of New South Wales [email protected] CY Yang1, AJ Woolley1,2, D Tsai1,3, GJ Suaning1, JW Morley1,2, NH Lovell1 1Graduate School of Biomedical Engineering, University of New South Wales 2School of Medicine, University of Western Sydney 3Howard Hughes Medical Institute, Biological Sciences and Bioelectronic Systems Lab, Electrical Engineering, Columbia University, USA We used electroporation techniques to load synthetic calcium dye into somata and dendrites of retinal ganglion cells (RGC) to provide a means of assessing the activation of RGCs using extracellular electrical stimulation. New Zealand White rabbit inferior peripheral retinas were cut into approximately 5 × 5 mm sections and attached photoreceptor surface down on a modified Millicell Biopore insert (Millipore). A cut retinal section was sandwiched between two custom-made platinum (Pt) electrodes with Oregon Green BAPTA-1 on top of the retina. The applied electroporation parameters were +9 or +10 V (top electrode, on GCL side), 10 ms pulse width, 1 Hz pulse frequency and 6 or 7 constant voltage square wave pulses. After electroporation, the retinal section on the membrane insert was mounted onto an imaging chamber and placed under the microscope and perfused with Ames’ medium at 2 ml/min, equilibrated with 95% O2-5% CO2 to pH 7.4 and heated to 33-35°C. Extracellular stimulation by custom-made 25 μm stimulation electrodes consisted of trains of 100 or 200 charge-balanced, cathodic-first, symmetric biphasic pulses at 333 Hz pulse frequency, each pulse with 200 or 300 µs pulse width and 5 s interval between each train. Pulse train amplitudes were incremented from 10 µA to 100 µA in 10 µA steps. RGC somatic and proximal dendritic Ca2+ signals were simultaneously recorded by two-photon microscopy. RGCs had increased Ca2+ signals in somata and dendrites following electrical stimulation. The Ca2+ signal peaks in both somata and dendrites increased with increased stimulation amplitudes and durations. Dendritic staining allowed identifications of RGC functional subtype.The electroporation technique is effective in loading calcium indicator into RGC populations in the rabbit retina, and allows assessment of functional RGC subtypes excited in response to electrical stimulation.


UWS Sensory Neuroscience Symposium School of Medicine, UWS Campbelltown Monday 8 December 2014 Poster Session FREQUENCY PERCEPTION AT MULTIPLE SKIN SITES DEPENDS ON PHASE AND SEPARATION BUT NOT AMPLITUDE OF VIBRATION Gabriel Dicander University of Sydney & Linköping University [email protected] Gabriel Dicander 1,2, Ingvars Birznieks1,3, Richard Vickery3, Sarah McIntyre1,4 1Neuroscience Research Australia 2Linköping University 3University of New South Wales 4University of Sydney Tactile stimulation of the skin will elicit activity in multiple primary afferents that differs in firing rate and latency. The differences in sensitivity and conduction velocity will produce characteristic phase shifts between these afferents’ inputs to the central nervous system. To investigate how these diverse inputs are integrated by the nervous system, we conducted a psychophysical study using two vibrating probes on the skin. The aim was to investigate the relationship of phase, spatial separation and amplitude in affecting perceived vibration frequency. The two probes terminated in spherical ends (5mm diameter), and were tested at three different separations (4, 8 and 16cm) on the palmar skin of the hand. A two-interval forced choice protocol was used, with a standard stimulus composed of two probes each vibrating at 25Hz, delivered 180° out of phase, and comparison stimuli of in-phase vibration (18 - 54Hz). All the waveforms were brief pulses of approximately 2ms duration. Participants (N = 11) judged which of the two stimuli had the highest perceived frequency. Four amplitudes were tested (10 - 120µm), but were always identical for a given standard and comparison. Perceived frequency of the out of phase probes was higher than the base frequency of 25Hz; when probe separation was 4cm, perceived frequency was higher (39Hz) than at either 8cm (32Hz, F1,10 = 117.8, p < 0.001, η2G = 0.20) or 16cm (32Hz, F1,10 = 95.9, p < 0.001, η2G = 0.18). Perceived frequency was only minimally affected by amplitude changes between 40 and 120μm for any of the distances (F2,20 = 6.4, p = 0.007, η2G = 0.06). Both phase and spatial separation strongly influence vibrotactile interaction between two skin sites. However, despite likely variation in the amount of peripheral recruitment, changes in amplitude contribute relatively little.


UWS Sensory Neuroscience Symposium School of Medicine, UWS Campbelltown Monday 8 December 2014 Poster Session

PSYCHOPHYSICAL RESPONSES TO WEAK VISUAL STIMULI REVEAL NEURON-LIKE PROPERTIES Gloria Luo-Li Sydney Medical School [email protected] Gloria Luo-Li1; David Alais2; Alan Freeman1 1Sydney Medical School 2School of Psychology, University of Sydney The visual contrast-response function in human subjects typically has low gradient at low contrast. This is inconsistent with signal detection theory, and we therefore aimed to measure precisely the contrast-response function at low contrast. Recently published work shows that light decrements are detected sooner than increments. We aimed to see whether this observation held at low contrast. Visually normal adult humans were briefly presented with horizontal grating patches. The gratings were raised-cosine in form so that each presentation provided either an increment or decrement in luminance. Either the left or right half of the grating patch was shown and subjects indicated which half had been shown. Stimuli were randomly timed, and response correctness and reaction time were recorded. There was a small range of contrasts, centred on zero, at which contrast sensitivity was indistinguishable from zero. Neurons in primary visual cortex have a resting membrane potential well below threshold: we propose that the contrast sensitivity plateau indicates the minimum contrast required to depolarise these neurons to threshold. Further, reaction times at low contrast were about 50 ms shorter for contrast decrements than for increments. This corresponds well with recently published work showing that off-dominated cortical neurons have shorter latencies to decrements that do on-dominated neurons to increments. Low-contrast measurements reveal behaviour that appears to reflect the properties of single neurons in primary visual cortex.


UWS Sensory Neuroscience Symposium School of Medicine, UWS Campbelltown Monday 8 December 2014 Poster Session MODULATION OF GANGLION CELL ACTIVITY IN THE MOUSE RETINA BY AN ENDOGENOUS CANNABINOID Ibrahim Darwish University of Sydney [email protected] Ibrahim Darwish, Dario Protti University of Sydney This study addresses long-term questions surrounding the effects of cannabinoids in the mammalian retina using a mouse model. In particular, it aimed to elucidate the effects of an endogenous cannabinoid, anandamide, on the synaptic inputs onto retinal ganglion cells (RGCs). Patch clamp technique was used to obtain direct recordings from RGCs and provide information on current and voltage changes in response to visual and non-visual stimuli. The experiments were designed to expand on current knowledge of the exogenous cannabinoid agonist WIN55212-2, which has been reported to have modulatory effects in the mammalian retina. A series of protocols were designed to determine the effect of anandamide on stimulus-evoked postsynaptic potentials, spike outputs from RGCs, alteration of centre-surround organisation of the receptive field of RGCs and the involvement of cannabinoids in plasticity phenomena. The results confirmed a prominent role of anandamide, and so the cannabinoids, in modulating processing in the mammalian retina. Particularly, anandamide reduced light-evoked excitatory postsynaptic potentials (EPSPs) in RGCs and reduced the suppression index of the receptive field. Interestingly, however, anandamide caused an increase in the spike output of large (A and C type) RGCs, despite the decrease in EPSPs. Anandamide also demonstrated significant involvement in plasticity phenomena, strongly suggesting the presence of a resident endocannabinoid system in the mouse retina.



MOTION-INDUCED LOCALIZATION BIAS IN TOUCH Jack Brooks Neuroscience Research Australia & University of New South Wales [email protected] Jack Brooks1,2, Janet Taylor1,2, Tatjana Seizova-Cajic3 1Neuroscience Research Australia 2University of New South Wales 3Faculty of Health Sciences, University of Sydney Recently a study in humans suggested that motion is an important organizing principle for spatial representations of the skin [1]. Skin representations were conditioned by a moving brush (abridging stimulus). When participants pointed to the brush it was mislocalized by up to 20 mm. It is unknown if such conditioning also results in mislocalization of non-moving stimuli that are independent of the conditioning motion. In 12 subjects, a brush traversed a 20-cm path back and forth along the forearm in three different conditions 1) motion at 15cm/s that was spatially continuous, 2) motion at 15cm/s that did not touch the skin for the middle 10cm of the motion path and 3) motion at 15cm/s that did not touch the skin for the middle 10cm but traversed it at 100cm/s (the abridging condition). The abridging condition was designed to elicit the percept that the two skin patches adjacent to the gap were actually located next to one another. Immediately after or 10 s after every 1-3 brush sweeps, a strong von Frey filament (60g) was applied to the forearm and the subject pointed to where they felt the touch. Localization remained unchanged in the continuous motion condition. In contrast, in both conditions where a patch of skin was not touched by the brush, the von Frey filament was slightly but significantly mislocalized toward the middle of this patch (6.2 ±2.7mm). The mislocalization in these conditions persisted at the 10-s delay (4.9 ±2.9mm), but was not observed in localization judgments after a 1-min break. Thus, relatively small amounts of conditioning resulted in a small mislocalization of position that was robust for a short period after conditioning, but did not appear to cause long lasting changes. The result confirms that representations of skin position are dependent on spatial patterns of motion across the skin. Seizova-Cajic T, Taylor JL (2014) Somatosensory Space Abridged: Rapid Change in Tactile Localization Using a Motion Stimulus. PLoS ONE 9(3): e90892. doi:10.1371/journal.pone.0090892



A PILOT STUDY INVESTIGATING THE RELATIONSHIP BETWEEN TIBIALIS ANTERIOR MUSCLE FASCICLE DYNAMICS AND MUSCLE SPINDLE FIRING PATTERNS James Day University of Queensland [email protected] James Day1, Ingvars Birznieks2,3,4, Vaughan Macefield3,5, Leah Bent6, Heba Khamis3,7, Glen Litchwark1 and Andrew Cresswell1 1Centre for Sensorimotor Performance, University of Queensland 2Physiology, School of Medical Sciences, Faculty of Medicine, University of New South Wales 3Neuroscience Research Australia 4School of Science and Health, University of Western Sydney 5School of Medicine, University of Western Sydney 6Department of Human Health & Nutritional Science, University of Guelph, Canada 7Graduate School of Biomedical Engineering, University of New South Wales, Sydney Muscle spindles are an important source of proprioceptive information. In human studies, spindle recordings are typically interpreted with relation to joint movement and direct measurements of muscle fibre length not monitored. Muscle fibres commonly become decoupled from joint rotations due to the compliance of elastic tissues that lie in series with the muscle. As such, the relationship between muscle fascicle dynamics and spindle firing rate cannot be directly inferred from these studies. The primary aim of this pilot study was to describe the relationship between spindle firing patterns and muscle fascicle dynamics in the tibialis anterior muscle (TA) during passive ankle rotations. Fascicle dynamics were obtained using ultrasonography, which is a non-invasive measurement technique that can be used to visualise muscle fascicles in vivo. Recordings from TA muscle spindle afferents were made using a tungsten microelectrode inserted percutaneously into the common peroneal nerve. Ankle position was moved through plantar flexion and dorsiflexion in a sinusoidal pattern using varying amplitudes and velocities of rotation. Small length changes (<1mm) were accurately measured for TA muscle fascicles, which were slightly out of phase with ankle movements. The onset of spindle firing was closely linked to the onset of muscle fascicle stretch, with peak firing rate (~8-20Hz) closely coinciding with the peak lengthening velocity. Spindle firing rate was higher during the fascicle-lengthening phase compared to the same fascicle lengths during the shortening phase. The results confirm the ability of the TA muscle spindles to sense both fascicle length and velocity changes. The firing patterns were slightly out of phase with joint position suggesting that decoupling of the muscle from joint rotations may have implications for joint position sense. Future research should include tasks or situations where a more compliant muscle-tendon linkage exists, to further understand the implications of muscle fibre decoupling on the spindles ability to sense joint position.



WEBER'S PHENOMENON: A MODEL FOR UNDERSTANDING THERMAL AND TACTILE INTERACTIONS James Dunn University of Western Sydney [email protected] James S Dunn, David A Mahns, Saad S Nagi School of Medicine, University of Western Sydney It has been long observed that a concomitantly cooled stimulus will be perceived as significantly heavier than an identical stimulus of a neutral temperature, this has been termed Weber’s Phenomenon. In this study, the neural substrate of Weber’s phenomenon was investigated to better understand the neural interplay between thermal and tactile systems. In the study paired forces of either 0.5N or 1N (super-imposed on a 1N step) were applied using a 5x5 thermode attached to a mechanical stimulator to the dorsal surface of the hand in the region of ulnar innervation. One of the applied forces had a thermal component, being cooled from 32°C to 28°C, and the other stimuli being thermally neutral (32°C).Subjects reported either the first or second stimulus to be heavier based on a two-alternative forced-choice paradigm. These observations were carried out while all nerve fibres were intact and following compression blockade of the myelinated fibres of the ulnar nerve. Under control conditions all subjects reported the cooled stimulus to be heavier. Subjects performed above chance level (>50%), thus showing evidence of Weber’s phenomenon. Interestingly, the frequency of this effect intensified by >17% (on average) when cold was applied concurrently with the second stimulus rather than the first, thereby indicating an order effect. Following compression blockade of myelinated fibres, the incidence of Weber’s effect was significantly reduced regardless of whether cold was applied concurrently with the first or second stimulus. However, while the effect was reduced to a mere chance level in the case of the former, it remained above chance level for the latter. From the control data it can be confirmed that Weber’s phenomenon is an observable tactile and thermal interaction. The marked reduction in the incidence of Weber’s phenomenon following conduction blockade of the myelinated fibres indicates that it is preferentially mediated by the myelinated neural network.



PROCESSING MULTI-UNIT INFORMATION RECORDED FROM THE MEDIAN NERVE USING AN INTRAFASCICULAR ELECTRODE James Wright The MARCS Institute, University of Western Sydney [email protected] James Wright1, Paul Breen1, Vaughan Macefield1,2, André van Schaik1, Jonathan Tapson1 1Biomedical Engineering and Neuroscience Group, MARCS Institute, University of Western Sydney 2School of Medicine, University of Western Sydney A variety of impairments to the central nervous system can lead to paralysis or paresis while leaving the peripheral nervous system functional. Forces applied to the skin of the fingertips excite cutaneous mechanoreceptors, encoding information utilised in object manipulation. An approach for control of assistive devices or neuroprosthetics that aim to return motor function to the subject is to utilise the intact somatosensory signals as a sensor signal in a closed loop control scheme. Interfacing with the peripheral nervous system using microneurographic techniques allows for the recording of electroneurographic (ENG) signals. In this study an intrafascicular electrode was introduced percutaneously into the median nerve of awake, healthy human subjects. Multi unit recordings were made from a fascicle with cutaneous afferents from the index fingertip. The platform was attached to the shaft of a DC motor under microprocessor control. Ramp-and-hold tangential forces of various amplitudes and ramp rates were delivered. The multi unit afferent activity recorded during the task was processed offline to determine if features related to the stimulus characteristics could be extracted. The features were used to train an extreme learning machine as a classifier of different somatosensory stimuli. In the future the possibility of extracting features and classify stimuli in realtime will be explored.



THE RETINAL ON PATHWAY'S RESPONSE TO THE OFF STIMULUS Josef Esoj Daroczy University of Sydney [email protected] Josef E Daroczy, Dario A Protti, Jin Y Huang Bosch Institute, University of Sydney The retina has a neural pathway which is excited more by an increase in a light stimulus' mean luminance (ON stimulus), which is termed 'the ON pathway'. During a decrease in stimulus mean luminance (OFF stimulus), this ON Retinal Ganglion Cell (ON RGC) in this pathway is inhibited, but exhibits an overshoot in spiking response at stimulus offset. ON RGC response was investigated using a dynamic clamp technique which injected current into the cell to produce changes in membrane conductance. This technique allowed us to record various RGCs’ spiking responses to the input of previous studies’ recorded synaptic inputs onto ON RGCs. With these synaptic inputs we can simulate an ON RGC’s response to various light stimuli. We can also alter the synaptic inputs to isolate the contribution of specific features of the synaptic inputs. By comparing previously-recorded synaptic inputs during ON and OFF stimuli, we determined that circuitry producing this ON RGC overshoot in spiking response is likely to be different to the circuit producing the spiking increase during the ON stimulus. By altering features of synaptic inputs recorded during an OFF stimulus, we found that the increased amplitude of the presynaptic ON Cone Bipolar Cell’s (ON CBC’s) excitatory synaptic input primarily produced the increased spiking response. By recording the ON RGC’s response to synaptic inputs previously recorded during OFF stimulus both with and without infusion of tetrodotoxin, we found that the CBC’s increased excitatory synaptic input at OFF stimulus offset relied upon inhibition of the CBC by a spiking neuron during the OFF stimulus period. These results tell us how the circuitry of the ON pathway responds to an increase in light at the start of the ON stimulus differently to an equivalent increase in light at the end of the OFF stimulus.



CALRETININ EXPRESSION IDENTIFIES TWO FUNCTIONALLY DIFFERENT NEURON POPULATIONS IN MOUSE SUPERFICIAL DORSAL HORN Kelly Smith University of Newcastle [email protected] KM Smith1, JF Madden1, SA Dickinson1, RJ Callister1, DI Hughes2, BA Graham1 1Biomedical Sciences and Pharmacy, University of Newcastle 2Institute of Neuroscience and Psychology, University of Glasgow, United Kingdom Neurons in the spinal cord superficial dorsal horn (SDH) receive and process noxious and innocuous peripheral inputs. One barrier to understanding how these diverse signals are processed in the SDH has been the region's neuronal heterogeneity. A number of neurochemical markers, including the calcium binding protein calretinin, have been employed to dissect the heterogeneity of SDH interneurons and here we use transgenic mice that express enhanced green fluorescent protein (eGFP) in calretinin (CR) positive interneurons to begin characterising this SDH subpopulation. Adult mice (C57Bl/6 background, ~ P80) were anaesthetised (ketamine 100 mg/kg i.p.) and decapitated. Transverse or parasagittal slices were prepared from the lumbar spinal cord and patch-clamp recordings were made from CReGFP-positive neurons in laminae I - II of the SDH. Neurobiotin (0.2%) was included in the internal solution and slices were fixed after recording and processed for morphological analysis. We identified two response profiles in CReGFP-positive neurons: 1) a large population (69/91 neurons) that exhibited A-type potassium currents and received high frequency excitatory drive (17.2 ± 1.2 Hz); and 2) a smaller population (22/91 neurons) that exhibited Ih and T-type calcium currents and received low frequency excitatory drive (0.5 ± 0.2 Hz). Morphological analysis showed neurons that expressed A-currents had morphologies consistent with those described for excitatory interneurons. Neurons expressing Ih and T-type calcium currents, however, had morphologies typical of inhibitory interneurons. Our findings suggest calretinin expression alone is not a faithful marker of excitatory interneurons in the SDH because a significant number exhibit morphological and physiological characteristics of inhibitory interneurons. We propose the two populations play differing roles in SDH function: 1) excitatory CReGFP interneurons are under high levels of background excitatory drive, however they would be difficult to recruit because they express A-type potassium currents that supress AP discharge; 2) inhibitory CReGFP interneurons receive weak excitatory drive, but may be more easily recruited because they express subthreshold currents known to promote AP discharge.



TONIC GLYCINE-MEDIATED INHIBITION REGULATE PARVALBUMIN POSITIVE DORSAL HORN INTERNEURON EXCITABILITY Mark Gradwell University of Newcastle [email protected] MA Gradwell1, RJ Callister1, DI Hughes2, BA Graham1 1Biomedical Sciences and Pharmacy, University of Newcastle 2Institute of Neuroscience and Psychology, University of Glasgow, United Kingdom The dorsal horn of the spinal cord is an important site for modality specific processing of sensory information related to nociception, touch, temperature and itch. Importantly, segregation of these modalities is essential for contextually relevant sensory experience. When modality segregation fails aberrant sensory experiences such as allodynia may emerge. We have recently described a population of inhibitory parvalbumin-positive interneurons (PVINs) with functional properties and connectivity that would enable them to segregate tactile and nociceptive information (Hughes et al, 2012 J Physiol 16:3927). These PVINs receive weak excitatory synaptic input and strong glycinergic inhibitory input. The current set of experiments sought to examine the role of tonic inhibitory currents in PVINs. Targeted patch-clamp recordings were made from transgenic mice that express enhanced green fluorescent protein (eGFP). Adult mice (2-3 months old, both sexes) were deeply anaesthetized with ketamine (100 mg/kg, i.p.) and decapitated. Parasagittal spinal cord slices (200um thick) were prepared from the lumbar cord. Recordings were made with a CsCl-based internal (holding potential -70 mV). Tonic currents were detected in all recordings from PVINs (n = 14), as indicated by a shift to mean holding current during the application of GlyT1 (-57±6 vs -88±8pA) and GlyT2 (-60±5 vs -84±12pA) inhibitors (Org24598 10 µM; Org25543 10 µM). In order to assess the functional relevance of tonic glycine currents we recorded action potential (AP) firing patterns using a KGluc internal and a series of depolarising current injections. Org24598 application decreased AP firing frequency, and induced a shift that favoured an initial bursting discharge. Conversely, strychnine application increased AP firing frequency, and induced a shift that favoured a tonic firing discharge. Together these data suggest tonic glycine-mediated inhibition can modify the output of parvalbumin-positive INs and thus alter the capacity of spinal circuits to process and segregate tactile and nociceptive signals. Hughes, D. I. et al. Morphological, neurochemical and electrophysiological features of parvalbumin-expressing cells: a likely source of axo-axonic inputs in the mouse spinal dorsal horn. The Journal of Physiology 590, 3927–3951 (2012)



E-GROUP (EFFERENT) VESTIBULAR NEURONS SHOW HOMOGENEOUS SYNAPTIC INPUT AND DISCHARGE OUTPUT PROFILES IN VITRO Miranda Matthews Sydney Medical School [email protected] Matthews M1, Wijesinghe R1, Murray A2 Tung V1, Zhang, L1, and Camp AJ1 1Discipline of Biomedical Science, Sydney Medical School, University of Sydney 2Columbia University Our sense of balance is fundamental to our ability to interact with our environment, yet we still know little about the central control of the peripheral balance system. Here we confirm the location, and characterize the properties of e-group (efferent) vestibular nucleus neurons in vitro. Methods: Immunohistochemistry: Transverse serial sections (40 μm) were sliced through the 4-week-old mouse brainstem and labelled with antibodies against CGRP (n = 7), and ChAT (n = 4). Retrograde labelling using fluorogold, injected into the posterior semicircular canal of ChAT-Cre, tdTomato mice was also used to confirm the location of e-group neurons. Electrophysiology: Transverse slices (200 μm) were used to characterize intrinsic action potential and discharge properties of visualized e-group neurons (n = 22) in whole-cell current-clamp mode. Synaptic input profiles of vizualized e-group neurons were assessed in whole cell voltage clamp mode (n = 12). Miniature inhibitory postsynaptic currents and miniature excitatory postsynaptic currents were identified using pharmacological blockade. Results: CGRP and ChAT immuno-positive neurons were identified dorsolateral to the genu of the facial nerve (VII). Spontaneous (n = 9) and non-spontaneous (n = 12) neurons show homogeneous passive membrane properties including Input resistance that differ from neighbouring MVN neurons (p < 0.05). In response to both hyperpolarizing and depolarizing steps all E-group neurons respond with a short bust of high frequency (ISI < 5 ms) AP’s at the cessation of the inhibitory stimulus or the onset of an excitatory stimulus. This burst is superimposed on a (10 ± 2 mV) afterdepolarization (ADP) that is completely abolished by the selective T-type calcium channel blocker (TTA-P2). In contrast to other central vestibular neurons all e-group neurons show mixed excitatory and inhibitory synaptic input profiles. E-group vestibular neurons are homogeneous in their discharge output as well as their synaptic input profiles suggesting that central control of peripheral vestibular structures may be related more to the source of the input these neurons receive.



THE EFFECT OF EXPERIMENTAL NERVE COMPRESSION AND DESENSITISATION OF CAPSAICIN AND MENTHOL RECEPTORS ON DYNAMIC COLD ALLODYNIA IN HUMANS Mohamad Samour University of Western Sydney [email protected] Mohamad S Samour, Saad S Nagi and David A Mahns School of Medicine, University of Western Sydney It is generally agreed that cold allodynia is a consequence of impaired (Aδ-fibre-mediated) central inhibition of C-nociceptive inputs. However, it is also known that C polymodal nociceptors are not activated at innocuous low temperatures. Recently, we demonstrated the contribution of C-tactile fibres to another form of allodynia, namely tactile allodynia. In this study, we investigated whether this, or a related, C-fibre class contributes to cold allodynia. In 26 healthy and 3 chronic pain subjects, a series of normally innocuous, localised, thermal stimuli were applied to the skin overlying a painful tibialis anterior muscle (induced by infusion of hypertonic saline). The effects of thermal stimulation on muscle pain were observed prior to and following compression blockade of myelinated fibres. Furthermore, intradermal capsaicin and menthol were used for desensitisation of TRPV1 and TRPM8 channels respectively. Prior to muscle pain, all thermal stimuli were reported as non-painful regardless of whether myelinated fibres were conducting or not. During muscle pain, dynamic skin cooling (32oC◊20oC) evoked significant and reproducible increases in the overall pain intensity (allodynia). This increase was short-lived and locked to the dynamic phase of cooling, as the pain levels returned to baseline during sustained cooling. Dynamic warming had no effect on pain levels. Cold allodynia persisted following nerve compression, TRPV1 and TRPM8 desensitisation. In clinical subjects, without any pain-producing manipulations, a similar expression of C-fibre-mediated allodynia was observed. In conclusion, cold allodynia includes a non-TRPV1- and non-TRPM8-dependent phenomenon, which is mediated by low-threshold C fibres with a predilection for dynamic cooling.



PERCEPTION OF MULTIPLE ELECTRODE STIMULATION WITH A SUPRACHOROIDAL RETINAL PROSTHESIS Mohit Shivdasani Bionics Institute [email protected] Lisa N Gillespie1,2, Nicholas C Sinclair1, Matthew A Petoe1, Mohit N Shivdasani1,2, Darien Pardinas Diaz1, and Peter J Blamey1,2 1Bionics Institute 2Medical Bionics Department, University of Melbourne Retinal prostheses aim to restore vision to the profoundly vision impaired through electrical stimulation of the retina using implanted electrode arrays. Stimulation from individual electrodes produces a range of visual percepts, known as phosphenes. How effectively these phosphenes can be combined to form complex images depends on their individual characteristics and how they interact. Three patients with retinitis pigmentosa were implanted with a suprachoroidal array consisting of 20 electrodes. Using previously optimised stimulation parameters and threshold levels, experiments were performed in two patients to investigate the effect on perception of multiple electrode and dynamic stimulation. Multiple electrodes corresponding to images of white wedges oriented in four directions on a uniform background of variable grayscale level were stimulated. Patients were asked to identify wedge orientation. Dynamic stimulation experiments utilised a single white bar moving across the electrode array at various speeds, and the patient was asked to indicate which direction the bar was moving. Patient 1 correctly identified wedge orientation with at least 80% accuracy with background intensities between 0 and 50%, which was reduced to a score of 20% at 90% background intensity. Patient 2 performed with up to 75% accuracy when wedge images at full contrast (0% background intensity) were presented; decreasing contrast was not tested. Patient 1 was able to identify direction of motion of a moving bar at speeds of up to 64 degrees per second with an accuracy of at least 80%, and maintained performance at better than chance levels at 80 degrees per second. Patient 2 had more difficulty with this task but his performance reached the pass criterion (62.5%) at a maximum speed of 16 degrees per second. The ability to detect motion and identify objects despite poor contrast demonstrates the capacity of the suprachoroidal device to provide meaningful information to visually impaired patients.



SYNCHRONOUS SPONTANEOUS ACTIVITY IN DIFFERENT LEVELS OF THE AUDITORY SYSTEM Namrata Sobarun University of Western Sydney [email protected] ND Sobarun1, SC Chen2, JW Morley1, CH Parsons1 1School of Medicine, University of Western Sydney 2Department of Physiology, University of Sydney Modification of auditory input results in changes in the auditory system including increased spontaneous activity and increased synchronization of neural activity. These changes occur after noise-induced hearing loss, and have been proposed as a neural mechanism responsible for tinnitus. There has been little attempt to investigate the relationship of synchronous spontaneous activity throughout different levels of the auditory system. Gaining an understanding of how spontaneous activity develops and is propagated throughout nuclei of the auditory system, will increase our understanding of the pathophysiological basis of tinnitus. In this study we unilaterally exposed anesthetized adult Long Evans rats to a 115dB-SPL, 16kHz 1/10th octave bandpass noise for 1-hour. Three months later we recorded extracellular activity in the cochlear nucleus, inferior colliculus and auditory cortex using 32 and 64 channel electrode arrays. Recordings from aged-matched normal hearing animals were used as controls. Baseline spontaneous activity was measured over a period of 10 minutes, followed by a five minutes of exposure to 80 dB SPL white noise. Recording of spontaneous activity was resumed for 20 minutes post-sound stimulus. We expected that the spontaneous activity of a proportion of neurons would be suppressed due to the exposure to the white noise stimulus, and that by further recording spontaneous activity we would gain an insight into the relative re-emergence spontaneous activity of the recorded areas. Following acute, moderate noise exposure, spontaneous activity recorded from control animals was not affected. In contrast in the noise-damaged animals, spontaneous activity measured in auditory cortex and inferior colliculus was significantly increased, while that of the CN was depressed.



PERCEIVED FREQUENCY OF TWO OUT-OF-PHASE VIBRATING PROBES IS AFFECTED BY THE SEPARATION BETWEEN THE PROBES BUT NOT THE SKIN TYPE Robin Andersson Neuroscience Research Australia & Linköping University [email protected] Andersson R1,2, Vickery R3, Birznieks I1,3, MacIntyre S1,4 1Neuroscience Research Australia 2Linköping University 3University of New South Wales 4University of Sydney Natural tactile stimuli evoke responses in individual skin afferents that vary in response latencies and firing rates. The population code will also differ for hairy and glabrous skin sites due to different receptor types and density of their distribution. We investigated how these population responses are integrated into a percept with a psychophysical investigation of the responses to two probes vibrating on the skin. We used a two-interval forced choice protocol, with a standard stimulus of two probes each vibrating at a frequency of 25Hz, 180° out of phase. The comparison stimuli were delivered in phase (24 - 54Hz). Participants (N = 11) judged which stimulus had the highest frequency. Six distances (1 - 16cm) were tested on both the hand and the upper arm. Results: At 1cm separation, the perceived frequency of the out-of-phase 25Hz stimulus was significantly higher than 25Hz (mean = 43.9Hz, t21 = 17.2, p < 0.001). The strength of this effect decreased with increasing separation of the probes (F1,10 = 182.8, p < 0.001). The same trends were seen on both the palmar skin of the hand and the hairy skin of the upper arm, and the sites did not significantly differ (F1,10 = 3.6, p = 0.087), nor was there any significant interaction between site and distance (F5,50 = 0.7, p = 0.593). The nervous system is able to combine punctate vibratory skin stimuli that differ in their relative phase. The separation of the two probes affects this frequency integration, with phase differences mattering less at greater separations. We also demonstrated that this integration of vibrotactile stimuli operates consistently across body sites despite the marked differences in receptor types, receptive field sizes and spatial acuity for the glabrous skin in the hand and the hairy skin of the upper arm.



VISUALIZING HEARING: IN VIVO AUDITORY TRACT MAPPING IN RATS WITH MANGANESE-ENHANCED MRI Shahad Judi University of Western Sydney [email protected] Shahad Judi1, William S Price1, Timothy Stait-Gardner1, Carl H. Parsons2 1School of Science & Health, University of Western Sydney 1School of Medicine, University of Western Sydney There is an increased interest in the use of manganese-enhanced magnetic resonance imaging (MEMRI) to identify neural activity and architecture in animal models. The paramagnetic property of the manganese ion (Mn2+) results in improved T1-weighted tissue contrast. Its chemical similarity to calcium leads to accumulation of Mn2+ in an activity-dependent manner in excited neurons and thus allows visualization of neuronal activity in vivo and in fixed tissue. Here we present a method to trace regions of sound evoked activity in anaesthetised rats and construct a three-dimensional (3-D) representation of connectivity patterns in the rat auditory system. Long-Evans rats were anaesthetized with a mixture of ketamine and xylazine and placed in a dimly lit sound-attenuating chamber. Auditory brainstem response audiograms were performed to ensure that all animals in the study had normal hearing. Following the ABR, rats received an intraperitoneal (IP) injection of MnCl2 (98 mg/kg). While still under anaesthesia, they were unilaterally (left ear) exposed to 50 ms broadband noise pips (at a rate of 50 Hz). Stimulation was maintained for 6-8 hours. Depth of anaesthesia was monitored and further anaesthetic doses were administered as required to maintain the animals under light anaesthesia. Immediately after sound stimulation, the animals were transcardially perfused with 10 ml 0.9% saline, followed by 4% paraformaldehyde. The brain was removed and stored in PFA overnight before being embedded in agarose gel to stabilize the brain during the MRI procedure. MRI was performed using a high-resolution wide bore Bruker Avance 11.7 T MR spectrometer. To assess of anatomic localization with the accumulated Mn2+ signal enhancement, the MRI data was registered with a stereotaxic rat brain atlas. Strong signal enhancement was observed in most auditory brainstem nuclei using a dose of 98 mg/kg MnCl2, injected IP. This concluded that anterograde MnCl2/MRI tracing allows rapid analysis of topographic organization across multiple brain regions. The method allows a higher data throughput for 3-D studies of large-scale brain connectivity than conventional methods based on tissue sectioning.



AUTONOMIC AND COGNITIVE SIGNATURES OF CYBERSICKNESS Simon Davis University of Newcastle [email protected] Simon Davis, Keith Nesbitt, Karen Blackmore, Eugene Nalivaiko School of Design Communication and IT & School of Biomedical Sciences and Pharmacy, University of Newcastle Cybersickness is a subtype of motion sickness elicited by provocative visual stimulation. Symptoms of cybersickness have been reported during navigation in a computer-generated virtual environment (1), but have never been documented during usage of virtual reality head-mounted displays (VR-HMD) equipped with accelerometers and motion sensors. We thus assessed nausea rating, reaction time, cutaneous (finger) temperature (T) and heart rate (HR) in 26 university students subjected to 15-min simulated ride on a rollercoaster. Subjects weared the Oculus Rift VR-HMD and experienced two version of VR ride (one from Parrot, another from Helix; n=13 each). All subjects experienced vection. Nausea score (max. 10) was higher for the Helix version (6.1±0.4) compared to the Parrot (3.7±0.8), and 83% of Helix rider requested early termination of the experiment vs. 33% of Parrot riders. VR exposure caused prolongation of the simple reaction time (Deary-Lievald test) from 423±4 to 450±9 ms; this increase significantly correlated with the nausea rating at the end of ride. HR did not change in 11/26 subjects or raised by 7-33 bpm in the remainder. Effects on the finger temperature was complex and depended on the basal values of this variable. In 7/8 subjects whose finger T was low (23-29°C), VR provocation caused substantial warming (>4°C). Responses in high-T group whose basal values were 32-35°C were more variable: substantial rise in 2/17; biphasic (small fall/rise) in 8/17 and no effect in 6/17; one subject had large fall. We conclude that: i) VR-HMD are capable of producing cybersickness, with quite high incidence depending on visual context; ii) VR-HMD-induced cybersickness may adversely affect human performance; and iii) finger warming associated with cibersickness indicates skin vasodilation, and is in accord with our recently proposed concept of the central role of thermoregulatory disturbances in nausea (2). Kim et al. Psychophysiol. 2005, 42:616-25 2. Nalivaiko et al., Temperature, in press



EXTENDING THE VIABILITY OF ACUTE BRAIN SLICES Yossi Buskila The MARCS Institute, University of Western Sydney [email protected] Yossi Buskila1, Paul Breen1, JonathanTapson1, André Van-Schaik1, Matthew Barton 2, John Morley2 1The MARCS institute, University of Western Sydney 2School of Medicine, University of Western Sydney The lifespan of an acute brain slice is approximately 6–12 hours, limiting potential experimentation time. We have designed a new recovery incubation system capable of extending their lifespan to more than 36 hours. This system controls the temperature of the incubated artificial cerebral spinal fluid (aCSF) while continuously passing the fluid through a UVC filtration system and simultaneously monitoring temperature and pH. The combination of controlled temperature and UVC filtering maintains bacteria levels in the lag phase and leads to the dramatic extension of the brain slice lifespan. Brain slice viability was validated through electrophysiological recordings as well as live/dead cell assays. This system benefits researchers by monitoring incubation conditions and standardizing this artificial environment. It further provides viable tissue for two experimental days, reducing the time spent preparing brain slices and the number of animals required for research Buskila Y, Breen PP, Tapson J, Van-Schaik A, Barton M and Morley J (2014) Extending the viability of acute brain slices. Sci.Rep. 4, 5309; DOI:10.1038/srep05309


uws sensory neuroscience symposium 2014 · 9:00 – 10:00 keynote lecture chair: carl parsons...

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