437

Emma L. Lane and Stephen B. Dunnett (eds.), Animal Models of Movement Disorders: Volume I, Neuromethods, vol. 61,DOI 10.1007/978-1-61779-298-4, © Springer Science+Business Media, LLC 2011

Index

A

Abnormal involuntary movements (AIMs). See L-DOPA induced dyskinesia

ADC. See Apparent diffusion coefficientAIF. See Arterial input functionAllatostatin receptor (AlstR) ......................................... 227Alpha-synuclein

C. elegans ..........................................................36, 45–47DA neuron analysis ................................................... 46degenerating neurons ................................................. 47dose-dependent neurodegeneration ........................... 46Parkinson’s disease ..........................................6, 25, 244animal model ......................................47, 321, 326, 330

Amphetamine rotation. See Rotation, amphetamineAmytrophic Lateral Sclerosis. See Volume II

(Neuromethods 62)Anaesthesia

fMRI, rodents .......................................................... 146MRI experiment

a-chloralose and medetomidine ................ 136–137halothane ........................................................... 136

Animal fixation .............................................................. 137Apomorphine rotation.

See Rotation, apomorphineApparent diffusion coefficient (ADC)

maps ................................................................ 139, 140representative time course ................................ 139, 140thresholds, ischemic core and penumbra ......... 138–139

Arterial input function (AIF)definition ................................................................. 167PET

description ......................................................... 167less-invasive method .......................................... 167TAC and image-derived .................................... 167

B

Balance beam testbalance and motor coordination ................................ 79materials and methods ......... 80–82, 118–119, 287–288,

328–329mouse ........................... 80–83, 118–119, 287–288, 329rat ................................................................... 328–329

Basal ganglia. See also Volume II (Neuromethods 62)BAC transgenic mice ............................................... 197dendritic calcium imaging ............................... 202–207intensive treadmill exercise ...................................... 360IR-DIC optics ......................................................... 196MPTP-lesioning ..................................................... 356nonlinear fluorescence microscopy

confocal pinhole aperture ................................... 192high-resolution optical study ............................. 192patch-clamp techniques ..................................... 191photo-stimulation and photolysis .............. 195–1962PLSM .............................................................. 192system components .................................... 192–195

optical voltage measurementsFRET mechanism ............................................. 216mammalian neurons........................................... 215Purkinje neurons ................................................ 215strengths and limitations.................................... 215

optogenetic approachesaxons and synaptic terminals.............................. 214ChR2 ................................................................ 213circuit analysis .................................................... 213coherent (laser) light source ............................... 214corticostriatal and thalamostriatal

microcircuits ........................................ 213–214dendritic topography .......................................... 214hyperpolarization ............................................... 2132 photon microscopy .......................................... 215somatic patch electrode ...................................... 214

organelle imaging, neurons .............................. 210–212patch-clamp experiment .......................................... 1962PLU ............................................................... 208–209SPNs ................................................................ 196–202

Behavioral phenotyping ..................................................... 4Behavioural testing, rodent. See also Volume II

(Neuromethods 62)exercise paradigms

Fast-Trac running wheel .................................... 359intensive treadmill exercise ................................ 3606-lane treadmill apparatus ................................. 359running incentive ....................................... 359–360

motor behavioraccelerating rotarod ............................................ 360

438 AnimAl models of movement disorders: volume i

Index

Behavioural testing, rodent (continued)corridor test ....................................................... 289cylinder test ................................288–289, 327–328ladder ......................................................... 119–120ledged beam test ........................................ 328–329limb-use asymmetry................................... 327–328mid-field crossings and time spent ............ 360–361motorized treadmill ........................................... 360rotation (see Rotation)vibrissae-elicited limb placing .................... 330–331

non-motor behaviorcognitive function and mood disorders .............. 361elevated plus maze ..................................... 361–362object recognition task ............................... 126–128sensory stimuli ................................................... 330stimulus contact and removal ............................. 330sucrose preference test ....................................... 361tactile stimulation test .......................................... 32

BAC transgenic mice ..................................................... 197

C

Caenorhabditis elegans modelsbehaviors .................................................................... 33definition ................................................................... 32genome and shares ..................................................... 33human movement disorders ....................................... 33large-scale RNAi screening ................................. 40–42nervous system

anatomy and complete connectivity ..................... 34anterior deirid neurons (ADEs) ........................... 34basal slowing response ......................................... 36DA neurons ................................................... 34–35mammalian neuronal function ............................. 34

online resources ......................................................... 32Parkinson’s disease

LRRK2 and PINK1 ............................................ 36orthologs and mutants ................................... 36–37susceptibility genes .............................36–38, 43–44therapeutic targets and chemicals .................. 38–39

6-OHDA-induced dopaminergic toxicity ........... 44–45reverse genetic screens ............................................... 33RNAi, neuronal cells............................................ 47–50a-syn proteotoxicity ............................................ 45–47959 somatic cells ........................................................ 32

Carbon–11, radiochemistryprimary precursor

description ................................................. 157–158methane ............................................................. 158

14 N(p, a) 11C nuclear reaction .............................. 156reaction types ............................................. 156, 157

Cat–2 gene ...................................................................... 45Cerebellar and brain stem systems. See Volume II

(Neuromethods 62)Channelrhodopsin–2 (ChR2)

activation ................................................................. 215

advantages................................................................ 214brain slices ............................................................... 228description ............................................................... 213functional synaptic inputs ........................................ 214presynaptic terminals ............................................... 214

Common marmoset. See MPTP-treated primate, common marmoset

Conditioningassociative conditioning ........................................... 313classical (see volume II (Neuromethods 62))6-OHDA lesioned rat ..................................... 313, 339operant conditioning ............................................... 313

Corridor test .................................................................. 289Cylinder test

paw preference ......................................................... 288rat protocol .......................................289, 327–328, 331mouse protocol .................................288, 327–328, 331dopamine depletion ................................................. 327stroke ............... 328 (see volume II (Neuromethods 62))

D

Danio rerio. See ZebrafishDendritic calcium imaging

calcium dye selection ....................................... 203–204direct patch clamping .............................................. 202line scans .......................................................... 204–207neurons .................................................................... 207voltage-dependent channels..................................... 202

Dendritic spinesdensity determination, biocytin-HCl ...................... 365recording electrodes ................................................. 363

Diffusion tensor imaging (DTI)fibre tracking ................................................... 142–143myelinated fibre bundles .......................................... 142

Dopamine (DA)active drugs

amphetamine ............................................. 269–270apomorphine ...................................................... 270

dopamine transporter (DAT) .................................. 356fast-scan cyclic voltammetry ............................ 365–366lesion

6-OHDA ........................................267–9, 281–283MPTP ........................................353, 371–373, 401

neuronsCaenorhabditis elegans ............................................34cellular aspects ..................................................... 35dose-dependent degeneration .............................. 43human a–syn ....................................................... 39neurodegeneration ............................................... 43normal and degenerative states ............................ 35a-synuclein proteotoxicity ............................. 45–47

Drosophilaanti-Parkinson drugs ................................................. 63behavioural activity

geotaxis assay ................................................. 59–60

AnimAl models of movement disorders: volume i 439

Index

locomotor assay .............................................. 59, 61phototaxis assay ............................................. 59, 61sensory function ............................................. 55–56random locomotor activities, Canton-S

and stocks ...................................................... 56Canton-S flies, UAS transgene ............................ 60–62human coding gene.................................................... 56in vitro assays

dot blot analysis ................................................... 60immunoblot assays ............................................... 58western blot assays ......................................... 58–59

maintenance, stock cultures and experimental flies .......................................... 60

media preparationprocedure ....................................................... 56, 58recipe ............................................................. 56, 57

a–synuclein ............................................................... 62DTI. See Diffusion tensor imagingDyskinesia. See L-dopa-induced dyskinesia

E

Electrophysiological effectselectrotonic potentials and dye-coupling ................. 226HD and PD ............................................................. 228ionic currents ........................................................... 230optogenetics ..................................................... 227–228passive membrane properties ................................... 228patch-clamp

and optical imaging techniques ................. 226–227recordings .................................................. 225–226

preparationsacute brain slices ................................................ 222acutely dissociated neurons ................................ 223in vivo recordings ....................................... 223, 224neuronal cultures and networks ................. 222–224selective neuronal ablation ................................. 227sharp electrode recordings ................................. 225

synaptic activity ............................................... 230–235Elevated beam test. See Balance beam testEPSCs. See Excitatory postsynaptic currentsEshkol-Wachmann movement notation (EWMN)

limb ........................................................................... 96movement elements ............................................. 95–96

Ethological ratings ........................................................ 402European Mouse Disease Clinic

(EUMODIC) ........................................... 111–112European Mouse Phenotyping Resource

of Standardised Screens, (EMPReSS) ................. 67European Union Mouse Research

for Public Health and Industrial Applications (EUMORPHIA) ......................... 111

EWMN. See Eshkol-Wachmann movement notationExcitatory postsynaptic currents (EPSCs)

amplitude and frequency.......................................... 364changes, amplitude and frequency ........................... 364

MSSNs .................................................................... 234physiological readouts and properties ...................... 362pyramidal neurons ................................................... 231

Exercisemotorized treadmill ................................................. 360paradigms

Fast-Trac running wheel .................................... 359intensive treadmill exercise ................................ 3606-lane treadmill apparatus ................................. 359running incentive ....................................... 359–360

repair processes, striatum and motor learning .......... 358

F

Fast-scan cyclic voltammetrychanges, extracellular dopamine............................... 366coronal corticostriatal slices ............................. 365–366electrical stimulation ................................................ 366

fcMRI. See Functional connectivity MRIFibre tracking

DTI ......................................................................... 142thalamo-cortical connectivity, changes .................... 142

Fluorine–18, radiochemistryvs. carbon–11 ........................................................... 158description, reaction types ....................................... 158electrophilic radiofluorination ......................... 158–159nucleophilic radiofluorination

aliphatic fluorination, indirect ............................ 160aliphatic substitution, direct ............................... 159aromatic fluorination, indirect ................... 160–161fluorination, direct ..................................... 159–160prosthetic groups ............................................... 161structure, direct and indirect ...................... 159, 160

Forepaw stimulation .............................................. 143, 144protocol

a2-adrenoreceptor ............................................. 143a–chloralose ...................................................... 143

SSEPs signals .................................................. 143, 144therapeutic effect, stem cell ...................................... 145

Functional assessment, neuroplasticity. See also Motor behaviour, rodent

AMPA receptor frequency ....................................... 364amplitude and electrophysiology studies

and biocytin labelingbiocytin injection, MSNs ........................................... 36current-voltage relationship (I-V) curve .................. 364mediated synaptic responses ............................ 364–365MSNs and EPSCs ................................................... 362paired-pulse ratio (PPR) .......................................... 364preparation, brain and coronal

corticostriatal slices ............................................ 362rectangular current pulses ........................................ 364series resistance (Rs) ................................................ 363spermine concentration ........................................... 363voltage clamp and electrical stimulation

methods ............................................................. 363

440 AnimAl models of movement disorders: volume i

Index

Functional connectivitybrain networks

fcMRI ................................................................ 143rs-fMRI ..................................................... 142–143

tracingaxonal ................................................................. 141fibre.................................................................... 142

G

Gait analysis. See also footprint and gait analysismethod ................................................. 77–78,115–117pitfalls ...................................................77–78, 117–118rationale ........................................................... 112, 115

digital systems ...................................................... 76runways .........................................................76, 77, 112video imaging ............................................................ 78

Geotaxis assay ............................................................ 59–60German mouse clinic (GMC) ....................................... 109

Web pages ............................................................... 111Grip strength test .................................................. 123–124GMC. See German mouse clinic

H

Handedness ................................................................... 317Hand shaping movement .......................................... 98–99

rating scale ................................................................. 98transitions ............................................................ 98–99

HD. See Huntington’s diseaseHigh-performance liquid chromatography (HPLC)

gold standard method .............................................. 168radiosynthesis .......................................................... 155ultra-high PLC ........................................................ 168

High-throughput mouse phenotypingcomprehensive analysis approach ............................. 110EUMORPHIA and d EUMODIC ................ 111–112GMC (See German mouse clinic)IMPC ...................................................................... 112large-scale systematic mutagenesis .......................... 109

HPLC. See High-performance liquid chromatographyHuntington’s disease (HD)

chorea treatment ...................................................... 234electrophysiological outcomes .................................. 229motor function ......................................................... 232mouse models .......................................79–83, 228, 231

and Volume II (Neuromethods 62)neuron loss ............................................................... 221

and Volume II (Neuromethods 62)pathogenesis ............................................................ 234

and Volume II (Neuromethods 62)synaptic plasticity ..................................................... 233

6-Hydroxydopamine (6-OHDA)advantages................................................................ 282amphetamine ............................269–270, 309–310, 312

methamphetamine ............................................. 275apomorphine............................................................ 270

conditioningassociative conditioning ..................................... 313operant conditioning.......................................... 313

C. elegans .............................................................. 44–45dopaminergic toxicity .......................................... 44–45dopamine receptors and postsynaptic

signaling............................................................. 301general surgical procedure

cannula and tubing .....................271, 273–274, 283hydrobromide salt and ascorbic acid .................. 269inhalation, neurotoxin ................................ 270–271post-operative care ..................................... 276, 285ten-microlitre microsyringe setup .......271, 273–274surgery considerationsrats ......................................................290–291, 312mice ................................................................... 284

gene expression and receptor binding .............. 307–308lesion

MFB ........................... 267–268, 272–273, 277, 306striatal ........................................................ 273–275nigral .................................................................. 276

mice ................................................................. 281–296motor behaviour

automated freely moving systems .............. 305–306elevated beam .................................................... 293cylinder test ........................288–289, 327–328, 331rotation (see also Rotation)spontaneous turning .......................................... 307drug-induced rotation ........................269–270, 285,

309–310, 312manual observation ............................................ 300rotometer ............................................275, 301–305recording rotational behavior ............................. 286motor and sensory motor deficits .............. 287–290torsional and postural biases .............................. 307rotarod test ........ 71–75, 122–123, 289–90, 294, 360staircase test ........................276, 288–289, 293–294motorized treadmill ........................................... 360

neurotoxic effects ............................................... 44, 267non-motor behavior

cognitive function and mood disorders .............. 361elevated plus maze ..................................... 361–362sucrose preference test ....................................... 361object recognition task ............................... 126–128

post-mortem assessment/group allocations .................................................. 276, 311

postsynaptic activation ............................................. 311rats ............................................ 267, 299, 317–318, 325SHSY5Y cells ............................................................ 38video recording ........................................................ 275

I

Imagingcalcium imaging (See Calcium imaging)DTI (See Diffusion tensor imaging)

AnimAl models of movement disorders: volume i 441

Index

light and EM imaging Volume II (Neuromethods 62)MRI (See Magnetic resonance imaging

and Volume II (Neuromethods 62))PET (See Positron emission tomography)SPECT (See Single positron emission

computed tomography)Immunoblot assays .......................................................... 58International Mouse Phenotyping Consortium

(IMPC) ............................................................. 112IR-DIC optics ............................................................... 196

K

Knockout. See also Tamoxifen, inducible gene knockout

disease-associated alleles .......................................... 246gene inactivation ...................................................... 246protein expression .................................................... 245targeting vectors ...................................................... 256

Kruskal-Wallis non-parametric analysis of variance ........ 71

L

L-dopa-induced dyskinesiaAIMs/dyskinetic movements

AIM subtype ..................................................... 344amplitude scale ............................................ 42–344basic rating scale ........................................ 341–342rating scales, training ......................................... 348

data analysisANOVA ............................................................ 345dyskinesia ........................................................... 424non-parametric statistics ............................ 344–345theoretical maxima ..................................... 348–349

experimental designAIMs ................................................................. 338chronic treatment period ........................... 338–339putative anti-dyskinetic agents .................. 338, 3406-OHDA lesion types and treatment

groups ...........................................344, 346–347methodology .............................................. 340–341strain and species ............................................... 345testing environment ................................... 347–348

L-dopaadministration route .......................................... 348anti-Parkinson’s effect ................................ 421, 422behavioral activation .......................................... 345benserazide dosage ............................................. 347

MPTP-treated primateAfrican Green Monkey ..................................... 424common marmosetdyskinesia protocols ............................384, 387, 392drug testing .........................................391, 393–394dyskinesia rating scales .............................. 379–382primate species ................................................... 378

Ladder ................................................................... 119–120Learned nonuse ..................................................91, 92, 103

Limb-use asymmetry. See Cylinder testLocomotion ............................................................... 20, 23Locomotor

activity and motor disabilityautomated test units ........................................... 386DasyLab acquisition software ............................ 386rating scale ......................................................... 386statistical significance, power analysis ................ 386

larval and adult zebrafishanxiolytic effect, drugs ......................................... 20functions .............................................................. 19place preference behaviour ............................. 19–20video tracking ...................................................... 19well plates ............................................................ 19

Long-term depression (LTD)........................225, 229, 232, 233, 270

Long-term potentiation (LTP) ...................................... 225

M

Magnetic resonance imaging (MRI)description ....................................................... 135–136neurological damage, rats and mice

anaesthesia ..........................................136–137, 146animal fixation ................................................... 137functional activation and connectivity ....... 141–145movement artefacts .................................... 145–146shine-through effect .......................................... 146structural damage ....................................... 138–141

physical variables and in vivo imaging ............. 137–138RF signals ................................................................ 136

Mann-Whitney U–test .................................................... 71MAO genes. See Monoamine oxidase genesMCAO (middle cerebral artery occlusion) .......140, 144, 326

and Volume II (Neuromethods 62)Median forebrain bundle (MFB)

intracerebral injection .............................................. 268lesion coordinates .................................................... 277ten-microlitre microsyringe setup ............................ 271unilateral lesion ................................................ 272–273

Medium spiny neurons (MSNs)biocytin injection ..................................................... 365physiological properties ........................................... 362whole-cell recordings ............................................... 363

MFB. See Median forebrain bundle1-Methyl–4-phenyl–1,2,3,6-tetrahydropyridine.

See also MPTP-treated mouse, primateselective neurotoxin ......................................... 366–367safety issues .......................................354–355, 383, 388mouse (see MPTP-treated mouse)primate (see MPTP-treated primate)zebrafish larvae

cell death ........................................................ 21, 22neurotransmitter levels ......................................... 22

Monoamine oxidase (MAO) genesactivity ....................................................................... 22

442 AnimAl models of movement disorders: volume i

Index

Mouse. See also 6-Hydroxydopamine; MPTP-treated mouse

balance beam/elevated bridge test (see Balance beam test)

footprint test and gait analysis ............................. 76–79high-throughput phenotyping (see High-throughput

mouse phenotyping)ES cells .................................................................... 245glutamate receptor function ..................................... 233Huntington’s disease ................................................ 231intranigral grafted cells ............................................ 235mammalian gene function ....................................... 248PD-associated alleles ............................................... 245operational sensitivity ................................................ 66R6/2 ......................................................................... 230rotarod test (see Rotarod test)SHIRPA (see SHIRPA screen test)

MPTP-treated mousedegree of lesion ................................................ 357–358lesion regimen .................................................. 358–359motor behavior .....................65–86, 325–336, 353–370neuroplasticity ................................................. 355–367neurotransmitter concentrations .............................. 357nigrostriatal dopaminergic neurons ................. 357–358non-motor behavior ......................................... 361–362parameters, lesioning regimen ................................. 357preparation and injections ........................................ 355species, age and sex selection ........................... 355–356stained ventral mesencephalon section .................... 358western immune-blotting ........................................ 358

MPTP-treated primateAfrican Green Monkey

advantages and disadvantages ............................ 425controlling observer bias ............................ 410–411dyskinesia ........................................................... 424dosage differences ...................................... 416–418eyeblink rate measurements ............................... 424intoxication ................................................ 401–402Healthy Behavior scores .................................... 415low, mid and high ...................................... 413–417Parkinsonism ..................................................... 418Parkscore .................................................... 413–414Parkscore vs. Healthy Behaviors .........413–418, 422

behavioural effects ............................379–380, 385–386common marmoset

advantages .......................................................... 384behavioural deficits .....................379–380, 385–386care regimes ....................................................... 385dyskinesia ........................................................... 387

(see also L-dopa-induced dyskinesia)health effects .............................................. 388–390laboratory comparisons .............................. 391–392MPTP administration protocols.........383, 388, 392neuroprotection and resoration .................. 394–395rating scales ................................................ 378–383

cynomologous monkey .............................374–375, 380MPTP-protocols .............. 375, 383–384, 388, 392, 411protocols and rating scales

MPTP administration ....................................... 411sample size ................................................. 409–410variability, dosesoutcome and recovery ........................................ 414motor and behavioral function ............403–406, 412videotaped assessment ............................... 424–425

rating scales of motor performance ................................378–383, 410–415

rhesus monkey ..........................................374–375, 380squirrel monkey ............................................... 375, 379vervet monkey...........................................374–375, 380

MRI. See Magnetic resonance imagingMSNs. See Medium spiny neuronsMultiple Systems Atrophy (MSA). See Volume II

(Neuromethods 62)

N

NeurodegenerationC. elegans .................................................................... 43DA ............................................................................. 396-OHDA................................................................... 44PD susceptibility genes ........................................ 43–47

Neuroinflammation, PETdose-dependent displacement .................................. 185TSPO .............................................................. 184–185

Neurological evaluation, mice movement disordersbalance beam/elevated bridge test ........................ 79–83footprint test and gait analysis ............................. 76–79rotarod ................................................................. 71–75SHIRPA screen ................................................... 67–71

Neuroplasticityfunctional assessment

biocytin injection, MSNs ................................... 365electrophysiology studies

and biocytin labeling ............................ 362–365exercise paradigms ..................................... 359–360fast-scan cyclic voltammetry ...................... 365–366

Neurotransmitter systems, zebrafish brainMAO genes ......................................................... 15–16Receptors ................................................................... 15tyrosine hydroxylase (TH) ......................................... 15

Non-motor symptoms ................................................... 112

O

Object recognition task ......................................... 126–128Ocularmotor systems. See Volume II (Neuromethods 62)6-OHDA. See 6-HydroxydopamineOpen field test ....................................................... 113–115Open reading frame (ORF), 247Optogenetic approaches

axons and synaptic terminals ................................... 214ChR2 ....................................................................... 213

AnimAl models of movement disorders: volume i 443

Index

circuit analysis .......................................................... 213coherent (laser) light source ..................................... 214corticostriatal and thalamostriatal

microcircuits .............................................. 213–214dendritic topography ............................................... 2142P microscopy ......................................................... 215somatic patch electrode ............................................ 214

Organelle imaging, neuronsdye loading .............................................................. 210high-quality measurements ...................................... 211membrane permeable cationic dyes ......................... 210mitochondrial redox state ................................ 212–213mito-roGFP probe .................................................. 212Parkinson’s disease ................................................... 210redox status .............................................................. 212regions of interest (ROIs) ........................................ 211SNc dopaminergic neurons ...................................... 211TMRM fluorescence intensity ................................ 211ventral tegmental area (VTA) .................................. 212

P

Parkinson’s disease (PD)animal models .......................................................... 232behavioural tests

apomorphine .............................................. 319–320drug-induced rotation (See Rotation)L-DOPA ........................................................... 325ledged beam test ........................................ 328–329limb-use asymmetry................................... 327–328somatosensory asymmetries sensory

stimuli .......................................................... 330stimulus contact and removal ............................. 330tactile stimulation test ........................................ 329vibrissae-elicited limb placing .................... 330–331

C. elegans .............................................................. 31–54description ....................................................... 243–244DJ-1 .................................. 23–24, 37, 38, 127, 326, 330drosophila .............................................................. 55–64dyskinesia (See also L-dopa induced

dyskinesia (LID))endogenous proteins ................................................ 248gain-of-function ...................................................... 246gene inactivation .......................................245–246, 248genetic mouse models

CreERT2 transgenic mice ........................... 259–262cell types and tissues .......................................... 259EUCOMM-Tools programme .......................... 259inducible Cre activity ......................................... 250lymphoma cells .................................................. 262transgenic mouse lines ................228, 245, 259–260transgenic a –synuclein ................................. 58–59protocol .............................................................. 262reporter mice .............................................. 260–261Rosa26 locus ...................................................... 260ZFNs ................................................................. 249

genetic mutationsconditional gene targeting vectors ............. 256–258inducible expression vector cloning.................... 251b-galactosidase reporter cassette ................ 253–254large-scale mutagenesis programmes ......... 254–256missense mutation ............................................. 244ORF-coded protein ........................................... 250plasmids ............................................................. 249potential duplication .......................................... 254primers ....................................................... 249–250RMCE positive ES cell clones .......................... 253Rosa26 locus ............................................... 250–253somatic cells ............................................... 253–254a-syn proteotoxicity ....................................... 45–47tamoxifen inducible gene expression cells .......... 249tamoxifen inducible gene knockout ........... 253–259targeting vector generation ................................ 259therapeutic targets and chemicals .................. 38–39transgene activation ................................... 246–247

human movement studiesbasal ganglia ....................................................... 320motor system ..................................................... 320parkinsonian patients ......................................... 321skilled movements ............................................. 321UPDRS ..................................................... 409, 423

MPTP (See 1-methyl–4-phenyl–1,2,3,6-tetrahydropyridine (MPTP))

MPTP-treated mouse (See MPTP treated mouse)MPTP-treated primate (See MPTP-treated primate)neurotoxic vs. genetic models................................... 231neuron loss ....................................................... 228, 317nigrostriatal dopaminergic neuron ........................... 326non-neuronal cell types, brain .................................. 2456-OHDA-treated mouse (See 6-Hydroxydopamine)6-OHDA-treated rat See (6-Hydroxydopamine)PET (See also Positron emission tomography)

AAV5-TH ......................................................... 184dopamine neurotransmission system ................. 183ligand role .......................................................... 184met-amphetamine ............................................. 184pre-synaptic neuron ........................................... 183radioligands selective targets .............................. 183

susceptibility genesLRRK2 and PINK1 ............................................ 36a-synculein .......................................................... 55

Zebrafish (See Zebrafish)Partial lesion models of movement disorders ................. 6–8Patch-clamp recordings

cell attached configuration ....................................... 226description ............................................................... 225infrared (IR) videomicroscopy ......................... 225–226

PET. See Positron emission tomographyPhototaxis assay ............................................................... 59PINK1 .............................................. 15, 23–25, 36–38, 3262PLSM. See Two-photon laser scanning microscopy

444 AnimAl models of movement disorders: volume i

Index

2PLU caging molecules ................................................. 209EPSP and calcium transient .................................... 208galvanometer mirrors ............................................... 209glutamatergic synaptic inputs .................................. 208glutamate uncaging .................................................. 210large-scale bath application ..................................... 208photodamage ........................................................... 209

Pockels cell modulator ................................................... 209Positron emission tomography (PET)

AIFdescription ......................................................... 167advantages .......................................................... 167

animal handlinganaesthesia protocol ................................... 169–172

annihilation eventscircular set-up .................................................... 162detection 511 keV photons ................................ 162line of response (LOR) .............................. 162–163scattered and random coincidence ............. 163–164

attenuation correctionfraction, photons ................................................ 164methods ..................................................... 164–165

biological applicationsassessing brain diseases in vivo ................... 183–185receptor-ligand interaction ........................ 181–183

contribution ............................................................. 152data acquisition and camera ............................. 168–169data processing

first-level analyses ...................................... 177–178injected activity and radioligand mass ................ 178volume of interests (VOIs) ........................ 177–178

image registrationanatomical data .......................................... 176–177co-registration, Brainvisa/Anatomist

software................................................ 169, 176MRI brain atlases .............................................. 177radiotracer-specific PET templates ................... 177registration software .......................................... 176

metabolites and radiopharmaceuticals detectiondescription ......................................................... 167gamma counter .................................................. 168HPLC ............................................................... 168UHPLC, TLC and SPE.................................... 168

pharmacokinetic modellingabsolute vs. biological quantification.................. 178arterial plasma concentration ..................... 179–180case-by-case analysis ......................................... 181graphical methods ...................................... 180–181multi-injection approach........................... 179–180non-metabolized radiotracer .............................. 179rate equations, compartments ............................ 178simplified and reference tissue models .............. 180

physicsemission 511, keV photons ................................ 161isotope, mean distance ........................155, 161–162

positron annihilation .......................................... 161radiochemistry

radionuclides production ........................... 154–155radiosynthesis ............................................ 155–156radiotracer properties ................................. 153–154reaction schemes ........................................ 156–161

radioisotope production ........................................... 168receptor-ligand interaction

benzodiazepine receptor ligand.................. 181–182dose-dependent displacement .................... 181–182in vivo characterisation ...................................... 181positive linear correlations, agonists ........... 182–183

scannerscommercially available PET ...................... 165, 166generations ......................................................... 165SIEMENS Concorde 220 microPET ....... 175–176technological developments ............................... 1757 tesla Varian MRI scanner ....................... 175–176radiotracer-specific PET templates ................... 177

single-photon external source/CT ........................... 170structure, entire process ........................................... 169time-activity curve (TAC)

measured input function .................................... 167pharmacokinetic compartmental modeling ........ 178quantification level, PET ................................... 178receptor-ligand interaction ................................ 181

“translational” imaging method ............................... 152transmission acquisition and emission scans

scanning protocol non-human primate MPTP ..........................................170, 173–174

scanning protocol, rodents ......................... 170–172radionuclide counting statistics .......................... 170

R

Radiochemistrycarbon–11 ........................................................ 156–158constraint, positron-emitting nuclides ..................... 154fluorine–18 ...................................................... 158–161labelling position, isotope ................................ 153, 154labelling precursor.................................................... 156pharmacokinetics ............................................. 153–154positron emitters .............................................. 154, 155radiation protection ......................................... 155–156radionuclides production components ..................... 154radiosynthesis, dilution factor .................................. 155radiotracer properties, factors,

radioligand ability .............................................. 153reaction schemes .............................................. 158–161reaction time factor .................................................. 155

Radio frequency (RF) signals ........................................ 136Radiotracer, PET

benzodiazepine receptor ligand ............................... 182chemical reaction ..................................................... 168co-registration ......................................................... 177electrophilic radiofluorination ................................. 159

AnimAl models of movement disorders: volume i 445

Index

in vivo characterization, receptor-ligand interaction .......................................................... 181

propertiesfactors, radioligand ability .................................. 153labelling position, isotope .......................... 153, 154pharmacokinetics ....................................... 153–154

scanning protocolnon-human primate MPTP model ....170, 173–174rodents ....................................................... 170–172

“translational” imaging method ............................... 152Rating scale. See L-DOPA-induced dyskinesia

or MPTP-lesioned primateRat vs. human homology ................................3–9, 317–324

hand movements .............................................. 101–103learning ............................................................ 102–103skilled reaching ................................................ 101, 104

Reach-to-eat. See Skilled reachingResting-state functional MRI (rs-fMRI) .............. 142–143RF signals. See Radio frequency signalsRNA interference (RNAi)

neuronal cellsdescription ........................................................... 47dopaminergic target gene ..................................... 48neuronal dysfunction ........................................... 48non-neuronal somatic cells ............................ 48–496-OHDA exposure .............................................. 49SID–1 ............................................................ 49–50

protein misfolding ..................................................... 40protein misfolding ..................................................... 40scoring aggregation .............................................. 42–43a-syn misfolding ................................................. 40–41a-syn proteotoxicity ............................................ 42–43

Rotarod testapparatus...............................................71–77, 122, 289distracting stimuli ...................................................... 75footing, loss of ........................................................... 75methods ...................... 73, 122–123, 289–290, 294, 360

low variance data sets ........................................... 73training trials ........ 73, 122–123, 289–290, 294, 360

motor function ........................................................... 71weight differences ...................................................... 75

Rotometeranimal harness ................................................. 303–304cam and pivot assembly ........................................... 304data recording .................................................. 304–305description ............................................................... 301species issues ............................................................ 305test chamber .................................................... 301–303

rs-fMRI. See Resting-state functional MRI

S

SHIRPA screen testmethods

force touch ........................................................... 69negative geotaxis .................................................. 70

positional passivity ............................................... 68rectangular test arena ........................................... 68righting reflex ...................................................... 70toe pinch .............................................................. 70visual placing........................................................ 69

non-parametric analyses ............................................ 71scores, scale ................................................................ 68

Single pellet reachingapparatus dimensions ................................................. 89box ............................................................................. 88frontal view .............................................................. 100gestures ............................................................ 101–102video recording .......................................................... 89

Skilled reachingallied gestures................................................... 101–102compensation assessment................................. 103–104description ................................................................. 87disorders, human ..................................................... 104forelimb movement primitives ................................. 102humans .................................................................... 102independent forelimb............................................... 288methods

apparatus habituation..................................... 88–90establishment, hand dominance ........................... 90feeding and food familiarization .......................... 88gestures .......................................................... 93–95grasping movements .................................. 100–101hand-shaping transitions ............................... 98–99movement elements ....................................... 95–98performance, end-point measures .................. 90–91reaching trial .................................................. 91–93video recording .................................................... 89

motor learning ................................................. 102–103outcome parameters ................................................. 288reaching tasks, types .................................................. 88recovery, function ..................................................... 103single pellet reaching task ........................................ 101

Skill learning ................................................................. 321Social discrimination test....................................... 124–125Somatosensory evoked potentials (SSEPs) ............ 143, 144Spinal cord systems. See Volume II (Neuromethods 62)Spiny projection neurons (SPNs)

classes ...................................................................... 196dendritic anatomy

deconvolution .................................................... 200direct volume rendering ............................. 200–202limitations .......................................................... 202z-stack ....................................................... 197–200

dendritic field diameter ........................................... 197SPN dendritic anatomy

deconvolution .......................................................... 200direct volume rendering ................................... 200–202limitations ........................................................ 202–2032PLSM .................................................................... 197z-stack ............................................................. 197–200

446 AnimAl models of movement disorders: volume i

Index

SSEPs. See Somatosensory evoked potentialsStroke

early phaseADC threshold and reduction ................... 138–139MR angiography ................................................ 140T1-weighted MRI ............................................. 140T2 relaxation time ..................................... 139–140

ledged beam test .............................................. 328–329limb-use asymmetry ........................................ 327–328rodent models

behavioral tests................................................... 326permanent occlusion .......................................... 326

somatosensory asymmetriessensory stimuli ................................................... 330stimulus contact and removal ............................. 330

structural damagechronic phase ............................................. 140–141early phase ................................................. 138–140

tactile stimulation test .............................................. 329T2-weighted imaging, chronic phase............... 140–141vibrissae-elicited limb placing .......................... 330–331

T

TAC. See PET; Time-activity curveTamoxifen

conditional gene targeting vectors ................... 256–258inducible expression vector cloning ......................... 251inducible gene expression cells ................................. 249b-galactosidase reporter cassette ...................... 253–254large-scale mutagenesis programmes ............... 254–256ORF-coded protein ................................................. 250plasmids ................................................................... 249potential duplication ................................................ 254primers ............................................................. 249–250RMCE positive ES cell clones ................................ 253Rosa26 locus .................................................... 250–253somatic cells ..................................................... 253–254targeting vector generation ...................................... 259

Transgenic micebehavioural screens ...............................65–86, 109–134blastocyst injection................................................... 253CreERT2 ........................................................... 247, 259gene expression ........................................................ 246production ............................................................... 250Tm1a mice ............................................................... 255

Transient receptor potential melastatin 7 (TRPM7) gene .............................................. 20–21

Translation deficits ............................................................ 8Parkinson’s disease ..................................................... 23PINK1 ...................................................................... 15zebrafish .................................................................... 25

Translocator protein (TSPO), 184

TRPM7 gene. See Transient receptor potential melastatin 7 gene

TSPO. See Translocator proteinTwo-photon laser scanning microscopy (2PLSM)

imaging .................................................................... 208mitochondrial function ............................................ 210scanning software .................................................... 205software packages .................................................... 204young adult mice ..................................................... 212

U

Unified Parkinson’s disease rating scale (UPDRS) ................................................... 409, 423

V

Validityconstruct ...................................................................... 4face .......................................................................... 5, 6Parkinson’s disease ............................310, 317, 326, 425Huntington’s disease (HD) ................................ 5–6, 74rodents .................................. 5, 6, 8, 105, 310, 317, 326rodent-human extrapolations....................................... 4

Vertical pole test .................................................... 120–122Vertebrate model organism. See ZebrafishVibrissae-elicited limb placing

automatic placing response ...................................... 3306-OHDA lesions ..................................................... 331unilateral nigrostriatal lesions .................................. 331

W

Western blot alpha-synuclein assaysdescription, structural .......................................... 58–59transgenic a–synuclein ........................................ 58–59

Z

ZebrafishCNS systems and motor behaviors

basal ganglia and cerebellum, role ........................ 14brainstem and spinal cord .................................... 16calcium imaging ................................................... 14genetic approaches ............................................... 14locomotor....................................................... 18–20movement ...................................................... 16–18mutants .......................................................... 20–21neurotransmitter ............................................ 15–16Purkinje cells........................................................ 14telencephalon, ray-finned fish ........................ 12–13upper motor neuron and thalamus

functions ........................................................ 12models of Parkinson’s disease

DJ1 expression and LRRK2

AnimAl models of movement disorders: volume i 447

Index

Mutations ...................................................... 20–24MPTP ........................................................... 21–22off-target effects............................................. 23, 25parkin mutants ............................................... 23, 25PINK1 translation and mutant ...................... 23–25

description ........................................................... 11–12PD ....................................................................... 21–25Tol2 transposon system ............................................. 26zinc finger nuclease method .............................. 26, 249

Zinc-finger nucleases (ZFNs) ................................. 26, 249