General NeurophysiologyAxonal transportTransduction of signals at the cellular levelClassification of nerve fibres

Olga Vajnerov, Department of physiology, 2nd Medical School Charles University Prague

(axoplasmatic transport)

AnterogradeProteosynthesis in the cell body only (ER, Golgi apparatus)

RetrogradeMoving the chemical signals from peripheryAxonal transport

Anterograde axonal transport fast (100 - 400 mm/day)MAP kinesin/mikrotubules moves neurotransmitters in vesicles and mitochondriaslow (0,5 10 mm/day)unknown mechanism structural components (cytoskeleton - aktin, myosin, tubulin), metabolic components Retrograde axonal transport fast (50 - 250 mm/day) MAP dynein/ mikrotubules old mitochondria, vesicles (pinocytosis, receptor-mediated endocytosis in axon terminals, transport of e.g. growths factors),

Axonal transport in the pathogenesis of diseasesRabies virus (madness, hydrofobia)Replicates in muscle cellAxon terminal (endocytosis)Retrograde transport to the cell bodyNeurons produce copies of the virusCNS behavioral changesNeurons innervating the salivary glands (anterograde transport)

Tetanus toxin (produced by Clostridium tetani) Toxin is transported retrogradely in nerve cellsTetanus toxin is released from the nerve cell bodyTaken up by the terminals of neighboring neuronshttp://cs.wikipedia.org/wiki/Vzteklina

Axonal transport as a research tool

Tracer studies (investigation of neuronal connections)

Anterograde axonal transportRadioactively labeled amino acids (incorporated into proteins, transported in an anterograde direction, detected by autoradiography)Injection into a group of neuronal cell bodies can identify axonal distributionRetrograde axonal transportHorseradish peroxidase is injected into regions containing axon terminals. Is taken up and transported retrogradely to the cell body. After histology preparation can be visualized.Injection to axon terminals can identify cell body

Transduction of signals at the cellular levelAxonal part action potential, spreading without decrement, all-or-nothing law

Somatodendritic part passive conductionof the signal, with decrement

Resting membrane potentialEvery living cellin the organism

Membrane potential is not a potential. It is a difference of two potentials so it is a voltage, in fact.

When the membrane would be permeable for K+ onlyK+ escapes out of the cell along concetration gradient

A- cannot leave the cell

Greater number of positive charges is on the outer side of the membrane

Na+Cl-K+

Transduction of signals at the cellular levelAxonal part action potential, spreading without decrement, all-or-nothing law

Axon the signal is carried without decrementThreshold

All or nothing law

Membrane conductance for Na+ a pro K+Action potential

Action potential

Propagation of the action potential along the axon

Transduction of signals at the cellular levelSomatodendritic part passive conductionof the signal, with decrement

Dendrite and cell body signal is propagated with decrement

Signal propagation from dendrite to initial segment

Origin of the electrical signal

electrical stimulus

sensory input neurotransmitter on synapses

Axonal part of the neuron

AP voltage-gated Ca2+ channels neurotransmitter releaseArrival of an AP in the terminal opens voltage-gated Ca2+ channels, causing Ca2+ influx, which in turn triggers transmitter release.

Somatodendritic part of neuronReceptors on the postsynaptic membraneExcitatory receptors open Na+, Ca2+ channelsmembrane depolarizationInhibitory receptors open K+, Cl- channels membrane hyperpolarization

EPSP excitatory postsynaptic potentialIPSP inhibitory postsynaptic potential

Excitatory and inhibitory postsynaptic potential

Interaction of synapses

Summation of signalsspatial and temporal

Potential changes in the area of trigger zone (axon hillock)Interaction of all synapsesSpatial summation currents from multiple inputs add algebraically upTemporal summation if another APs arrive at intervals shorter than the duration of the EPSP

Trigger zone

Transduction of signals at the cellular levelEPSPIPSPInitial segmentAPCa2+ influxNeurotransmitterNeurotransmitter releasing

Neuronal activity in transmission of signals

Discharge configurationsof various cellsEPSPIPSP

Influence of one cell on the signal transmission1.AP, activation of the voltage-dependent Na+ channels (soma, area of the initial segment)2. ADP, after-depolarization, acctivation of a high threshold Ca2+ channels, localized in the dendrites3.AHP, after-hyperpolarization, Ca2+ sensitive K+ channels4.Rebound depolarization, low threshold Ca2+ channels, (probably localized at the level of the soma RMPThresholdHammond, C.:Cellular and Molecular Neurobiology. Academic Press, San Diego 2001: str. 407.

Origin of the electrical signal

electrical stimulus

sensory inputneurotransmitter on synapses

Sensory inputSensory transduction conversion of stimulus from the external or internal environment into an electrical signalSignals: sound wave (auditory), taste, light photon (vision), touch, pain, olfaction, muscle spindle, PhototransductionChemotransductionMechanotransduction

Sensory inputSensory transduction conversion of stimulus from the external or internal environment into an electrical signalOsmoreceptors, thermoreceptorsPhototransduction light photon (vision), Chemotransduction taste, pain olfactionMechanotransduction sound wave (auditory), touch, muscle spindle

Classification of nerve fibres

The compound action potentialDiferences between the velocities of individual fibres give rise to a dispersed compoud action potential

Program neurolab

Compound action potential all types of nerve fibres

Classification of nerve fibres

Classification of nerve fibres

Two different systems are in use for classifying nerve fibres

Myelin sheath of axons in PNS(a membranous wrapping around the axon)Degeneration and regeneration in the nervous system

Myelin sheath of axons in PNS(a basal lamina)Basal lamina

Injury of the axon in PNSCompression, crushing, cutting degeneration of the distal axon - but the cell body remains intact (Wallerian degeneration, axon is removed by macrophages)Schwann cells remain and their basal lamina (band of Bngner) Proximal axon sprouts (axonal sprouting)Prognosis quo ad functionemCompression, crushing good, Schwann cells remain in their original orientation, axons can find their original targetsCutting worse, regeneration is less likely to occure

Myelin sheath formation in CNS

Injury of the axon in CNS

Oligodendrocytes do not create a basal lamina and a band of BngnerRegeneration to a functional state is impossible

Trauma of the CNS

proliferation and hypertrophy of astrocytes, astrocytic scar

Injury of the axon in PNS after amputationAmputation of the limbProximal stump fail to enter the Schwann cell tube, instead ending blindly in connective tissueBlind ends rolle themselves into a ball and form a neuroma phantom pain

*Rabies, madness, hydrophobia: viral neuroivasive desease, encephalitis, incubation period several month,symptoms malaise, excitement, depression, pain, paresis, unable to swallow water, mania lethargy, coma, respiratory insufficiency