General Neurophysiology

1. General Neurophysiology Axonal transport Transductionofsignalsatthecellularlevel Classificationof nerve fibres Reflexesandpatterngeneration Olga Vajnerová, Department of physiology, 2nd Medical School Charles University Prague

2. Axonal transport (axoplasmatic transport) Anterograde Proteosynthesis in the cell body only (ER, Golgi apparatus) Retrograde Moving the chemical signals from periphery

3. Anterogradeaxonal transportfast (100 - 400 mm/day)MAP kinesin/mikrotubulesmoves neurotransmittersin vesicles and mitochondriaslow (0,5 – 10 mm/day)unknown mechanism structural components (cytoskeleton - aktin, myosin, tubulin), metabolic componentsRetrograde axonal transportfast (50 - 250 mm/day) MAP dynein/ mikrotubulesold mitochondria, vesicles (pinocytosis, receptor-mediated endocytosis in axon terminals, transport of e.g. growths factors),

4. Axonal transport in thepathogenesisofdiseases Rabies virus (madness, hydrofobia) Replicates in muscle cell Axon terminal (endocytosis) Retrograde transport to the cell body Neuronsproducecopiesofthe virus CNS – behavioralchanges Neuronsinnervatingthesalivaryglands (anterograde transport) Tetanus toxin (produced by Clostridium tetani) Toxin istransportedretrogradely in nerve cells Tetanus toxin isreleasedfromthe nerve cell body Takenup by theterminalsofneighboringneurons http://cs.wikipedia.org/wiki/Vzteklina

5. Axonal transport as a research tool Tracer studies (investigation of neuronal connections) Anterogradeaxonal transport Radioactively labeled amino acids (incorporated into proteins, transported in an anterograde direction, detectedby autoradiography) Injection into a group of neuronal cell bodies can identify axonal distribution Retrograde axonal transport Horseradish peroxidase is injected into regions containing axon terminals. Is taken up and transported retrogradely to the cell body. After histology preparationcan be visualized. Injection to axon terminalscan identify cell body

6. Transduction of signals at the cellular level Somatodendritic part – passive conduction of the signal, with decrement Axonal part –action potential, spreading without decrement, all-or-nothing law

7. Resting membrane potential Every living cell in the organism

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

9. K+ - - - + Ai + + + + When the membrane would be permeable for K+ only • K+ 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 K+ Na+ Cl-

10. Action potential Axonal part –actionpotential Threshold stimulus

11. Axon – the signal is carried without decrement Allornothinglaw

12. Originofthe APelectrical stimulusordepolarisationofinitial segment

13. Dendrite and cell body – signal is propagated with decrement

14. Signalpropagationfrom dendrite to initial segment

15. ExcitationorinhibitionofdendritesandsomaSYNAPSES

16. Axonal part of the neuronAP – voltage-gated Ca2+ channels –neurotransmitter release Arrivalofan AP in theterminalopensvoltage-gated Ca2+channels, causing Ca2+influx, which in turntriggerstransmitterrelease.

17. Somatodendritic part of neuron Receptors on the postsynaptic membrane • Excitatory receptors open Na+, Ca2+channelsmembrane depolarization • Inhibitoryreceptors open K+, Cl-channels membrane hyperpolarization • EPSP – excitatory postsynaptic potential • IPSP – inhibitory postsynaptic potential

18. Excitatory and inhibitory postsynaptic potential

19. Interaction of synapses

20. Summation of signals spatial and temporal

21. Potential changes in the area of trigger zone (axon hillock) • Interaction of all synapses • Spatial summation – currentsfrom multiple inputs add algebraically up • Temporal summation –if another APsarrive at intervals shorter than the duration of the EPSP Trigger zone

22. Transductionofsignalsatthecellularlevel 2. EPSP IPSP 3. Initial segmentdepolarisation 4. AP 5. Ca2+ influx 1. Neurotransmitterreleasing 1. Synapse Neurotransmitter

23. Neuronalactivity in transmissionofsignalsDischargeconfigurationsofvariouscells EPSP IPSP

24. Influence of one cell on the signal transmission 1.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 dendrites 3.AHP, after-hyperpolarization, Ca2+ sensitive K+ channels 4.Rebound depolarization, low threshold Ca2+ channels, (probably localized at the level of the soma Threshold RMP Hammond, C.:Cellular and Molecular Neurobiology. Academic Press, San Diego 2001: str. 407.

25. Classificationof nerve fibres

27. The compound action potential Program neurolab Biphasicrecordingfromwhole nerve Differencesbetweenthevelocitiesofindividualfibresgiverise to a dispersedcompoundactionpotential

28. Compound action potential – all types of nerve fibres

29. Classification of nerve fibres

31. Classification of nerve fibres

32. Two different systems are in use for classifying nerve fibres

35. General Neurophysiology Axonal transport Transductionofsignalsatthecellularlevel Classificationof nerve fibres Reflexesandpatterngeneration

36. Research on reflexes Ivan Petrovich Pavlov Russia nobelist 1904 Sir Charles Scott Sherrington Great Britain nobelist 1932

37. Reflex arch Knee-jerk reflex

38. Behavior as a chain of reflexes? LOCUST Two pairs of wings Each pair beat in synchrony but the rear wings lead the front wings in the beat cycle by about 10% Proper delay between contractions of the front and rear wing muscles

39. Donald Wilson’s Experiment in 1961

40. To confirm the hypothesis Identify the reflexes that are responsible for the flight pattern Deafferentaion = the elimination of sensory input into the CNS Remove sense organs at the bases of the wings Cut of the wings Removed other parts of locust s body that contained sense organs Unexpected result Motor signals to the flight muscles still came at the proper time to keep the wings beat correctly synchronized

41. Extreme experiment Reduced the animal to a head and the floor of the thorax and the thoracic nerve cord Elecrodes on the stumps of the nerves that had innervated the removed flight muscles Motor pattern recorded in the absence of any movement of part of animal – fictive pattern Locust flight systém did not require sensory feedback to provide timing cues for rhythm generation Network of neurons Oscillator, pacemaker, central pattern generator

42. Central pattern generator Model of the CPG for control of muscles during swimming in lamprey

43. Central pattern generators A network of neurons capable of producing a properly timed pattern of motor impulses in the absence of any sensory feedback. Swimming Wing beating Walking Gallop, trot Licking Scratching Breathing Chewing

44. Summary Classificationof nerve fibres

45. Summary Transductionofsignalsatthecellularlevel 2. EPSP IPSP 3. Initial segmentdepolarisation 4. AP 5. Ca2+ influx Neurotransmitter releasing 1. Synapse Neurotransmitter

46. Questions?