1. General Neurophysiology Axonal transport Transduction of signals at the cellular level Degeneration and regeneration in the nervous system Neurophysiological principles of behavior Olga Vajnerová, Department of physiology, 2nd Medical School Charles University Prague

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

3. Anterograde axonal transport fast (100 - 400 mm/day) MAP kinesin/mikrotubules moves neurotransmitters in vesicles and mitochondria slow (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),

4. Axonal transport in the pathogenesis of diseases Rabies virus (madness, hydrofobia) Replicates in muscle cell Axon terminal (endocytosis) Retrograde transport to the cell body Neurons produce copies of the virus CNS – behavioral changes Neurons innervating the salivary glands (anterograde transport) Tetanus toxin (produced by Clostridium tetani) Toxin is transported retrogradely in nerve cells Tetanus toxin is released from the nerve cell body Taken up by the terminals of neighboring neurons http://cs.wikipedia.o rg/wiki/Vzteklina

5. Axonal transport as a research tool Tracer studies (investigation of neuronal connections) Anterograde axonal transport Radioactively 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 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 preparation can be visualized. Injection to axon terminals can identify cell body

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

7. Axon – the signal is carried without decrement Threshold All or nothing law

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

9. Signal propagation from dendrite to initial segment

10. Origin of the AP electrical stimulus sensory input neurotransmitter on synapses

11. Sensory input Sensory transduction – conversion of stimulus from the external or internal environment into an electrical signal Signals: sound wave (auditory), taste, light photon (vision), touch, pain, olfaction, muscle spindle, PhototransductionChemotransductionMechanotransduction

12. Sensory input Sensory transduction – conversion of stimulus from the external or internal environment into an electrical signal Signals: taste, light photon (vision), touch, pain, olfaction, muscle spindle, PhototransductionChemotransductionMechanotransduction sound wave (auditory),

13. Sensory input Sensory transduction – conversion of stimulus from the external or internal environment into an electrical signal Signals: light photon (vision), touch, pain, olfaction, muscle spindle, PhototransductionChemotransduction taste, Mechanotransduction sound wave (auditory),

14. Sensory input Sensory transduction – conversion of stimulus from the external or internal environment into an electrical signal Signals: touch, pain, olfaction, muscle spindle, Phototransduction light photon (vision), Chemotransduction taste, Mechanotransduction sound wave (auditory),

15. Sensory input Sensory transduction – conversion of stimulus from the external or internal environment into an electrical signal Signals: pain, olfaction, muscle spindle, Phototransduction light photon (vision), Chemotransduction taste, Mechanotransduction sound wave (auditory), touch,

16. Sensory input Sensory transduction – conversion of stimulus from the external or internal environment into an electrical signal Signals:, olfaction, muscle spindle, Phototransduction light photon (vision), Chemotransduction taste, pain Mechanotransduction sound wave (auditory), touch,

17. Sensory input Sensory transduction – conversion of stimulus from the external or internal environment into an electrical signal Signals: muscle spindle, Phototransduction light photon (vision), Chemotransduction taste, pain olfaction Mechanotransduction sound wave (auditory), touch,

18. Sensory input Sensory transduction – conversion of stimulus from the external or internal environment into an electrical signal Signals:, Phototransduction light photon (vision), Chemotransduction taste, pain olfaction Mechanotransduction sound wave (auditory), touch, muscle spindle

19. Sensory input Sensory transduction – conversion of stimulus from the external or internal environment into an electrical signal Osmoreceptors, thermoreceptors Phototransduction light photon (vision), Chemotransduction taste, pain olfaction Mechanotransduction sound wave (auditory), touch, muscle spindle

20. Origin of the AP electrical stimulus sensory input neurotransmitter on synapses

21. Axonal part of the neuron AP – voltage-gated Ca 2+ channels –neurotransmitter release Arrival of an AP in the terminal opens voltage- gated Ca 2+ channels, causing Ca 2+ influx, which in turn triggers transmitter release.

22. Somatodendritic part of neuron Receptors on the postsynaptic membrane Excitatory receptors open Na +, Ca 2+ channels membrane depolarization Inhibitory receptors open K +, Cl - channels membrane hyperpolarization EPSP – excitatory postsynaptic potential IPSP – inhibitory postsynaptic potential

23. Excitatory and inhibitory postsynaptic potential

24. Interaction of synapses

25. Summation of signals spatial and temporal

26. Potential changes in the area of trigger zone (axon hillock) Interaction of all synapses Spatial summation – currents from multiple inputs add algebraically up Temporal summation –if another APs arrive at intervals shorter than the duration of the EPSP Trigger zone

27. Transduction of signals at the cellular level EPSP IPSP Initial segment AP Ca2+ influx Neurotransmitter Neurotransmitter releasing

28. Neuronal activity in transmission of signals Discharge configurations of various cells EPSP IPSP

29. 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 Ca 2+ channels, localized in the dendrites 3.AHP, after-hyperpolarization, Ca 2+ sensitive K + channels 4.Rebound depolarization, low threshold Ca 2+ channels, (probably localized at the level of the soma RMP Threshold Hammond, C.:Cellular and Molecular Neurobiology. Academic Press, San Diego 2001: str. 407.

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

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

32. Injury of the axon in PNS Compression, 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 Büngner) Proximal axon sprouts (axonal sprouting) Prognosis quo ad functionem Compression, crushing – good, Schwann cells remain in their original orientation, axons can find their original targets Cutting – worse, regeneration is less likely to occure

33. Myelin sheath formation in CNS

34. Injury of the axon in CNS Oligodendrocytes do not create a basal lamina and a band of Büngner Regeneration to a functional state is impossible Trauma of the CNS proliferation and hypertrophy of astrocytes, astrocytic scar

35. Injury of the axon in PNS after amputation Amputation of the limb Proximal stump fail to enter the Schwann cell tube, instead ending blindly in connective tissue Blind ends rolle themselves into a ball and form a neuroma – phantom pain

36. Neurophysiological principles of behavior Ivan Petrovich Pavlov Russia nobelist 1904 Research on reflexes 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. Fixed action pattern innate endogenous fireing activity produced by a specific neural network Simple external sensory stimulus release complex activity An instinctive behavioral sequence that is indivisible and runs to completion stimulus known as a sign stimulus (releaser) – consumatory behavior

45. Greylag goose will roll a displaced egg near its nest back to the others with its beak. The sight of the displaced egg triggers this mechanism. If the egg is taken away, the animal continues with the behavior, pulling its head back as if an imaginary egg is still being maneuvered by the underside of its beak The egg rolling behavior of a Greylag Goose

46. Neurophysiological principles of behavior - summary Innate forms of behavior Unconditioned reflex An instinctive behavioral sequence Central pattern generator Acquired forms of behavior Learning and memory (conditioned reflex)

47. Neurophysiological principles of behavior - summary Innate forms of behavior Unconditioned reflex An instinctive behavioral sequence Central pattern generator Acquired forms of behavior Learning and memory (conditioned reflex) Taste stimulus – salivation, mimic expresion for anger, bike riding, breathing movements, vizual stimulus - salivation

48. Neurophysiological principles of behavior - summary Innate forms of behavior Unconditioned reflex Taste stimulus – salivation An instinctive behavioral sequence mimic expresion for anger Central pattern generator breathing movements Acquired forms of behavior Learning and memory bike riding (conditioned reflex vizual stimulus - salivation),,,,

49. conditioned reflex : salivation - visual stimulus Thanks for attention