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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. Axonal transport.

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general neurophysiology

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

slide2

Axonal transport

(axoplasmatic transport)

Anterograde

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

Retrograde

Moving the chemical signals from periphery

slide3

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),

slide4

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.org/wiki/Vzteklina

slide5

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

transduction of signals at the cellular level
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

origin of the ap electrical stimulus sensory input neurotransmitter on synapses
Origin of the APelectrical stimulussensory inputneurotransmitter on synapses
slide11

Sensory input

Sensory transduction – conversion of stimulus from the external or internal environment into an electrical signal

Phototransduction

Chemotransduction

Mechanotransduction

Signals: sound wave (auditory), taste, light photon (vision), touch, pain, olfaction, muscle spindle,

slide12

Sensory input

Sensory transduction – conversion of stimulus from the external or internal environment into an electrical signal

Phototransduction

Chemotransduction

Mechanotransduction sound wave (auditory),

Signals: taste, light photon (vision), touch, pain, olfaction, muscle spindle,

slide13

Sensory input

Sensory transduction – conversion of stimulus from the external or internal environment into an electrical signal

Phototransduction

Chemotransduction taste,

Mechanotransduction sound wave (auditory),

Signals: light photon (vision), touch, pain, olfaction, muscle spindle,

slide14

Sensory input

Sensory transduction – conversion of stimulus from the external or internal environment into an electrical signal

Phototransduction light photon (vision),

Chemotransduction taste,

Mechanotransduction sound wave (auditory),

Signals: touch, pain, olfaction, muscle spindle,

slide15

Sensory input

Sensory transduction – conversion of stimulus from the external or internal environment into an electrical signal

Phototransduction light photon (vision),

Chemotransduction taste,

Mechanotransduction sound wave (auditory),touch,

Signals: pain, olfaction, muscle spindle,

slide16

Sensory input

Sensory transduction – conversion of stimulus from the external or internal environment into an electrical signal

Phototransduction light photon (vision),

Chemotransduction taste,pain

Mechanotransduction sound wave (auditory),touch,

Signals:, olfaction, muscle spindle,

slide17

Sensory input

Sensory transduction – conversion of stimulus from the external or internal environment into an electrical signal

Phototransduction light photon (vision),

Chemotransduction taste,pain olfaction

Mechanotransduction sound wave (auditory),touch,

Signals: muscle spindle,

slide18

Sensory input

Sensory transduction – conversion of stimulus from the external or internal environment into an electrical signal

Phototransduction light photon (vision),

Chemotransduction taste,pain olfaction

Mechanotransduction sound wave (auditory),touch,muscle spindle

Signals:,

slide19

Sensory input

Sensory transduction – conversion of stimulus from the external or internal environment into an electrical signal

Phototransduction light photon (vision),

Chemotransduction taste,pain olfaction

Mechanotransduction sound wave (auditory),touch,muscle spindle

Osmoreceptors, thermoreceptors

axonal part of the neuron ap voltage gated ca 2 channels neurotransmitter release
Axonal part of the neuronAP – voltage-gated Ca2+ channels –neurotransmitter release

Arrival of an AP in the terminal opens voltage-gated Ca2+ channels,

causing Ca2+ influx,

which in turn triggers transmitter release.

somatodendritic part of neuron
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
slide25

Summation of signals

spatial and temporal

potential changes in the area of trigger zone axon hillock
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

transduction of signals at the cellular level27
Transduction of signals at the cellular level

EPSP

IPSP

Initial segment

AP

Ca2+ influx

Neurotransmitter

Neurotransmitter releasing

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

Influence of one cell on the signal transmission

Threshold

RMP

Hammond, C.:Cellular and Molecular Neurobiology. Academic Press, San Diego 2001: str. 407.

injury of the axon in pns
Injury of the axon in PNS
  • Compression, crushing, cutting – degeneration of the distal axon - but the cell body remains intact (Wallerian degeneration, axon is removedby macrophages)
  • Schwann cells remainand 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
injury of the axon in cns
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
injury of the axon in pns after amputation
Injury of the axon in PNS after amputation
  • Amputation of the limb
  • Proximal stumpfail to enter the Schwann cell tube, instead ending blindly in connective tissue
  • Blind ends rolle themselves into a ball and form aneuroma – phantom pain
neurophysiological principles of behavior
Neurophysiological principles of behavior

Research on reflexes

Ivan Petrovich Pavlov

Russia

nobelist 1904

Sir Charles Scott Sherrington

Great Britain

nobelist 1932

reflex arch
Reflex arch

Knee-jerk reflex

behavior as a chain of reflexes
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

to c onfirm the hypothesis
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

extreme experiment
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

slide42

Central pattern generator

Model of the CPG for control of muscles during swimming in lamprey

central pattern generators
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

fixed action pattern innate endogenous fireing activity produced by a specific neural network
Fixed action patterninnate 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

slide45

The egg rolling behavior of a Greylag Goose

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

slide46

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)

slide47

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

slide48

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)

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