General Neurophysiology Axonal transport Transduction of signals at the cellular level Degeneration...

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

(axoplasmatic transport)

Anterograde

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

RetrogradeMoving the chemical signals from periphery

Axonal transport

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),

Axonal transport in the pathogenesis of diseases

Rabies 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 cells

Tetanus toxin is released from the nerve cell body

Taken up by the terminals of neighboring neurons

http://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 level

Axonal part –action potential, spreading without decrement, all-or-nothing law

Somatodendritic part –

passive conduction

of the signal, with decrement

Axon – the signal is carried without decrement

Threshold

All or nothing law

Dendrite and cell body – signal is propagated with decrement

Signal propagation from dendrite to initial segment

Origin of the AP

electrical stimulus

sensory input

neurotransmitter on synapses

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,

Phototransduction Chemotransduction Mechanotransduction

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,

Phototransduction Chemotransduction Mechanotransduction sound wave (auditory),

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,

Phototransduction Chemotransduction taste,

Mechanotransduction sound wave (auditory),

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),

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,

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,

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,

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

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

Origin of the AP

electrical stimulus

sensory input

neurotransmitter on synapses

Axonal part of the neuron

AP – 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

Receptors on the postsynaptic membrane

• Excitatory receptors open Na+, Ca2+ channelsmembrane depolarization

• Inhibitory receptors open K+, Cl- channels

membrane hyperpolarization

• EPSP – excitatory postsynaptic potential

• IPSP – 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 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

Transduction of signals at the cellular level

EPSPIPSP

Initial segment AP Ca2+ influx

Neurotransmitter

Neurotransmitter releasing

Neuronal activity in

transmission of signals

Discharge configurationsof various cells

EPSPIPSP

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

RMP

Threshold

Hammond, C.:Cellular and Molecular Neurobiology.

Academic Press, San Diego 2001: str. 407.

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 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

Myelin sheath formation 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

• 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

Neurophysiological principles of behavior

Ivan Petrovich PavlovRussia nobelist 1904

Research on reflexes

Sir Charles Scott SherringtonGreat Britain nobelist 1932

Reflex arch

Knee-jerk reflex

Behavior as a chain of reflexes?

LOCUSTTwo 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

Donald Wilson’s Experiment in 1961

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 wingsCut of the wingsRemoved other parts of locust s body that contained sense organsUnexpected resultMotor signals to the flight muscles still came at the proper time to keep the wings beat correctly synchronized

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 patternLocust flight systém did not require sensory feedback to provide timing cues for rhythm generation

Network of neuronsOscillator, pacemaker, central pattern generator

Central pattern generatorModel of the CPG for control of muscles during swimming in lamprey

Central pattern generators

A network of neurons capable of producing a properly timed pattern of motor impulses in the absence of any sensory feedback.

SwimmingWing beatingWalkingGallop, trotLickingScratchingBreathingChewing

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

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

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)

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

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)

,,,,

conditioned reflex : salivation - visual stimulus

Thanks for attention