Transcript General Neurophysiology - Univerzita Karlova v Praze

General Neurophysiology
Axonal transport
Degeneration and regeneration in the nervous
system
Transduction of signals at the cellular level
Reflex arch
Central pattern generator
Axonal transport
(axoplasmatic transport)
Anterograde
Proteosynthesis in the cell body
only (ER, Golgi apparatus)
Retrograde
Moving the chemical signals from
periphery
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
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
Axonal transport as a research tool
Tracer studies
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
Degeneration and regeneration
in the nervous system
• Neurons do not proliferate
•
•
•
•
Exceptions
- olfactory epithelium
- dentatum gyrus (stem cells)
- olfactory bulb
• Generaly
• Lost neurons are not replaced (proliferation of glia,
astrocytic scar)
Myelin sheath of axons in PNS
(a membranous wrapping around the axon)
Myelin sheath of axons in PNS
(a basal lamina)
Basal lamina
Myelin sheath formation in CNS
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 – goodSchwann 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 PNS
• 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
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
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
Dendrite and cell body – signal is propagated with decrement
Signal propagation from dendrite to initial segment
Origin of the AP
electrical stimulus
neurotransmitter on synapses
Axonal part of the neuron
AP – voltage-gated Ca2+ channels –neurotransmitter release
Arrival of an AP in the
terminal opens voltagegated 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+ channels
membrane 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 signals
spatial and temporal
Transduction of signals at the
cellular level
EPSP
IPSP
Initial
segment
AP
Ca2+ influx
Neurotransmitter
Neurotransmitter
releasing
EPSP
IPSP
Neuronal
activity in
transmission
of signals
Discharge
configurations
of various cells
Influence of one cell
on the signal
transmission
1.AP, activation of the voltagedependent Na+ channels (soma,
area of the initial segment)
2. ADP, after-depolarization,
acctivation of a high threshold
Ca2+ channels, localized in the
dendrites
Threshold
RMP
3.AHP, after-hyperpolarization,
Ca2+ sensitive K+ channels
4.Rebound depolarization, low
threshold Ca2+ channels, deinactivated during the AHP,
activated when the depolarization
decreases (probably localized at
the level of the soma
Reflex arch
Knee-jerk
reflex
Research on reflexes
Ivan Petrovich Pavlov
Russia
nobelist 1904
Sir Charles Scott Sherrington
Great Britain
nobelist 1932
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
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 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
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
Central pattern
generator
Model 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.
Swimming
Wing beating
Walking
Gallop, trot
Licking
Scratching
Breathing
Summary
Axonal transport
(axoplasmatic transport)
Anterograde
Proteosynthesis in the cell body
only (ER, Golgi apparatus)
Retrograde
Moving the chemical signals from
periphery
Degeneration and regeneration
in the nervous system
• Damaged (differenciated) neurons are not replaced
Trauma of the CNS – glial scarf
• Axons in CNS
• Axons in PNS
Transduction of signals at the
cellular level
EPSP
IPSP
Initial
segment
AP
Ca2+ influx
Neurotransmitter
Neurotransmitter
releasing
Reflex arch
Central pattern
generators
Pacemakers