General Neurophysiology Axonal transport Transduction of signals at the cellular level Classification of nerve fibres Reflexes and pattern generation Olga Vajnerová, Department of physiology, 2nd Medical School Charles University Prague

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

Anterograde axonal transport fast ( 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 ( 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 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 rg/wiki/Vzteklina

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

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

Resting membrane potential Every living cell in the organism

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

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+K+ Ai Na+ Cl- K+

Action potential Axonal part –action potential Threshold stimulus

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

Origin of the AP electrical stimulus or depolarisation of initial segment

Dendrite and cell body – signal is propagated with decrement

Signal propagation from dendrite to initial segment

Excitation or inhibition of dendrites and soma SYNAPSES

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.

Somatodendritic part of neuron Receptors on the postsynaptic membrane Excitatory receptors open Na +, Ca 2+ 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 signals spatial 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 4. AP 5. Ca2+ influx 1. Synapse Neurotransmitter 1. Neurotransmitter releasing 2. EPSP IPSP 3. Initial segment depolarisation

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

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.

Classification of nerve fibres

The compound action potential Biphasic recording from whole nerve Differences between the velocities of individual fibres give rise to a dispersed compound action potential Program neurolab

Compound action potential – all types of nerve fibres

Classification of nerve fibres

Two different systems are in use for classifying nerve fibres

General Neurophysiology Axonal transport Transduction of signals at the cellular level Classification of nerve fibres Reflexes and pattern generation

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

Reflex arch Knee-jerk reflex

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 Chewing

Summary Classification of nerve fibres

Summary 4. AP 5. Ca2+ influx 1. Synapse Neurotransmitter Neurotransmitter releasing 2. EPSP IPSP 3. Initial segment depolarisation Transduction of signals at the cellular level

Questions?