University of Jordan1 Physiology of Synapses in the CNS- L4 Faisal I. Mohammed, MD, PhD

University of Jordan 2 Objectives Students should be able to:  Define synapse and list the types of synapse  Describe the mechanism of neurotransmitter release  List the major types of neurotransmitters (NT)  Compare the small molecules NT and Neuropeptides  Describe the resting membrane potential and Nernst Equation  Determine the how EPSP, IPSP and Presynaptic inhibition develops  Describe summation of EPSP and IPSP  Describe the characteristics of synapse (Fatigue and Delay)

Characteristics of Postsynaptic Potentials (EPSP and IPSP) It is a local potential, propagates for a short distance It is graded potential so it can be summated It takes 1-2 msec to develop and stays for msec Its amplitude is directly proportional to the strength of the stimulus (amount of NT) It is decremental potential (decreases as it travels) It is due to a change in the permeability of ligand- gated (chemically) channels

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5 Presynaptic Inhibition  Activation of presynaptic synapses decreases ability of Ca + channels to open on the presynaptic terminals.  inhibition of Ca + influx results in reduced neuronal excitation  Presynaptic inhibition occurs in many of the sensory pathways in the nervous system.  The neurotransmitter is usually GABA.

University of Jordan 6 Comparison between Presynaptic and Postsynaptic inhibition  IPSP need 1-2 msec to be formed and lasts only msec in contrast to presynaptic inhibition that need msec to develop and last longer than 100 msec sometimes  IPSP leads to changes in the postsynaptic membrane potential in contrast to presynaptic membrane potential where it leads to decrease NT release  Besides all these the site where both work is different

University of Jordan 7 Graded Potentials  Small deviations from resting potential of -70mV  hyperpolarization = membrane has become more negative  depolarization = membrane has become more positive  The signals are graded, meaning they vary in amplitude (size), depending on the strength of the stimulus and localized.  Graded potentials occur most often in the dendrites and cell body of a neuron.

University of Jordan 8  Short-lived, local changes in membrane potential  Decrease in intensity with distance  Their magnitude varies directly with the strength of the stimulus  Sufficiently strong graded potentials can initiate action potentials Graded Potentials

University of Jordan 9 Graded Potentials

University of Jordan 10 Graded Potentials  Voltage changes in graded potentials are decremental  Current is quickly dissipated due to the leaky plasma membrane  Can only travel over short distances

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University of Jordan 12 Summation of Postsynaptic Potentials

University of Jordan 13 Summation  If several presynaptic end bulbs release their neurotransmitter at about the same time, the combined effect may generate a nerve impulse due to summation  Summation may be spatial or temporal.

University of Jordan 14 Summation of Postsynaptic Potentials  Spatial Summation  Excitation of a single presynaptic neuron on a dendrite will almost never induce an action potential in the neuron.  Each terminal on the dendrite accounts for about a mV EPSP.  When multiple terminals are excited simultaneously the EPSP generated may exceed the threshold for firing and induce an action potential.  The rate of firing is directly proportional to the amplitude of the EPSP

University of Jordan 15 Summation of Postsynaptic Potentials  Temporal Summation  A neurotransmitter opens a membrane channel for about 1 msec but a postsynaptic potential lasts for about 15 msec.  A second opening of the same membrane channel can increase the postsynaptic potential to a greater level.  Therefore, the more rapid the rate of terminal stimulation the greater the postsynaptic potential.  Rapidly repeating firings of a small number of terminals can summate to reach the threshold for firing.

University of Jordan 16 Graded potentials in response to opening mechanically-gated channels or ligand- gated channels

University of Jordan 17 Stimulus strength and graded potentials

University of Jordan 18 Summation

University of Jordan 19 Generation of Action Potentials  An action potential (AP) or impulse is a sequence of rapidly occurring events that decrease and eventually reverse the membrane potential (depolarization) and then restore it to the resting state (repolarization).  During an action potential, voltage-gated Na + and K + channels open in sequence (Na + then K + )  According to the all-or-none principle, if a stimulus reaches threshold, the action potential is always the same.  A stronger stimulus will not cause a larger impulse.  An action potential is generated mostly at the axon hillock since it has the lowest threshold compared to the soma or dendrites.  The axon hillock has the highest density of voltage gated Na + channels

University of Jordan 20 Action Potentials

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University of Jordan 22 Facilitation of Neurons  Often the summated postsynaptic potential is excitatory in nature but has not reached threshold levels.  This neuron is said to be facilitated because the potential is nearer the threshold for firing than normal but not yet to the firing level.  It is easy to stimulate this neuron with subsequent input.

University of Jordan 23 Function of Dendrites in Stimulating Neurons  Dendrites spaced in all directions from neuronal soma.  allows signal reception from a large spatial area providing the opportunity for summation of signals from many presynaptic neurons  Dendrites do not transmit action potentials.  they have few voltage gated Na + channels

University of Jordan 24 Dendrite Function Cont.  Dendrites transmit signals by electrotonic conduction.  transmission of current by conduction in the fluids of the dendrites  no generation of action potentials in the dendrites

University of Jordan 25 Special Characteristics of Synaptic Transmission  Fatigue  exhaustion of the stores of transmitter in synaptic terminals.  excitatory synapses are repetitively stimulated at a rapid rate until rate of postsynaptic discharge becomes progressively less.  causes areas of nervous system to lose excitability after a while.  development of fatigue is a protective mechanism against excess neuronal activity.

University of Jordan 26 Special Characteristics of Synaptic Transmission cont.  Post-tetanic facilitation  enhanced responsiveness following repetitive stimulation  mechanism thought to be build-up of calcium ions in the presynaptic terminals  build-up of calcium causes more vesicular release of transmitter  Synaptic delay  the process of neurotransmission takes time, from the delay can calculate the number of neurons in a circuit

University of Jordan 27 Synaptic Delay  Neurotransmitter must be released, diffuse across the synapse cleft, bind to receptor, leads to membrane potential changes that reaches the threshold then the postsynaptic membrane discharges.  Synaptic delay – time needed to do this ( msec)  Synaptic delay is the rate-limiting step of neural transmission

University of Jordan 28 Environmental Changes and Synaptic Transmission  Effect of acidosis  depresses neuronal activity  pH change from 7.4 to 7.0 usually will induce coma  Effect of alkalosis  increases neuronal excitability  pH change from 7.4 to 8.0 usually will induce seizures  Effect of hypoxia  brain highly dependent on oxygen  interruption of brain blood flow for 3 to 7 sec can lead to unconsciousness

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