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

2. 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)

3. 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 15-20 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. 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.

6. University of Jordan 6 Comparison between Presynaptic and Postsynaptic inhibition  IPSP need 1-2 msec to be formed and lasts only 15-20 msec in contrast to presynaptic inhibition that need 15-20 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

7. 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.

8. 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

9. University of Jordan 9 Graded Potentials

10. 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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12. University of Jordan 12 Summation of Postsynaptic Potentials

13. 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.

14. 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 0.5 - 1.0 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

15. 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.

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

17. University of Jordan 17 Stimulus strength and graded potentials

18. University of Jordan 18 Summation

19. 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

20. University of Jordan 20 Action Potentials

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22. 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.

23. 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

24. 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

25. 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.

26. 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

27. 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 (0.3-0.5 msec)  Synaptic delay is the rate-limiting step of neural transmission

28. 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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