Synaptic Transmission BMS131 Fall 2024 PDF

# Synaptic Transmission ## Intended Learning Outcomes - Recall the mode of synaptic transmission - Distinguish between different types of postsynaptic potentials - Differentiate between postsynaptic and presynaptic inhibition - Describe the properties of synaptic transmission - Formulate the type...

# Synaptic Transmission ## Intended Learning Outcomes - Recall the mode of synaptic transmission - Distinguish between different types of postsynaptic potentials - Differentiate between postsynaptic and presynaptic inhibition - Describe the properties of synaptic transmission - Formulate the types and action of neurotransmitters ## What are Synapses? - Information is transmitted in the central nervous system in the form of nerve action potentials, called nerve impulses, through a succession of neurons, one after another **Definition:** Synapse is the junction point from one neuron to the next at which the impulses are transmitted from one neuron to another. ## Synapses Function: - Transmission of action potential (impulse) - through a succession of neurons, one after another. - Modulation of impulses: - Each impulse - may be blocked in its transmission from one neuron to the next - may be changed from a single impulse into repetitive impulses - may be integrated with impulses from other neurons to cause highly complex patterns of impulses in successive neurons. - It is the site of action of many drugs. ### Neural Circuits: - **Convergence:** - In convergence, many presynaptic knobs terminate (converge) on a single postsynaptic neuron. - The signals of many presynaptic neurons are converged on single postsynaptic neuron. - **Divergence:** - In divergence, Single presynaptic neuron terminates on many postsynaptic neurons. - The signal from single presynaptic neuron is diverged to many postsynaptic neurons. - **Convergence and Divergence:** - The brain simultaneously uses both convergence and divergence. ## Synapses Types - **Chemical** - **Electrical** - **Conjoint** ### 1. Chemical Synapses - They are the most common type of synapses in human being CNS. - At chemical synapse, the axon of one neuron (presynaptic neuron) terminates on the dendrites, soma, or axon of another neuron (postsynaptic neuron). - Thus, synapses may be: - axo-axonic (most excitable, due to presence of high number of Na+ channel, low threshold of stimulation) - axo-dendritic (least excitable); or - axo-somatic. - There is no protoplasmic continuity between presynaptic and postsynaptic neurons, but a space called synaptic cleft with 20-40 nm width. - The ends of the presynaptic fibers are generally enlarged to form terminal boutons or synaptic knobs. - On average, each neuron divides to form over 2000 synaptic knobs. - knobs from many presynaptic neurons terminate on postsynaptic neurons. Thus, communication between neurons is very complex. - Synapses are dynamic structures, increasing and decreasing in complexity and number with use and experience. - Presynaptic terminal contains: - Many mitochondria, and - Many membrane-enclosed vesicles, which contain neurotransmitters. - The vesicles within presynaptic terminals are synthesized in the neuronal cell body and transported along the axon to the endings. - Excitation of presynaptic neurons results in release of the neurotransmitter by exocytosis in the synaptic cleft which then binds to a specific receptor on the postsynaptic neuron to excite the neuron, inhibit it, or modify its sensitivity in some other way. - The excitation or inhibition depends on: - The neurotransmitter - The type of the receptor on postsynaptic neuron - The enzymatic machine of postsynaptic neuron. - More than 50 important neurotransmitters have been discovered thus far. Some of the best known are acetylcholine, norepinephrine, epinephrine, histamine, gamma-aminobutyric acid (GABA), glycine, serotonin, and glutamate. ### 2. Electric Synapse e.g., gap junctions - In electrical synapses, the cytoplasm of adjacent cells are directly connected by groups of ion channels called gap junctions that allow free movement of ions from the interior of one cell to the interior of the next cell. - By gap junctions the action potentials are transmitted from one smooth muscle fiber to the next in visceral smooth muscle and from one cardiac muscle cell to the next in cardiac muscle. ### 3. Conjoint synapse - The transmission of impulse in these synapses is by both chemical and electrical processes. - They are very rare. ## Compare between chemical and electric synapses |Chemical synapse | Electrical synapse (Gap junction) | |:--------------------------------:|:--------------------------------------:| |A gap two cells without cytoplasmic continuity | Ion channels between two cells | |Unidirectional (from presynaptic to postsynaptic cell) | Bidirectional | |Slow (synaptic delay) | Rapid (no synaptic delay) | |Needs neurotransmitter | No neurotransmitter | |Can be modulated | Can not be modulated | |Sensitive to drugs | Insensitive to drugs | |Excitatory or inhibitory | Excitatory only | |Present in CNS | Present in heart, smooth muscle and CNS| ## Synapses with other cells - When a neuron terminates on a muscle, the connection is properly called a **neuromuscular junction** rather than a synapse. - The contacts between autonomic neurons and smooth and cardiac muscle or glands are less specialized than those between a neuron and skeletal muscle. - The region where the neuron communicates with the effector organ is called the **neuroeffector junction**. ## Synaptic Transmission - An action potential in a presynaptic neuron. - Local potential change - Opening of voltage-gated calcium (Ca 2+) channels in the synaptic knob. - Ca 2+ ion flows into the synaptic knob. - Ca 2+ increases the release of a neurotransmitter from some synaptic vesicles into the synaptic cleft by exocytosis. - The released neurotransmitter diffuses across the cleft and binds with specific protein receptors on the postsynaptic membrane. - These receptors are ligand gated receptor channels. - Binding of neurotransmitter to the receptor-channels causes the channels to open, changing the ion permeability and thus the potential of the postsynaptic neuron (postsynaptic potential, PSP). PSP may be excitatory or inhibitory. - Because the presynaptic terminal releases the neurotransmitter and the membrane of the postsynaptic neuron has receptor-channels for the neurotransmitter, the synapse can operate only in the direction from presynaptic to postsynaptic neuron. - Synaptic transmission takes time, called synaptic delay. - This synaptic delay is usually about 0.5 msec. - In a neural pathway, chains of neurons often must be traversed. - As the number of synapses increases, the total reaction time is prolonged (the time required to respond to a particular event). - Synaptic fatigue is a decline in synaptic transmission after repeated stimulation. - It is caused by: - Depletion of the neurotransmitters. - Downregulation of the postsynaptic receptors. - N.B. it protects neurons in CNS from overexcitation. It can stop the epileptic fits. - Synaptic after discharge is a continuation of discharge of action potential from postsynaptic neuron despite stoppage of presynaptic neuron activity. - It is caused by: - delayed inactivation of the neurotransmitter - a neurotransmitter with a prolonged action. - Synaptic transmission is influenced by chemical changes: - Blood H+ ion concentration: - Increased H+ ion concentration (acidosis) in blood decrease synaptic transmission) - CNS depression (Coma). - Decreased H+ ion concentration (alkalosis) in blood - increase synaptic transmission) - CNS excitation (Convulsion). - Blood O2 level: - Hypoxia → decreases synaptic transmission) - CNS depression (loss of consciousness occurs within 3-5 seconds of stoppage of cerebral blood flow). - Drugs: - Drugs that decrease synaptic transmission e.g., anesthetic drugs, anxiolytic drugs (diazepam), hypnotic drugs (Barbiturates). - They increase the action of GABA. - Drugs that increase synaptic transmission e.g., theophylline, caffeine. - strychnine and tetanus toxin - ( stop the action of glycine). ## Reflex Arc - **Monosynaptic Reflex Arc** - the reflex arc is characterized by simple transmission across one synapse - **Polysynaptic Reflex Arc** - the connection between the sensory neuron and the motor neuron includes two or more synapses. ## Causes of synaptic delay - the time it takes for the neurotransmitter to be released. - The time it takes for the neurotransmitter to act on the receptors on the membrane of the postsynaptic neuron. - Because the minimum time for transmission across one synapse is 0.5 ms, it is possible to determine whether a given reflex pathway is monosynaptic or polysynaptic (contains more than one synapse) by measuring the synaptic delay. ## Types of postsynaptic potential - **Excitatory Postsynaptic Potential (EPSP)** - It is a transient depolarizing potential. - It is excitatory. - It is produced by excitatory neurotransmitter e.g., acetylcholine or glutamate. - It stimulates the development of action potential in postsynaptic neuron. - **Mechanism:** - Opening of sodium channels and sodium influx - Opening of Ca2+ channels and Ca2+ influx - Closure of K+ channels - Increased metabolic rate - **Inhibitory Postsynaptic Potential (IPSP)** - It is a transient hyperpolarizing potential. - It is inhibitory. - It is produced by inhibitory neurotransmitter e.g., glycine, or by presynaptic inhibition. - It decreases the development of action potential in postsynaptic neuron. - Mechanism: - Closure of Na+ channels and inhibition of Na+ influx - Opening of Cl- channels and - Opening of K+ channels and - Decrease metabolic rate - Inhibitory postsynaptic potential can be produced by 2 ways: - **Direct inhibition of postsynaptic neuron**: presynaptic knob is relayed directly on postsynaptic neuron and releases inhibitory neurotransmitter e.g., glycine which induces Cl- influx. - **Indirect or Presynaptic inhibition**: - Inhibitory neurons terminate on presynaptic neuron and inhibits the release of neurotransmitters by preventing Ca2+ influx → exocytosis of neurotransmitter. - This is carried out by prevention of Ca2+ influx via inhibition of opening of voltage gated Ca2+ channels. - This is mediated by inhibiting the development of action potential in presynaptic neuron by increasing Cl- influx or K+ efflux e.g., encephalin (enkephalin) and GABA (Gamma amino butyric acid) neurotransmitters ## Summation of postsynaptic potential - Synaptic potential is a local potential. - It can be graded and summated. - Summation occurs by 3 ways: - **Spatial summation**: produced by simultaneous stimulation of many presynaptic neurons. - **Temporal summation**: produced by repeated successive stimulation of single presynaptic neuron. The interval between 2 impulse should be less than 15 milliseconds (long interval causes decline and fading of postsynaptic potential). - **Temporo-spatial summation**: combination of the above two types. It is produced by repeated successive stimulation of many presynaptic neurons. ## Properties of synaptic transmission - **Forward direction**: from presynaptic to postsynaptic neuron (not the opposite), because neurotransmitters are present in presynaptic nerve terminals. - **Summation**: see previous slides. - **Synaptic delay**: - It is the time required to transmit the signal from presynaptic to postsynaptic neuron. - It is 0.5 millisecond. - It represents the time required to release neurotransmitter, and its binding to receptors on postsynaptic neuron and generation of PSP. - The number of synapse in a reflex can be calculated. - **Synaptic fatigue**: - It is a decline in synaptic transmission after repeated stimulation. - It is caused by: - Depletion of the neurotransmitters. - Downregulation of the postsynaptic receptors. - N.B. it protects neurons in CNS from overexcitation. It can stop the epileptic fits. - **Synaptic after discharge**: - It is a continuation of discharge of action potential from postsynaptic neuron despite stoppage of presynaptic neuron activity. - It is caused by: - delayed inactivation of the neurotransmitter - a neurotransmitter with a prolonged action. ## Clinical Note: Botulinum and Tetanus Toxins - **Clostridia** are gram-positive bacteria. Two varieties, Clostridium tetani and Clostridium botulinum, produce some of the most potent biologic toxins (tetanus toxin and botulinum toxin) known to affect humans. - **Tetanus toxin** blocks the release of glycine and GABA (inhibitory neurotransmitters). As a result, the activity of motor neurons is markedly increased. Clinically, tetanus toxin causes spastic paralysis; the characteristic symptom of "lockjaw" is spasms of the masseter muscle. Tetanus can be prevented by treatment with tetanus toxoid vaccine. - **Botulism** can result from ingestion of contaminated food, or wound infection. - **Botulinum toxins** block acetylcholine release at the neuromuscular junction, leading to flaccid paralysis. - The fatality rate is 5-10%. - An antitoxin is available for treatment, and those who are at risk for respiratory failure are placed on a ventilator. - On the positive side, local injection of small doses of botulinum toxin (botox) has proven to be effective in the treatment of a wide variety of conditions characterized by muscle hyperactivity. Examples include, injection into facial muscles to remove wrinkles. ## Student Activity: True or False? - Electric synapse are more common in CNS than chemical synapse. **F** - Neurotransmitters are stored in the soma of the neurons. **F** - Blocking of voltage gated calcium channels in presynaptic neurons inhibits synaptic transmission. **T** ## References - Barrett KE, Barman SM, Brooks HL, and Yuan JX. (2019). Ganong's Review of Medical Physiology. 26th ed. ebook by McGraw-Hill Education. - Hall JE, and Hall ME. (2021). Guyton and Hall Textbook of Medical Physiology. 14th ed. eBook by Elsevier, Inc. - Sherwood L, (2016). Human Physiology From Cells to Systems. 9th ed. eBook by Nelson Education, Ltd.