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Transcript
Lecture outline of synaptic transmission SYNAPSE Definition : Electrical signals must pass across the specialized gap region between two opposing cell membranes called synapse. SYNAPTIC TRANSMISSION: The process underlying this cell-to- cell transfer of electrical signals. Classification of Synapse: A. Anatomical 1. Between 2 neuron (Neuro-neuro junction ) a. Axosomatic synapse b. Axodenteritic synapse c. Axoaxonic synapse d. Axo-axonic & axodentritic 2. Between neuron & muscle Fiber (Neuromuscular junction) B. Functional Depending upon the basis of transmission of impulses 1. Electrical synapse 2. Chemical synapse 3. Conjoiny (both chemical & electrical) • Synaptic transmission can be classified in at least three ways: 1) Mechanism of transmission Electrical transmission- direct flow of ions from one neuron to another, hence direct influence of electric current from one to another Chemical transmission- neurotransmitter substance released from presynaptic cell, diffuses across synaptic cleft, produced effect on postsynaptic neuron 2) Whether it promotes or suppresses an active electrical response by postsynaptic neuron Excitatory transmission- causes depolarization of postsynaptic neuron, in spiking neurons increases probability of AP, in non-spiking neurons, increases amount of neurotransmitter released Inhibitory transmission- transmission which usually causes hyperpolarization of postsynaptic neuron, decreases probability of AP, in non-spiking neurons decreases neurotransmitter release 3) Whether message is rapidly passed or whether characteristics of postsynaptic cell modulated Classical neurotransmission- signal is rapidly passed to postsynaptic cell, mediated by ionotrophic receptors, mediate rapid electrical response of postsynaptic cell Neuromodulatory transmission- characteristics of postsynaptic cell modulated, mediated by metabotrophic receptors, which initiate biochemical cascade within the postsynaptic neuron Chemical synapse • The transmitter at a chemical synapse can activate either an ionotropic receptor that is itself a channel or a metabotropic receptor that is linked to a G protein. • Ionotropic Receptors are nicotonic ACh receptors and lead to depolarization and action potential excitation resulting in muscle contraction in skeletal muscle Metabotropic receptors are muscarinic ACh receptors which activates release of α GTP+ßý from the heterotrimeric G protein leads to activation of inward K+ channel by ßy eventually memb hyperpolarization and decrease heart rate in cardiac muscle Steps in Chemical Transmission • STEP 1: neurotransmitter are packaged in synaptic vesicles. • STEP 2: an action potential arrives at the preynaptic terminal. • STEP 3:voltage- gated Ca channels open.Ca enters. • STEP 4 :A rise in Ca triggers fusion of synaptic vesicles with presynaptic memb. • STEP 5: Transmitter molecules diffuse across the synaptic cleft and bind to specific receptors on the postsynaptic cell. • STEP 6:Bound receptors activates the post synaptic cell. • STEP 7 :A neurotransmitter breaks down,is taken up by the presynatic or diffuses away from the synapse Neurotransmitters • AMINOACIDS-Gamma-amino butyric acid (GABA), Glutamate (Glu), Glycine (Gly) • Amines; Acetylcholine (ACh), Dopamine (DA), Epinephrine, Histamine, Norepinephrine (NE), Serotonin (5-HT) • Peptides; Cholecystokinin (CCK), Dynorphin, Enkephalins (Enk), Neuropeptide Y, Somatostatin, substance P, Thyroid releasing hormone, Vasoactive intestinal vasopeptide etc. Excitatory Neurotransmitters: • Glutamate – excitatory; – binds to AMPA ionotropic receptors, which open Na+ channels – binds to mGluR metabotropic receptors. – binds to NMDA receptors, which can be both ionotropic and metabotropic because they allow both Na+ and Ca+ to enter the neuron. • Acetylcholine – excitatory; – binds to nicotinic ionotropic receptors, which open Na+ channels – muscarinic metabotropic receptors Inhibitory Neurotransmitters: • GABA – inhibitory – binds to GABA-A ionotropic receptors, which open Cl- channels – Binds to GABA-B metabotropic receptor • Glycine – inhibitory; – binds to ionotropic receptors, which open Cl- channels Glutamate-amino acids • Is a Neurotransmitter of excitatory synapses in majority in CNS. • It is a precursor to GABA which is a major inhibitory NT. • Glutamate has 4 major classes • • • • • • • • G –protein linked metabotropic receptors 3-ionotropic receptors which are AMPA, NMDA and kainate AMPA- amino methyl propionic acid –gated channels found in most excitatory synapses in brain.GluR1-GluR4 NMDA-N- methyl D aspartate-gated channels .they allow entry of ca++ and have slower kinetics because Mg++ blocks the NMDA receptors and when larger depolarization occur Mg++ detaches and opens channel Different from AMPA that both glutamate and glycine bind to open. Other EPSP depolarize memb &Ca++ permeability---- hyperpolarization this lead to hypothesis of role of learning & memory. The ionotropic and metabotropic bind to glutamate but have evolved from diff ancestral protein lines. KAINATE receptors are present at the presynaptic GABAergic terminals and has inhibitory control over GABA transmitter Inhibitory Neurotransmitters/Receptors: • GABA-----brain • Glycine-----spinal cord • They are ionotropic receptors • Open Cl- channel • GABA-A is ionotropic receptor • It opens Cl- channels • GABA-B receptor is metabotropic • Binding of GABA activates GTP binding protein & activation K+ channel &hyperpolarization. Turning Synapses Off • Reuptake. NT is taken back into the synaptic knob of the presynaptic neuron actively. All NTs except acetylcholine use this method. • Acetylcholine ; enzymatic breakdown into inactive fragments (acetylcholinesterase). • Nerve gases used in warfare (e.g., sarin) and the organophosphate insecticides (e.g., parathion) achieve their effects by inhibiting acetylcholinesterase thus allowing ACh to remain active. Atropine is used as an antidote because it blocks ACh receptors. • Spatial summation: Refers to the fact that synapse potential generated at soma and dendrite interact leading to a linear summation. Temporal Summation: The combined amplitude to reach threshold and lead to spiking of cell is called temporal summation or can also occur when same synapse is activated multiple times lead to summation. Neuromuscular transmission: AP at motor nerve terminal → Ach release, across synaptic cleft → Ach + Nicotinic receptor → gNa+ > gK+ depolarization → EPP > Threshold → Muscle AP → Propagation of AP along sarcolemma +T-tubule (local current propagation) → Muscle contraction Presynaptic inhibition and excitation Feed forward excitation and inhibition Reverberating circuit Disinhibition Recurrent inhibition Lateral inhibition Learning objectives Synapse and its classification Types of synaptic transmission Steps involved in chemical transmission Neurotransmitters and its types Summation and its types Neuromuscular transmission and its types