12.5 Synapses

12.5 Synapses 1 Expected Learning Outcomes: • Explain how messages are transmitted from one neuron to another. • Give examples of neurotransmitters and neuromodulators and describe their actions. • Explain how stimulation of a postsynaptic cell is stopped. 76 Synapses 2 Synapse—point where an axon terminal meets the next cell (another neuron, gland cell, muscle cell) • For neuron-to-neuron synapses: • Action potential arrives at end of axon of presynaptic neuron • Presynaptic neuron releases neurotransmitter • The postsynaptic neuron responds to it 77 Synaptic Relationships Between Neurons Figure 12.19 78 12.5a The Discovery of Neurotransmitters 1 The synaptic cleft (gap between neurons) was discovered by Ramón y Cajal through histological observations Otto Loewi, in 1921, demonstrated that neurons can communicate by releasing chemicals • Flooded exposed hearts of two frogs with saline • Stimulated vagus nerve of first frog and its heart slowed • Removed saline from first frog and found it slowed heart of second frog • Named it Vagusstoff (“vagus substance”) • Later renamed acetylcholine, the first known neurotransmitter 79 The Discovery of Neurotransmitters 2 Neurotransmitters are released at chemical synapses There are also electrical synapses • Occur between some neurons, neuroglia, and cardiac and single-unit smooth muscle • Gap junctions join adjacent cells; electrical signals spread directly from cell to cell • Advantage—much faster; no delay for release, diffusion, and binding of neurotransmitter • Disadvantage—cannot integrate information 80 12.5b Structure of a Chemical Synapse 1 Synaptic cleft—gap between presynaptic neuron and postsynaptic neuron; typically only 20 um wide • Each neuron has cell-adhesion molecules (CAMs) reaching into the cleft • CAMs link the two neurons together Axon terminal of presynaptic neuron contains synaptic vesicles containing neurotransmitter • Many vesicles are docked on release sites on plasma membrane ready to release neurotransmitter Postsynaptic neuron membrane contains a postsynaptic density of neurotransmitter receptors and ion channels • Ligand-gated ion gates open when neurotransmitters bind to them 81 Synapses 3 Figure 12.20a 82 Synapses 4 Figure 12.20 83 Structure of a Chemical Synapse 2 Figure 12.21 84 12.5c Neurotransmitters and Related Messengers 1 More than 100 neurotransmitters have been identified, most falling into these major chemical categories: • Acetylcholine—formed from acetic acid and choline • Amino acids—include glycine, glutamate, aspartate, and γ-aminobutyric acid (GABA) • Monoamines (biogenic amines)—synthesized from amino acids by removal of the –COOH group but retain the amino group • Examples: the catecholamines epinephrine, norepinephrine, and dopamine; also serotonin, histamine • Purines—adenosine, ATP 85 Neurotransmitters and Related Messengers 2 Major chemical categories of neurotransmitters (continued): • Gases—nitric oxide (N O) and carbon monoxide (C O); synthesized as needed rather than stored in vesicles • Neuropeptides—chains of 2-40 amino acids; cholecystokinin (C C K) and endorphins • Stored in large secretory granules (dense-core vesicles) • Some also function as hormones or neuromodulators 86 Classification of Some Neurotransmitters Figure 12.22 87 12.5d Synaptic Transmission 1 Synapses are variable in their modes of action • Some neurotransmitters are excitatory, others inhibitory, and sometimes a transmitter’s effect differs depending on type of receptor on postsynaptic cell • Some receptors are ligand-gated ion channels; others act through intracellular second messengers • Examples of three kinds of synapses: • Excitatory cholinergic synapse • Inhibitory GABA-ergic synapse • Excitatory adrenergic synapse 88 Synaptic Transmission 2 An excitatory cholinergic synapse • Cholinergic synapse—acetylcholine (ACh) is the neurotransmitter • Steps in synaptic transmission: • Action potential depolarizes the axon terminal, opens voltage-gated Ca 2+ channels • Ca 2+ enters, triggers exocytosis of ACh • ACh diffuses across cleft, binds to postsynaptic receptors • ACh receptors are ligand-gated ion channels that open and allow Na + and K + across the membrane • Entry of Na + causes depolarizing postsynaptic potential • If strong enough, depolarization spreads to the trigger zone, raises the membrane potential up to threshold to trigger an action potential 89 Transmission at a Cholinergic Synapse 1 Figure 12.23 90 Synaptic Transmission 3 An inhibitory GABA-ergic synapse • GABA-ergic synapse—γ-aminobutyric acid (GABA) is the neurotransmitter • Steps in synaptic transmission: • Action potential triggers release of GABA into synaptic cleft • GABA receptors are chloride channels • Cl- entry hyperpolarizes the postsynaptic membrane • Postsynaptic neuron inhibited—less likely to fire action potential 91 Synaptic Transmission 4 An excitatory adrenergic synapse • Adrenergic synapse—norepinephrine (NE) is the neurotransmitter • NE is also called noradrenaline • Monoamines and neuropeptides bind to G-protein coupled receptors on postsynaptic membrane • Activate second-messenger systems such as cyclic AMP (cAMP) • Slower to respond than cholinergic and GABA-ergic synapses • Has advantage of enzyme amplification • Single molecule of NE produces vast numbers of product molecules in cell 92 Transmission at an Adrenergic Synapse Figure 12.24 93 12.5e Cessation of the Signal 1 It is important not only to stimulate a postsynaptic cell but also to turn off the stimulus • Neurotransmitter stays bound to receptor for about 1 ms • If the presynaptic cell continues to release neurotransmitter, one molecule is quickly replaced by another and the postsynaptic cell continues to be stimulated To end the signal: • Presynaptic cell stops releasing neurotransmitter • Neurotransmitter already in synapse is cleared in various ways 94 Cessation of the Signal 2 Clearance of neurotransmitter: • Neurotransmitter degradation—enzyme in synaptic cleft breaks down neurotransmitter • Example: acetylcholinesterase (AChE) breaks ACh down into choline and acetate • Reuptake—neurotransmitter or its breakdown products reabsorbed into axon terminal • Example: choline from ACh recycled to make new ACh • Amino acids and monoamines also reabsorbed, degraded in axon terminal by enzyme monoamine oxidase (MAO)—target of some antidepressant drugs • Diffusion—neurotransmitter or its breakdown products simply away from synapse into nearby ECF 95 Transmission at a Cholinergic Synapse 2 Figure 12.23 96 12.5f Neuromodulators Neuromodulators—chemicals secreted by neurons that have long term effects on groups of neurons • May alter the rate of neurotransmitter synthesis, release, reuptake, or breakdown • May adjust sensitivity of postsynaptic membrane • Nitric oxide (N O) is a simple neuromodulator • Gas that enters postsynaptic cells and activates second messenger pathways (for example, relaxing smooth muscle) • Neuropeptides are chains of amino acids that can act as neuromodulators • Enkephalins and endorphins are neuropeptides that inhibit pain signals in the C N S 97