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Psychology 304: Brain and Behaviour Lecture 14 1 Transmission of Electrochemical Neural Signals and Neuropharmacology 1. How do neurotransmitters generate electrochemical signals in postsynaptic neurons? 2. What mechanisms terminate synaptic transmission? 3. What neurotransmitters have been identified? 2 How do neurotransmitters generate electrochemical signals in postsynaptic neurons? • Neurotransmitters produce signals in postsynaptic neurons by binding to receptors in the postsynaptic membrane. • A neurotransmitter that binds to a receptor is referred to as a ligand. • Most neurotransmitters can bind to a number of receptor subtypes. Among these subtypes are: 3 Ionotropic receptors: When activated by a neurotransmitter, ionotropic receptors cause ligandactivated ion (e.g., Na+, K+, Cl-) channels to open or close, producing an immediate change in potential (EPSP or IPSP) on the postsynaptic membrane. 4 Ionotropic Receptor Activity 5 Metabotropic receptors: When activated by a neurotransmitter, metabotropic receptors cause a subunit of an associated G protein to break away. The subunit either: 1. binds to a ligand-activated ion (e.g., Na+) channel, causing the channel to open or close, producing an immediate change in potential (EPSP or IPSP) on the postsynaptic membrane (Figure A). 2. triggers the synthesis of a second messenger which: (a) binds to a ligand-activated ion channel, causing the channel to open or close, or (b) diffuses through the cytoplasm where it influences the activities of the neuron (Figure B). 6 Figure A Figure B Metabotropic Receptor Activity 7 • If a sufficient number of EPSPs are generated on the postsynaptic membrane by the binding of neurotransmitters to receptors, an action potential will be generated in the postsynaptic neuron. 8 What mechanisms terminate synaptic transmission? • Two mechanisms terminate synaptic transmission: 1. Reuptake. Neurotransmitters are repackaged into vesicles in the cystoplasm. 2. Enzymatic degradation. Example: Acetylcholinestrase. 9 Mechanisms of Neurotransmitter Deactivation 10 What neurotransmitters have been identified? • Four classes of small-molecule neurotransmitters have been identified: 1. Acetylcholine (Ach) Found at neuromuscular synapses, synapses in the autonomic nervous system, and synapses in parts of the central nervous system. 11 Cholinergic neurons: associated with movement, autonomic function, learning, and memory. 2. Monoamine neurotransmitters Found in neurons whose cell bodies are largely located in the brain stem. These neurons tend to have long and highly branched axons with many varicosities from which neurotransmitters are diffusely released. 12 A Branched Axon with Varicosities 13 Subdivided into two groups: (a) Catecholamines: Include dopamine, epinephrine, and norepinephrine. Dopaminergic neurons: associated with movement, attention, reinforcement/reward, verbal learning, and planning. 14 Production of the Catecholamines 15 Adrenergic neurons: associated with attention and arousal. Noradrenergic neurons: associated with attention, arousal, mood, feeding, and sexual behaviour. (b) Indoleamines: Include serotonin (5-HT or 5-hydroxytryptamine) and melatonin. 16 Serotonergic neurons: associated with mood, sleep, feeding, sexual behaviour, and pain. Melatonergic neurons: associated with sleep. 3. Amino acid neurotransmitters Found in fast-acting neurons in the central nervous system. 17 Include glutamate, gamma-aminobutyric acid (GABA), glycine, and aspartate. Of these, the first two are most important. Glutamatergic neurons: the principle excitatory neurotransmitter in the brain and spinal cord; associated with learning and memory. GABA-secreting neurons: the principle inhibitory neurotransmitter in the brain and spinal cord; associated with mood and the “seizure threshold.” 18 4. Soluble gas neurotransmitters Include nitric oxide (NO) and carbon monoxide (CO). Unconventional neurotransmitters. After production in the cytoplasm, they immediately diffuse through the presynaptic cell membrane. Thereafter, the diffuse through the postsynaptic cell membrane and stimulate the production of a second messenger. 19 Function as retrograde transmitters: Diffuse back to the presynaptic neuron and regulate its activity. Little is known about the functions of CO. NO is associated with autonomic activity, learning, and memory. 20 Transmission of Electrochemical Neural Signals and Neuropharmacology 1. How do neurotransmitters generate electrochemical signals in postsynaptic neurons? 2. What mechanisms terminate synaptic transmission? 3. What neurotransmitters have been identified? 21