NEUROCHEMISTRY Key Points Neuron-to-neuron or neuron-to-effector organ interactions Understand the structure and function of the synapse Presynaptic release and postsynaptic receptors Knowledge of the major types of neurotransmitter/neuromodulator Basic understanding of EPSPs and IPSPs Different types of signalling - ionotropic and metabotropic receptors, second messengers Colocalization of neurotransmitters/neuromodulators Inactivation/degradation/re-uptake of neurotransmitters after release Glial cells have an important role to play in synaptic transmission Some knowledge of distribution of neuroactive substances and relation to certain CNS pathways Suggested Reading Nolte (4th Ed), pgs 12-23, Fitzgerald, pgs Crossman and Neary, pgs 1-2, 19-22

The neuron myelin

The chemical synapse Presynaptic and postsynaptic components Synaptic cleft Release of neurotransmitters and neuromodulators that bind to receptors Excitatory or inhibitory effects Location of synapses on neurons

Synthesis Presence and release from presynaptic site Bind to postsynaptic receptor Effect change in postsynaptic cell Inactivation (removal, inactivation or degradation – by neurons or glia) SITES OF DRUG ACTION

Neurotransmitters/neuromodulators Synaptic transmission can be rapid and point-to-point, or slow and often diffuse Amino-acids glutamate, GABA (γ-aminobutyric acid), glycine Monoamines Acetylcholine, serotonin, dopamine, noradrenaline, adrenaline Neuropeptides eg substance P, enkephalins, endorphins, somatostatin, cholecystokinin (CCK), vasoactive polypeptide (VIP), neuropeptide Y etc

Ionotropic Involves transmitter gated ion channels Fast synapses (classical synapses) – usually point-to- point Fast time course, EPSP or IPSP Metabotropic Activate G proteins and second messengers Slow synapses –diffuse, long- acting effects often involve metabotropic receptors

Schematic view of the location and distribution of excitatory and inhibitory synapses on a neuron Excitatory Inhibitory

Brain distribution and relation to anatomical pathways Distribution of neurotransmitter/neuromodulator versus distribution of receptor Studied using biochemistry, immunohistochemistry, in situ hybridization, receptor binding, physiology/pharmacology, modern neuroimaging techniques in humans Changes with age and in disease Changes in the expression of neurotransmitters and their receptors with age Changes associated with some psychiatric disorders Changes associated with neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease Use of drugs/pharmacotherapy

Cholinergic pathways in human brain

Astrocytes and synaptic function

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