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NEUROCHEMISTRY
Key PointsNeuron-to-neuron or neuron-to-effector organ interactionsUnderstand the structure and function of the synapsePresynaptic release and postsynaptic receptorsKnowledge of the major types of neurotransmitter/neuromodulatorBasic understanding of EPSPs and IPSPsDifferent types of signalling - ionotropic and metabotropic receptors, second messengersColocalization of neurotransmitters/neuromodulatorsInactivation/degradation/re-uptake of neurotransmitters after releaseGlial cells have an important role to play in synaptic transmissionSome knowledge of distribution of neuroactive substances and relation to certain CNS pathways
Suggested ReadingNolte (4th Ed), pgs 12-23, 172-190Fitzgerald, pgs 41-46Crossman and Neary, pgs 1-2, 19-22
The neuron
myelin
The chemical synapsePresynaptic and postsynaptic components
Synaptic cleftRelease of neurotransmitters and neuromodulators that bind to receptorsExcitatory or inhibitory effectsLocation 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-acidsglutamate, GABA (γ-aminobutyric acid), glycine
MonoaminesAcetylcholine, serotonin, dopamine, noradrenaline, adrenaline
Neuropeptideseg 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
Last Slide