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