Neuropharmacology - Neurotransmission Flashcards
(20 cards)
Cell types in the brain
neurons, astorycytes, microglia, endothelial cells and pericytes
Neuron structure
Axon, dendrites, cell body and nucleus.
Physiological role of astrocytes in brain function
Releases and takes up NTC (glutamate) Expresses receptors (NMDA) Regulates synaptic transmission Conducts electrical events via gap junctions Memory formation Produces and releases neurotrophins
Roles of astrocytes in brain pathology
Scar formation which impairs the reformation of axons
Immune activation through antigen presentation
Types of astrocytes
Protoplasmic
Interlaminar
Fibrous
Polarised
Protoplasmic astrocytes
- Most common type
- Resides in layers 2-6 of cortex
- Has non overlapping GFAP positive processes (domain organisation)
-Astrocyte domains may cover 10 nerve cell bodies, and 5 blood vessels therefore having an important position for coordination (e.g regulate blood flow in response to increased synaptic transmission)
Fibrous astrocytes
- Found in grey and white matter
- Processes intermingle ( does not form domain structure)
- Supportive role rather than information processing. Responds to mechanical injury e.g stroke (produces scar tissue)
Gliotransmission
Process where transmitters are released from astrocytes and act on neurons
Glioneural function units
Thought that memories are encoded in astorcyte networks
Astrocytic adenosine release induces sleep via caffeine sensitive receptors
Microglia
Resident macrophages of the brain
Surveys the brain microenvironment
Sensitive to brain perturbations
Mediates brain immune response
Phagocytose plaques, debris in Alzheimers disease?
May modulate neurotransmission
Involved in the sculpting of the brain during development and modulates synaptic transmission.
Pericytes and brain endothelial cells
Pericytes enclose cells within the brain capillaries and maintain the BBB
In Neurological disorders such as alzheimers and stroke, the BBB and NV unit are compromised .
- Invasion of Hb, and T cells across the BBB. These compounds are toxic to neurons?
Molecular targets for brain targeting drugs
Enzymes involved with NTC formation or degradation Structural proteins Ion channels NTC reuptake proteins NTC receptors Transducer proteins, GPCR
Synaptic transmission
Neurons can form synapses with thousands of other neurons. Few of these synapses convey info through NTC (1st messenger and Ca2+ dependant).
Diffuse across synaptic cleft, binds onto NTC receptor on PS membrane.
Binding leads to the formation of 2ndary messengers resulting in the excitation of the neuron or inhibition
Termination of NTC activity
Reuptake and/or metabolism
Properties of NTC and examples + classes
Fast effects Monoamines: Serotonin, NA, dopamine Aminoacids: GABA, glutamate, glycine Neuropeptides Neuromodulators Other: Acetylcholine
Pathology affecting GABA transmission
Dampening of excitation leads to seizures
Strychnine
Glycine receptor antagonist.
- Blocks Cl- ligand gated channels, preventing the inhibitory effects of glycine on the postsynaptic neuron
- Therefore, action potentials are triggered with lower levels of excitatory neurotransmitters.
Neuromodulators vS NTC
NMs have slower pre and post synaptic responses and are released by nerve cells and astrocytes.
Neurotrophic factors
Released by non neuronal cells (astro + microglia) and neurons.
- Works over long time scales
- Acts on tyrosine kinase receptors to mediate growth, morphology, functional properties, survival promoting effects across the Nervous system.
NTC properties
Fast acting (Ion channel action) - GABA,glutamate, glycine Slow- GPCR (Dopamine , neuropeptides, GABA, acetylcholine.
Can have both fast and slow actions depending on the receptor they act on.