Central Neurotransmitters Flashcards
What are the 2 types of synaptic receptors? Give examples
Metabotropic examples= glutamate, muscarinic Ach receptors, GABAB receptors, most serotonin receptors
how is neurotransmitter cleared from the synapse?
Neurotransmitter is cleared from the synapse by:
Enzymatic breakdown
Re-uptake into presynaptic terminal
Diffusion away from synapse
Describe a type of amino acid neurotransmitter, glutamate, how it is made, and its 4 main receptor subtypes.
Glutamine is synthesised in astrocytes (glial cells). Glutaminase converts glutamine into glutamate.
Receptors abundant in cortex, basal ganglia, sensory pathways
4 main receptor subtypes:
NMDA, AMPA & Kainate (ionotropic)
Metabotropic (G-protein coupled)
How is glutamate transported in vesicles?
It joins with VGlut = vesicular glutamate transporter. This eventually releases glutamate which acts on glu receptors to activate neurons.
Why must glutamate release be controlled? How is this done?
Too much glutamate release will cause hyper-excitability of its receptor and cause excitotoxicity and cell death.
Action of glutamate is terminated by uptake into neurons or astrocytes via EAAT, which also recycles excess Glu back into the vesicles.
One of the main receptors that glutamate acts on is NMDA. Describe this receptor.
NMDA receptors (pre- and post synaptic)
Role in synaptic plasticity (hippocampus) + memory
Hyper excitability of NMDA receptors by excess glut linked w epilepsy, depression and stroke.
What are NMDA antagonists? Note- this does not need to be limited to only drugs
Lamotrigine: NMDA antagonist prevents seizures by preventing glutamate excitotoxicity linked w seizures.
Schizophrenia associated w reduction in NMDA stimulation in the frontal cortex
Explain another type of aa transmitter called GABA
Where is it of highest density?
Drugs that modify GABA are used for what?
Give a drug example
Main inhibitory transmitter in CNS (fast), mostly via inhibitory interneurons. Highest density in nigrostriatal system
Drugs that modify GABA developed for anxiety, insomnia, and epilepsy
Vigabatrin inhibits GABA transaminase, anticonvulsant
How is GABA synthesised and deactivated?
Glutamic acid decarboxylase forms GABA from glutamate
GABA reuptake into neurons and astrocytes by specific transporters=main GABA inactivation.
Once in neuron/astrocyte, it is metabolised by GABA transaminase
What are the types of GABA antagonists and what conditions would these be used for?
GAD inhibitor
GABAa receptor antagonist
GABA transaminase inhibitor, eg Vigabatrin
GABA reuptake inhibitor
Used in hyperexcitability conditions such as anxiety, insomnia, seizures
There are 2 types of GABA receptors, GABA A and GABA B. Compare these 2 receptors
What types of drugs activate GABAB?
GABAA receptor= ligand gated Cl- channel for fast postsynaptic inhibition/hyperpolarization
GABAB= metabotropic receptor for slow and prolonged inhibitory signals via G proteins and second messengers.
Baclofen activates GABA B (opioid, GABA release, inhibit glut). Used to treat spasms and epilepsy.
G-Hydroxybutyrate (GHB): partial agonist of GABAB
Describe the Diffuse Modulatory Systems of the Brain (monoamines)
Four systems with common principles:
Small set of neurons which arise from brain stem
Synapses release transmitters into extracellular fluid
Much more widespread effect compared to GABA or glut
What are the 4 main systems of the diffuse modulatory monoamines in the brain?
Where do they originate from?
Noradrenergic: from the Locus Coeruleus
Serotonergic: Raphe nuclei
Dopaminergic: Substantia nigra, Ventral tegmental Area
Cholinergic: Basal Forebrain and Brainstem complexes
Describe Noradrenaline, one of the main types of monoamine neurotransmitter.
Where does it project to?
Involved in: Arousal, wakefulness
Mood (low NA in depressed)
Blood pressure
Gives the ‘high’ in addiction/gambling
Cell bodies for NAergic neurones are in the LC, and projects to the cortex, amygdyla (emotion), hypothalamus, SC and cerebellum
Describe the synthesis pathway for dopamine and NA
What are the different dopaminergic pathways?
Nigrostriatal: Substantia nigra projects to the striatum to control/initiate movement
Mesocorticolimbic: transports DA from VTA to the n.accumbens, amygdala and frontal cortex. Linked w reward, schizophrenia and memory consolidation
Tuberohypophyseal: DA release from hypothalamus inhibits prolactin release
How are DA levels regulated?
Neuronal uptake via DA receptors, then DA broken down by MOAb
D2 receptors are found pre AND post synaptically. Pre synaptically D2 inhibits and thus regulates the release of DA.
Describe another monoamine, 5-HT
What are the different actions of Serotonin/ 5-HT on different regions of the brain?
AKA serotonin
Distribution of 5-HT neurons resembles that of NA. Cell bodies from the raphe nucleus projects to different regions of the brain.
Outline how serotonin is formed
How are 5HT levels regulated?
Neuronal uptake via 5-HT receptors, then 5-HT broken down by MOA
Presynaptic 5-HT1d receptors inhibits and thus regulates 5-HT release.
What are autoreceptors? Give the autoreceptors for DA, 5HT, NA
Transportersusually take the neurotransmitter back up into the pre-synaptic terminal. Give a list of transporters for the diffreent types of aa neurotransmitters
