Neurochemistry Flashcards
What is the role of astrocytes?
Modify synapses
Control potassium ions
Control BBB
Neurotransmitter reuptake
What is the role of oligodendrocytes?
They form the myelin sheath of multiple neurons
What is the role of microglia?
Resident immune cells of the CNS
Engage in phagocytosis
What is the role of ependymal cells?
Ependymal cells line the ventricles
Produce monitor and circulate CSF
What is the role of vascular epithelial cells?
Line blood vessels and form part of the BBB
Where are axons located?
Distal to the cell body
Where are dendrites thpically located?
At the cell body
What are the three main divisions of neurons (polarity)?
Bipolar (olfactory, retinal)
Multipolar (purkinje, pyramidal)
Unipolar (dorsal root ganglion)
What kind of circuits exist in the CNS?
Divergence
Same pathway
Multiple pathways
Convergence
Multiple sources
Single source (multiple synapses between same two neurons)
Reverberating circuit (feedback system)
Parallel after discharge circuit
Where are vesicles stored?
Presynaptic terminal
Where are neurotransmitters made?
Cell body
What are the two forms of axonal transport?
Slow (1-5mm/day)
Fast (200-400mm/day) - neurotransmitters, growth factors, toxins, viruses
What are the three types of synapse?
Axodendritic - axon to dendrite
Axosomatic - axon to cell body
Axoaxonic- axon to axon
What are the two types of receptor?
Ionotropic - ligand-gated ion channels
Metabotropic - GPCRs
How do ligand gated ion channels function?
The binding of a ligand (eg neurotransmitter) changes the shape of the receptor, opening a channel for ions to flow through
Fast effects
Examples: NMDA, AMPA
How do metabotropic receptors function?
Agonist activates receptor
G protein is activated and produces effector
Effector stimulates 2nd messenger synthesis
2nd messenger activates intercellular process
Indirect, slower effect
What is the canonical 2nd messenger?
Cyclic AMP
On what level does a neurotransmitter work?
Single neuron/receptor level
Excitatory - depolarised the membrane and increases the probability of an action potential on that neuron
Inhibitory - hyperpolarises the membrane and decreases the probability of an action potential on that neuron
What would be the effect of serotonin acting on Gi coupled receptor?
Inhibitory
How might excitatory dopamine have an inhibitory effect in a circuit?
Activation of the D1 receptor on a GABA-ergic neuron would increase GABA release at the synapse
GABA would inhibit a downstream glutamatergic neuron
What are the different forms of control of neurotransmitter release?
Activity dependent - neuronal firing rate alters NT concentration at cell body, auto receptors modulate firing rate in turn
Concentration dependent - presynaptic auto receptors can modulate excitability and NT release
Other transmitters - NTs from other terminals activate pre synaptic heteroreceptors (serotonin receptor stimulation at noradrenergic terminals can trigger noradrenaline release)
How might neurotransmitter activity be terminated?
Dissociation from receptor
Receptor internalisation
Synaptic neurotransmitter concentration drops
-diffusion
-reuptake
-catabolism (AChE, MAO)
What type of neurotransmitters are there?
Amino acids - glutamate, GABA, glycine
Gasotransmitters - NO, CO
Monoamines - serotonin, dopamine, noradrenaline, histamine
Trace amines
Peptides - opioids
Purines - ATP, adenosine
Cannabinoids - anandamine, CBD, THC
Acetylcholine
What ion channels are GABA associated with?
Chloride
Potassium
What ion channels are glutamate associated with?
Cations - sodium, potassium, calcium
How do benzodiazepines affect GABA activity?
Modulate GABA receptors to increase the efficacy of GABA
How is glutamate implicated in neurodegeneration?
Excitotoxicity from increased glutamate release causing cell damage and death
What is the function of nicotinic acetylcholine receptors?
Excitatory (ionotropic)
Cell bodies in which areas are dopaminergic?
Substantial nigra
Ventral tegmental area
What receptors does dopamine associate with?
GPCRs
Which dopamine receptor is excitatory?
D1 only
The most widespread
How do amphetamines, cocaine, and methylphenidate (ADHD medication) act?
Inhibit dopamine transporters
Increase synaptic dopamine
What enzyme breaks down extracellular dopamine? (Clue: which inhibitor is used to make L-DOPA more effective?)
COMT
Why is L-DOPA used as treatment instead of dopamine?
Dopamine can’t cross BBB
(Also has effects on heart rate)
Where are the noradrenergic neurons located?
Locus coeruleus
In what ways are noradrenaline and dopamine related?
Structurally similar
NAT transporters are inhibited by same antagonists as DAT transporters
Both broken down intracellularly by MAO
Both broken down extracellularly by COMT
Where are serotonergic neurons located?
Raphe nuclei
What drugs block Serotonin reuptake transporters (SERTs)?
MDMA
Amphetamine
Cocaine
TCAs
SSRIs
Where are histaminergic neurons located?
Tuberomammillary nuclei in the posterior hypothalamus
What does histamine regulate? (Think about where the neurons are located)
Sleep, appetite, body temperature
What neuropsychiatric disorder is histamine implicated in
Schizophrenia
How does caffeine act on dopamine?
Caffeine blocks adenosine receptors
Adenosine unable to block D2 receptors
Increased effect of dopamine
What receptors do heroin and other opiates work on?
Mu opioid receptors
What is the endogenous counterpart of THC?
Anandamide
What is the endogenous counterpart of CBD?
2AG
What do cannabinoids regulate?
Motivation
Pleasure
Feeding behaviour
Where do new experiences effect change in the CNS?
At the synapses
What is the Hebbian theory maxim?
Neurons that fire together wire together
What is the role of NMDA in synaptic plasticity (long term potentiation?)
At resting membrane potential ion flow at NMDA is blocked by Mg2+
Depolarisation of the post synaptic membrane displaces Mg2+
Ca2+ influx activates 2nd massagers
Patterns of this influx influence synaptic plasticity
How are SPECT and PET imaging used in neurochemistry?
Radioactive tagging (Carbon-11) of a ligand that will bind to a particular receptor
Effectively radiotagging each receptor
Allows for quantification if receptors
