Neuromodulation Flashcards
Name 4 diffuse modulatory systems
dopamine
serotonin
noradrenaline
acetylcholine
Describe the features of an ionotropic receptor
ligand gated ion channels direct transmission flux ions directly excitatory or inhibitory fast transmission
Describe the features of a metabotropic receptor
signals not sent directly but through G coupled proteins which trigger a series of intracellular events
indirectly lead to ion flux
slower but prolonged information transmission
hundreds of G protein coupled receptor
Describe the activation of metabotropic receptors
transmitter binds to extracellular domain of receptor
change in intracellular domain
binding triggers G protein uncoupling
signal is transducer across the cell membrane
Describe the cascade of signal transduction to a metabotropic receptor
G protein effector protein second messenger kinase enzyme channel activation/gene transcription
Describe the process of G protein uncoupling
at rest G protein is bound to GDP
on the binding of the ligand to the receptor GDP is switched for GTP
the G protein splits
the parts diffuse separately
individually stimulate activity of other effector proteins
the recomplexes to repeat the cycle
What are the two G protein coupled effector systems?
a subunits - around 20
bg complexes - 5b and 12g
What are the types of G protein a subunits and what do they do?
Gs; stimulates adenylyl cyclase
Gi; inhibits adenylyl cyclase
Gg; stimulates phospholipase C
What do the bg complexes of?
activate K+ channels directly via the G protein gates ion channel
What is the function of phosphatases?
to regulate and maintain the activity of proteins, phosphorylation gated channels open and close dependent on phosphorylation
What do presynaptic receptors do?
change the amount of neurotransmitter released
How are G protein signals amplified?
one transmitter bound receptor can uncouple multiple G proteins
What do auto receptors do?
regulate the release of transmitter by modulating its synthesis, storage or reuptake
What do heteroreceptors do?
axoaxonic synapses or extrasynaptics modulate the release of another transmitter
What do postsynaptic receptors do?
change the firing pattern or activity of a neurotransmitter
How do postsynaptic receptors firstly change firing rate?
by acting on the ligand gated channels
How do postsynaptic receptors indirectly change firing rate?
by activating metabotropic receptors leading to G protein gated or phosphorylation gated channels opening
Name the types of presynaptic receptor
autoreceptors
heteroreceptors
Name the types of metabotropic receptor
metabotropic glutamate GABAb muscarinic acetylcholine dopamine noradrenergic adrenergic serotonin neuropeptide
Describe the synthesis of neuropeptides
gene transcribed from mRNA translated to protein transported though golgi to vesicles chopped into neuropeptides multiple neuropeptides can be synthesised from propeptides
How are hippocampal theta waves controlled?
by the neuromodulatory acetylcholine release in the hippocampus
What is the function of scopolamine?
its an antagonist of muscarinic acetylcholine receptors
disrupts hippocampal theta waves
disrupts learning and memory
Name two agonists of the opioidergic system
morphine and heroin
Name two antagonists of the opioidergic system
naloxone and nalteroxe
What are the roles of the opioidergic system?
analgesia; release of endogenous opioids inhibits pain signals
relaxation; regulates noradrenaline release
What are some subjective effects of opiate use?
euphoria and intense rush; heroin due to route of administration
tolerance/dependence; increasing doses required for analgesic response
What does sustained release of noradrenaline cause?
activation of the autonomic nervous system
What causes tolerance to opiates?
chronic activation of the opioid receptors
What does acute morphine do?
acutely inhibits firing of LC neurons through the Gi pathway
What does chronic treatment of opioids cause?
locus coerleus neurons return to their normal firing rates
Gs pathway up regulates to match Gi
What does opioid withdrawal cause?
dramatic increase in locus coerleus firing (in absence of Gi inhibition, Gs is hypersensitive)
What is cAMP?
cyclic adenosine monophosphate; a second messenger
What does protein kinase A (PKA) do?
activates the Na+ channel and depolarises the neuron
How does the Gs pathway affect the second messenger cascade?
it increases PKA and depolarises the neuron
How does the Gi pathway affect the second messenger system?
decreases PKA and inhibits the neuron
What do the Gbg subunit on Gi do?
activates the K+ channel causing more inhibition
What compensatory changes take place in the up regulation of the cAMP pathway?
increased expression of adenylyl cyclases
increased PKA expression
decreased PKA degradation
