Neuromodulation 1 Flashcards
What is neurotransmission?
Primary neurotranmission = Glutamate and GABA, which act as primary neurotransmitters. Directly mediate the transmission of information between neurons either via activation (excitation, EPSPs) or inactivation (inihibition, IPSPs) of post-synaptic targets.
What is neuromodulation?
Act at their receptor and change the property of the neuron that they’re communicating with. Rather than carrying primary info, they change properties of the neuron. e.g. dopamine, serotonin, noradrenaline, and acetylcholine.
What are the diffuse modulatory systems?
Specific populations of neurons that project diffusely and modulate the activity of Glutamate and GABA neurons in their target areas.
Dopamine (movement /reward), Serotonin (sleep /mood), Noradrenaline (arousal / attention), and Acetylcholine (attention / learning).
What is an Ionotropic receptor?
Has ligand-gated ion channels - ligand is the neurotransmitter, ion channels are made up of sub-unit proteins that when the ligand binds, that pore opens and they are able to flux either positive (will depolarise neuron) or negative (will inhibit). Direct transmission – when activated, get flux of neurons directly through them. Can either be excitatory or inhibitory. Has fast transmission of information.
What is a Metabotropic receptor?
Otherwise known as g protein coupled receptors: receptor activates the g protein. Modulatory rather than direct transmission, as ion flux is indirect (either by protein or phosphorylation). Slower because is not an immediate effect of opening the channel. In being slower, has the potential for the signal to be amplified.
How are metabotropic receptors activated?
From activation of the receptor, a signal transduction cascade occurs within the cell, which leads to receptor activation. G-protein activates effector protein, which activates a second messenger, which activate kinase, which leads to either channel activation by phosphorylation or gene transcription.
How are metabotropic receptors activated? (continued)
Transmitter (ligand) binds to extracellular domain of receptor. If right receptor then conformational change in intracellular domain. Binding triggers uncoupling of a heteromeric G protein on the intracellular surface. The signal is transduced across the cell membrane.
What happens when a G protein is activated?
GTP–binding proteins composed of three
Subunits – α, β and γ
1) in resting state the G protein is bound to GDP
2) on binding of a ligand to the receptor the GDP is switched for a GTP and the G protein splits
3) the α subunit and βγ complex diffuse separately
through the membrane
4) They individually stimulate activity of other
effector proteins
5) α subunits have intrinsic GTP-GDP enzymatic activity - the signal to be transient. The conversion of GTP to GDP switches off its activity
6) The G protein recomplexes ready for activation
by a new ligand binding to receptor.
What are G protein-coupled effector systems?
In comparison to the numbers of receptors there are relatively few G proteins. α subunits (~20) Gs stimulates adenylyl cyclase Gi inhibits adenylyl cyclase Gq stimulates phospholipase C βγ complexes (5 β and 12 γ) Activate K+ channels directly (G protein gated ion channel). Muscarinic ACh receptors in the heart and the GABA(B)receptor act by βγ coupling to K+ channels (Relatively fast acting local effect).
What are second messenger cascades?
Gs and Gi have opposing effects on adenylyl cyclase, thus stimulating or
inhibiting the synthesis of cAMP and the subsequent activation of protein
kinase A (PKA). Beta-adrenergic receptor couples to Gs – leads to stimulation of adenylyl cyclase
Alpha2-adrenergic receptor couples to Gi – leads to inhibition of adenylyl cyclase.
What is kinases and phosphatases?
Activity of many proteins regulated by their phosphorylation state. Maintenance of phosphorylation state an important level of control. e.g. phosphorylation gated channels - influence membrane potentials to cause or block the cell from firing.
What is involved in the amplification of G protein signals?
G protein signalling provides a method of amplifying signals between neurons. One transmitter bound receptor
can uncouple multiple G proteins. The signal can be amplified at every stage. What begins as a weak signal at the synapse can cause an amplified response in the postsynaptic cell.
How is there modulation in presynaptic receptors?
Change the amount of transmitter released. Autoreceptors = regulate release of transmitter by modulating its synthesis, storage, release or reuptake, e.g. presynaptic dopamine receptor activation. Heteroreceptors = axoaxonic synapses or extrasynaptic, modulate the release of another transmitter (overspill between synapses), e.g. Nicotinic receptors - ligand gated ion channel flux Ca2+ activation would lead to release of transmitter.
How is there modulation in postsynaptic receptors?
Change firing pattern or activity. Increase or decrease rate of cell firing. Either: directly by action at ligand gated ion channels, or indirectly by activation of metabotropic receptors leading to G protein-gated or phosphorylation-gated channel opening. Is either excitatory or inhibitory, depending on receptor, G protein, channels. Signal transduction & second messenger cascades can also lead to long term synaptic changes.
What are neuropeptides?
Another kind of neurotransmitter - vary in their methods of synthesis (cell body) and release from small molecule transmitters. Short polypeptide chains. Produced by cleavage of pro peptides synthesised directly from mRNA.
