Central Synapses Flashcards
The synaptic terminals of exc. and inh. neurons can be distinguished by their…
Ultrastructure.
Type I synapses have what effect?
Excitatatory.
Type II synapses have what effect?
Inhibitory.
Type I synapse structure:
Round vesicles, electron dense regions on presynaptic (active zones) and postsynaptic (postsynaptic density) membranes. Postsynaptic density even larger. Gives asymmetric appearance.
Type II synapse structure:
Oval/flattened vesicles, less obvious pre and postsynaptic specialisations. More symmetric.
Where are excitatory synapses?
Mostly axodendritic, occuring mostly on dendritic spines.
Where are inhibitory synapses?
Dendritic shafts, the cell body, and axon initial segment.
How is fast excitatory transmission terminated?
Glu diffuses out of cleft, reuptake by astrocytes, convert to glutamine. Glutamine taken up by neurons.
Why does GABAa opening generally lead to hyperpolarisation?
Cl- equilibrium potential negative to RMP.
How is GABA removed from extracellular fluid?
GABA transporters (GATs).
How do benzodiazapines act on GABAa receptors?
Increase the total conduction of Cl- across the neuronal cell membrane when GABA is already bound to its receptor.
The decision of whether AP depends on spatial and temporal summation of excitatory and inhibitory inputs at the …
Axon initial segment.
How does reduction of cAMP lead to reduced excitability?
Less activation of protein kinase A (PKA), decreased ion channel phosphorylation, reduces their activity.
What presynaptic GluR acts as an autoreceptor?
mGluR2.
How does presynaptic mGluR2 exert its effect?
Inhibition of adenylyl cyclase, reduction of cAMP, suppressed Ca2+ channel activity, less Glu release.
mGluR2 acts as a negative feedback mechanism to…
Protect neurons from excitotoxicity.
How do presynaptic (metabotropic) GABAb receptors exert their autoreceptor effect?
Inhibition of adenylyl cyclase, reduced cAMP etc.
How do postsynaptic (metabotropic) GABAb receptors exert their effect?
Activate GIRKs, hyperpolarises.
Where are postsynaptic GABAb found?
On motor neurons in the spinal cord.
What drug highlights the role of postsynaptic GABAb receptors?
Baclofen, GABAb agonist, used as muscle relaxant in spasticity treatment.
Why does signalling via metabotropic receptors take onger?
Trigger a second messenger response that requires multiple proteins to interact with each other in a sequential order.
Inhibitory mAChRs are coupled to what G protein? Postsynaptic reduction of cAMP.
Gi.
Where are M2 (Gi coupled) mAChRs? What do they do?
Found in heart, mediate bradycardia.
Where are M4 (Gi coupled) mAChRs? What do they do?
CNS, particularly striatum, regulate dopaminergic transmission, implicated in PD.
Excitatory mAChRs are coupled to what G protein?
Gq.
How do Gq coupled (excitatory) mAChRs exert their effect?
Activate phospholipase C (PLC), increase IP3 and DAG, raise intracellular Ca2+, increase excitability.
Where are the M1 (Gq coupled) mAChRs? What do they do?
Found in CNS, involved in learning, memory and cognition.
Where are the M3 (Gq coupled) mAChRs? What do they do?
Found in smooth muscle and glands, promote bronchoconstriction and glandular secretion.
What Ms are Gi coupled AChRs vs Gq coupled.
M2, M4 vs M1, M3.
What increases probability of neuronal firing (intrinsic plasticity)?
Residual Ca2+ in synaptic terminal.
What decreases probability of neuronal firing (intrinsic plasticity)?
Vesicle fusion reducing number of possible release sites.
Where is facilitation likely to occur? Why?
Synapses that show low initial probability of release. Effect of residual Ca2+ dominates.
Why STP not obvious at NMJ?
Basal EPP exceeds AP threshold by large margin. Reliably evoke APs even at high spike frequencies.
Who showed LTP at Schaffer collateral synapse?
Bliss and Lomo, 1973.
LTP mechanism:
Depolarisation causes removal of Mg2+ block in NMDARs, allows Ca2+ influx. Activates calcium/calmodulin-dependent kinase II, phosphorylates AMPA channels to increase conductance and favours insertion of new ones in membrane.
Structure of electrical synapses:
Formed by two hemichannels that connect across intercellular space, gap junctions.
Where do electrical synapses occur? And one example.
Mostly between the dendrites of neurons of the same subtype, for example bipolar cell electrical coupling in the CNS.
Why do electrical synapses occur mostly between the dendrites of neurons of the same subtype?
Impedance matching. Same subtype similar size.
What do gap junctions allow?
Small molecules and ions to pass easily from the cytosol of one cell directly into the cytosol of the next. In both directions so bidirectional communication. Also rapid, no delay inherent in chemical synapses.
Where in the body are electrical synapses? Why?
Cardiac muscle and smooth muscle. Because there important to co-ordinate the activity of a large number of cells.
Why is the synaptic cleft of the NMj larger than many central synapses?
To accomadate the release of a large amount of ACh after a single AP. Several micrometres. Cs, 20-40 nanometres. CS designed for intricate signalling and integration that occurs in the CNS.
