Role of neuromodulation in presynaptic plasticity

Action potentials form a part of neuronal signalling whereby an increase in membrane potential over a certain threshold sends electrical signals propagating along the axonal membrane. Much attention has been given to the effects of an action potential on the pre-synaptic terminal while overlooking the implications of fluctuation in the membrane potential immediately before the action potential. Such graded component of action potential has been shown to influence the release of neurotransmitter-containing vesicles at pre-synaptic terminals in both the cortex and hippocampus.
Using dynamic clamp, the impact of serotonin, an important neuromodulator, on the rate of change of sub-threshold membrane potential and on subsequent post-synaptic response will be investigated. The timings and location of neuromodulator release are likely to have different effects on analog-digital signalling. This differential effect will be characterised using light-activated compounds to reliably stimulate distinctive temporal and spatial patterns of serotonin release.
Once the cellular and sub-cellular effects have been characterised, optogenetic approaches will be used to study network activity whereby multiple neurons are monitored simultaneously. The same approaches will be used in order to tag specific markers in neural stem cells and follow them through differential and maturation that allow us to study their effects on the electrical properties of the local neuronal network.