Plasticity

Short- and long term plasticity are defined by the different time scales on which they persist, where the former typically range from a few milliseconds to seconds or minutes, while the latter persists over hours or days. Short term plasticity is typically related to the intrinsic signal processing of microcircuits, while long term plasticity is associated with permanent changes in synaptic strength related to learning and memory. It has been a long standing interest of the LNMC to understand the principles of both short- and long term synaptic plasticity. 

Short-term plasticity is immediately evident when a synapse between a pair of neurons is activated. It is generally frequency dependent and is jointly studied with connectivity analyses of microcircuits [2].

Evoking long-term plasticity requires more demanding experimental protocols as they have to be controlled and monitored over long periods of time. We have already shown that the spike timing of pre- and post synaptic neurons determine type of plasticity – potentiation or depression along with the degree of plasticity [1]. This can be studied in a phenomenon called spike-timing dependent plasticity (STDP). We are currrently exploring the rules of plasticity with a background of neuronal activity and find that the network context is of primary importance for synaptic plasticity. In particular, well established STDP rules are modulated by the whole network activity in a time-dependent manner.

Approach

The gold-standard technique for recording sub-threshold activity is whole-cell patch-clamp recording. Either short- and long-term plasticity can be studied through paired recordings (ie: connected pairs of neurons), or by the combination of whole-cell recordings with extra-cellular electrical stimulation. Extra-cellular electrical stimulation can be performed locally through a single electrode, or mesoscopically using a micro-elecrode array (MEA) which allow the stimulation of individual cortical layers or the whole cortical column.

Short-term plasticity: In the connectivity analyses of microcircuits in LNMC we routinely use multi-patch electrophysiology to examine the post-synaptic response to pre-synaptic trains of activity, thus mapping the short term plasticity associated with different types of synaptic connections. Furthermore, we are also investigating the effects on short-term synaptic plasticity in relation to autism and/or neuromodulation.


STDP and Network activity:  We are currently investigating the role of STDP in the context of network activity using MEA stimulation in combination with patch clamp recordings.

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