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Neuromodulation of neural plasticity: Mechanisms and implications for brain function (Ole Paulsen)

Supervisor: Ole Paulsen

Our group is interested in the rules and roles of synaptic plasticity in learning and memory and during development. Using patch-clamp and multielectrode recordings combined with optogenetics, we want to understand how changes in synaptic weights shape cortical circuits and how these changes can guide subsequent behaviour. Recently, it has emerged that the rules of synaptic plasticity are not constant, but are brain state dependent. This occurs partly because neuronal patterns of activity are different in different brain states, leading to the concept of spike pattern-dependent synaptic plasticity (Rodriguez-Moreno et al., 2013), but also because different brain states are associated with activity in distinct neuromodulatory inputs, such as cholinergic and dopaminergic projections. We have recently uncovered that cholinergic and dopaminergic inputs into the hippocampus can bias plasticity in opposite directions, and, surprisingly, that these effects can be retroactive, e.g. dopamine can convert synaptic depression into potentiation when applied after the induction of plasticity (Brzosko et al., 2015). This is likely to have important consequences for memory formation. We hypothesise that dopamine, as a reward signal, changes the synaptic weights making the animal more likely to seek rewarded locations. A PhD project in this area could combine a basic mechanistic understanding of neuromodulation of plasticity with elucidating the behavioural consequences of this plasticity (Shipton et al., 2014). Techniques would include electrophysiological recording and optogenetics, and depending on the particular project, either sensory stimulation or behavioural memory testing. The research should lead to new insights into the mechanisms and functions of synaptic plasticity in the brain.

Relevant references

Brzosko Z, Schultz W and Paulsen O (2015) Retroactive modulation of spike timing-dependent plasticity by dopamine. eLife 4:e09685.

Rodríguez-Moreno A, González-Rueda A, Banerjee A, Upton AL, Craig MT and Paulsen O (2013) Presynaptic self-depression at developing neocortical synapses. Neuron 77: 35-42.

Shipton OA, El-Gaby M, Apergis-Schoute J, Deisseroth K, Bannerman DM, Paulsen O and Kohl MM (2014) Left-right dissociation of hippocampal memory processes in mice. Proc Natl Acad Sci USA 111: 15238-15243.

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