The impact of neuronal activity on functional re-wiring of hippocampal CA1 excitatory neurons.

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It is commonly believed that learning activates a small ensemble of neurons and it induces in these neurons persistent physical/chemical changes. During memory recall these changes enable reactivation of these “engram” neuronal ensembles by relevant cues and hence retrieval of memory. Until now the nature of these persistent changes has remained elusive. It has been proposed that selective increase in connectivity within groups of neurons in a complex circuit results in the emergence of engram neuronal ensembles encoding specific memories. In vivo studies in the neocortex support this theory, showing that learning influences neuronal synaptic structural plasticity. Still, it is not known whether this feature is universal in the mammalian brain or rather specific for brain regions that store information for long-term such as the neocortex. Moreover, it is unclear to what extent the formation of such neuronal ensembles leads to actual changes in connectivity and to what extent such re-wiring is functional to the formation of memories.Here we will use chronic deep-brain two-photon optical imaging to investigate structural synaptic dynamics in hippocampal CA1 pyramidal neurons as neurons get activated either by naturalistic stimuli or by artificial optogenetic stimulation. We will probe synaptic mechanisms that might lead to synaptic structural stabilization and test the extent to which structural synaptic stabilization corresponds to increased synaptic transmission. Finally we will dissect the contribution of intrinsic CA1 excitability versus synaptic activity on structural and functional CA3 to CA1 connectivity.This project proposes to use complementary approaches and cutting-edge technologies to attain a mechanistic explanation for the formation of neuronal ensembles that support learning and memory. The knowledge this work will provide will significantly deepen our understanding of information encoding and recalling in neuronal networks.