Two to Tango: Joint dynamics of Excitatory and Inhibitory Synapses during Memory Formation

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Learning and memory have been traditionally associated to the plasticity of glutamatergic synapses. Recent experimental evidence indicates that GABAergic synaptic strength can also be modified in an experience-dependent manner. Yet, the specific role of inhibitory plasticity in the formation of memories is not well understood. A recent theoretical analysis suggests that the formation and long-term storage of memories require a tight co-orchestration of excitatory and inhibitory plasticity in a multi-stage process. In particular, inhibitory synapses may not only play a role in controlling excitatory plasticity during memory encoding, but also in supporting long-term memory storage as they have a storage capacity much larger than the excitatory synapses. Here, we propose to test this hypothesis by combining chronic in vivo imaging of excitatory and inhibitory synapses in the auditory cortex of mice in the context of an associative memory task, with theoretical modeling of network dynamics. Furthermore, we plan to interfere specifically with molecular mechanisms essential for the potentiation of excitatory synapses to disentangle the interdependencies of the plasticity of excitatory and inhibitory synapses during learning. This interplay of experiments and theoretical modeling will provide new insight on how plasticity of excitatory and inhibitory circuits participate in learning and memory processes, probably the most fundamental functions of our brains.