Organization and Plasticity of Inhibition in Hippocampal Recurrent Circuits

Abstract

Excitatory-inhibitory interactions structure recurrent network dynamics for efficient cortical computations. In the CA3 area of the hippocampus, recurrent circuit dynamics, including experience-induced plasticity at excitatory synapses, are thought to play a key role in episodic memory encoding and consolidation via rapid generation and flexible selection of neural ensembles. However, in vivo activity of identified inhibitory motifs supporting this recurrent circuitry has remained largely inaccessible, and it is unknown whether CA3 inhibition is also modifiable upon experience. Here we use large-scale, 3-dimensional calcium imaging and retrospective molecular identification in the mouse hippocampus to obtain the first comprehensive description of molecularly-identified CA3 interneuron dynamics during both spatial navigation and sharp-wave ripple (SWR)-associated memory consolidation. Our results uncover subtype-specific dynamics during behaviorally distinct brain-states. Our data also demonstrate predictive, reflective, and experience-driven plastic recruitment of specific inhibitory motifs during SWR-related memory reactivation. Together these results assign active roles for inhibitory circuits in coordinating operations and plasticity in hippocampal recurrent circuits.