Subfield-Specific Interneuron Circuits Govern the Hippocampal Response to Novelty

Abstract

The hippocampus is the brain’s center for episodic memories about our life. Its individual subregions, the dentate gyrus (DG), CA3, 2, and 1, are differentially involved in the encoding and recall of episodic memories. While hippocampal principal cells represent episodic features, such as movement, space, and context, much less in known about the role of various types of GABAergic inhibitory interneurons (INs) in regulating information processing. Here, we performed two-photon calcium imaging of hippocampal parvalbumin (PV)- and somatostatin (SOM)-expressing INs in the DG, CA3, 2 and 1 of head-fixed mice to define their activity dynamics during foraging in virtual environments. Throughout hippocampal subfields, both IN-types showed moderate spatial tuning. PV-INs increased their activity with running-speed and reduced it in novel environments. Among SOM-INs, we observed a dichotomy: CA1-3 SOM-INs behaved similar to PV-INs, but in the DG, their activity increased during immobility and in novel environments. These data indicate a new form of dynamic routing of information flow through hippocampal subfields tailored to cognitive demands and controlled by distinct inhibitory circuits.