Vasoactive Intestinal Polypeptide-Expressing Interneurons in the Hippocampus Support Goal-Oriented Spatial Learning

The hippocampus is a critical brain structure that allows orientation in space. Specifically, this function has been assigned to so-called place cells whose activity increases when animal enters a specific location in environment. Place cells are excitatory cells and their activity is under control of inhibitory interneurons (INs). Interestingly INs can be under control of other interneurons, so-called disinhibitory interneurons.

Losonczy’s group was interested how these canonical disinhibitory circuit motifs contribute to network operations supporting spatial navigation and learning in the hippocampus. The group focused on disinhibitory interneurons that express vasoactive intestinal polypeptide (VIP).

Using chronic two-photon calcium imaging in mice performing random foraging or goal-oriented learning tasks, the researchers found that VIP-INs in hippocampal area CA1 form two functional subpopulations defined by their modulation by behavioral states and task demands.

Optogenetic manipulations of VIP-INs and computational modeling further show that VIP-INs mediated disinhibition is necessary for goal-directed learning and related reorganization of hippocampal pyramidal cell population dynamics. The results of this research demonstrate that disinhibitory circuits in the hippocampus play an active role in supporting spatial orientation.

All imaging used in this paper was conducted using a two-photon microscope equipped with an 8 kHz resonant scanner (Bruker, Billerica, MA). Calcium imaging was done simultaneously with photostimulation via LED (620 nm) coupled to the two-photon microscope. To avoid saturating the PMTs during recording sessions, custom-made electronics triggered light pulses on the fly back time of the galvanometer when there was no image acquisition.