Investigation of Novel Hippocampal Cell Population’s Modulation over Spatial Memory
The supramammillary area (SuM) is a ventral hypothalamic nucleus with direct connections to the hippocampus. The SuM has been shown to modulate hippocampal theta rhythm—a measure of synchrony between hippocampal regions—and other processes such as cognition, learning, and memory. We recently identified a novel population of inhibitory hippocampal-based neurons projecting to the SuM. Referred here as inhibitory hippocampal-hypothalamic (IHH) cells, IHHs are believed to be localized to the hippocampal dentate gyrus (DG). IHH fibers have been identified near SuM-DG projecting neurons, a neuronal population which signals spatial novelty. Hence, this largely uncharacterized hippocampal cell population shows promise in modulating spatial novelty signals originating from the SuM (SuM-DG cells). We specifically hypothesized that IHH activation may suppress spatial novelty signals from the SuM and thereby impair discrimination of novelty and familiarity in a hippocampal-dependent task. To further investigate such claims, in-vivo optogenetic stimulation of IHH terminals (DG-SuM) was conducted during two behavioral assays: the hippocampal-dependent Object Location Memory (OLM) and the hippocampal-independent Object Recognition Memory (ORM) assessment. Opsin-positive and negative animals were prepared with ChR2 expression or a control virus expressing EGFP, respectively, localized to the hippocampal DG. Both groups completed the respective OLM and ORM assessments with a one-week break separating each behavior assessment. MATLAB was used to demarcate the time of investigation each animal spent per object, and a discrimination index was used to identify the investigatory preference of an animal. Following completion of the behavioral assessments, animals were euthanized to investigate implant location, virus expression and location, and tissue damage. Future experiments will continue to further characterize and investigate IHH’s connections and modulation over spatial-novelty signals originating from the supramammillary area.