UC San Diego

Within the hippocampus, a subclass of interneurons known as parvalbumin positive (PV+) interneurons, play an important role in generating neural oscillations and in influencing the firing rate of pyramidal cells. To maintain such an extensive control, PV+ interneurons have a high energy demand, but how PV+ interneurons are able to generate enough energy is not well understood. Previous studies have shown that dysregulation in mitochondrial subunits, Cox6a1 and Cox6a2, has impaired the activity of complex IV within mitochondria. In this study, we investigate Cox6a1 and Cox6a2 to understand their contribution to mitochondrial function in PV+ interneurons and whether they are necessary for PV+ interneurons to maintain function. Through an AAV-miR construct, we were able to successfully reduce levels of Cox6a1 and Cox6a2 within PV+ interneurons selectively in the CA1 region of the mouse hippocampus. Electrophysiological recordings from that region revealed that reducing Cox6a1 did not have an effect on the firing rate of interneurons and pyramidal cells or on neural oscillations generated in CA1 but did increase the number and size of place fields. Reducing Cox6a2 decreased the firing rate of pyramidal cells, decreased the frequency of theta and gamma oscillations, and also increased the number and size of place fields. Because reducing levels of Cox6a2 in PV+ interneurons disrupted neuronal oscillations and neuronal firing patterns in the hippocampus, this suggests that hippocampus-dependent memory function relies on a specialized regulation of mitochondrial activity in PV+ interneurons.