Opto-electrical bimodal recording of neural activity in awake head-restrained mice

Electrical and optical monitoring of neural activity is major approaches for studying brain functions. Each has its own set of advantages and disadvantages, such as the ability to determine cell types and temporal resolution. Although opto-electrical bimodal recording is beneficial by enabling us to exploit the strength of both approaches, it has not been widely used. In this study, we devised three methods of bimodal recording from a deep brain structure in awake head-fixed mice by chronically implanting a gradient-index (GRIN) lens and electrodes. First, we attached four stainless steel electrodes to the side of a GRIN lens and implanted them in a mouse expressing GCaMP6f in astrocytes. We simultaneously recorded local field potential (LFP) and GCaMP6f signal in astrocytes in the hippocampal CA1 area. Second, implanting a silicon probe electrode mounted on a custom-made microdrive within the focal volume of a GRIN lens, we performed bimodal recording in the CA1 area. We monitored LFP and fluorescent changes of GCaMP6s-expressing neurons in the CA1. Third, we designed a 3D-printed scaffold to serve as a microdrive for a silicon probe and a holder for a GRIN lens. This scaffold simplifies the implantation process and makes it easier to place the lens and probe accurately. Using this method, we recorded single unit activity and LFP electrically and GCaMP6f signals of single neurons optically. Thus, we show that these opto-electrical bimodal recording methods using a GRIN lens and electrodes are viable approaches in awake head-fixed mice.