Abstract

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.

Highlights

  • Electrical and optical monitoring of neural activity is major approaches for studying brain functions

  • Electrical recording has the advantage of high temporal resolution, which allows us to detect action potentials of individual neurons and high frequency neural oscillations reflecting the functional state of a local n­ etwork[2,3,4,5,6,7]

  • We show three methods of bimodal recording, in each of which we combined optical imaging through a GRIN lens and a custom-made microscope (Fig. 2) with different ways to record electrical activity

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Summary

Introduction

Electrical and optical monitoring of neural activity is major approaches for studying brain functions. One can monitor different functional states of the brain using electrical recording of local field potential (LFP) and simultaneously characterize the activity of a large number of a specific cell type using calcium ­imaging[10,11]. Another example would be to characterize the relationship between neuronal activity, which can be monitored electrically, and the activity of astrocytes, which requires calcium imaging. By chronically implanting the GRIN lens and electrodes in proximity, our method allows for simultaneous opto-electrical monitoring from the same brain area in awake head-fixed mice (Fig. 1) In such bimodal recording, one main challenge is the precise placement of the lens and electrode. We present three examples of opto-electrical bimodal recording to provide the ideas of how these methods can be implemented in different lines of studies

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