GRINtrode: A neural implant for simultaneous two-photon imaging and extracellular electrophysiology in freely moving animals

Significance In vivo imaging and electrophysiology are powerful tools to explore neuronal function that each offer unique complementary information with advantages and limitations. Capturing both data types from the same neural population in the freely moving animal would allow researchers to take advantage of the capabilities of both modalities and further understand how they relate to each other. Aim Here we present a head-mounted neural implant suitable for in vivo two-photon imaging of neuronal activity with simultaneous extracellular electrical recording in head-fixed or freely moving animals. Approach A GRIN lens-based head-mounted neural implant with extracellular electrical recording provided by tetrodes on the periphery of the GRIN lens was chronically implanted. The design of the neural implant allows for recording from head-fixed animals, as well as freely moving animals by coupling the imaging system to a coherent imaging fiber bundle. Results We demonstrate simultaneous two-photon imaging of GCaMP and extracellular electrophysiology of neural activity in awake head-fixed, and freely moving mice. Using the collected information, we perform correlation analysis to reveal positive correlation between optical and local field potential recordings. Conclusion Simultaneously recording neural activity using both optical and electrical methods provides complementary information from each modality. Designs that can provide such bimodal recording in freely moving animals allow for the investigation of neural activity underlying a broader range of behavioral paradigms.