FIP Seminar: Development and application of a calcium sensor for recording neuronal activity in freely-moving mice at cellular resolution

Recording large-scale brain activity patterns at cellular resolution in freely-behaving mice using current recording approaches presents several challenges. First, linear microscopy methods lack the depth penetration and optical sectioning required for deep-tissue recording, while multiphoton microscopy allows for recording neuronal activity only from a single plane or few axially-shifted planes. In addition, cellular-resolution recording requires a mouse to either be head-fixed under a microscope or to have a miniaturized imaging device attached onto its skull. Both can impact mouse behavior and underlying brain activity. Recently, my lab showed that utilizing an integrator for calcium-dependent recording of neuronal activity (CaMPARI) allows for cellular-resolution imaging of large-scale brain activity patterns in freely-behaving mice without needing to attach any mechanical device. It was also shown that despite the enhanced in vitro performance of the second generation of CaMPARI (CaMPARI2), it exhibits poorer in vivo neuronal activity recording sensitivity when compared to CaMPARI1 in mice. Here, we present an ongoing work to develop a new generation of the CaMPARI sensor (CaMPARI3), which will overcome the limitations of the previous generations. We developed an in vitro-in vivo screening pipeline and found that the photoconversion properties of the same sensors in vitro and in vivo do not correlate. Rather, the peak DF/F in vitro may better predict the rate of photoconversion in vivo. We present our progress with developing CaMPARI3, which exhibits enhanced photoconversion and also the ability for recording dynamic changes in neuronal activity. Therefore, CaMPARI3 is expected to expand the possible experimental applications to record single-cell resolution brain activity from freely-behaving mice.
Hod Dana received his B.Sc. (summa cum laude) and Ph.D. degrees in Biomedical Engineering from the Technion - Israel Institute of Technology. During his PhD work he developed advance nonlinear microscopy methods for recording of large-scale neuronal activity. Dr. Dana did his post-doctoral training with the GENIE project at the Howard Hughes Medical Institute Janelia Research Campus. As a postdoctoral researcher, he was involved in the development and testing of new calcium sensors for recording neuronal activity.