FIP IN-PERSON Seminar for Postdoc Speaker Award "Light-sheet imaging of large-scale neural population activity in the retina"
We have developed a single-photon light-sheet imaging system that allows us to measure activity of hundreds of retinal neurons at specific laminar depths, while simultaneously driving their activity though patterned visual stimulation (Fig. 1a). We have validated the performance of our system by imaging retinas from mice expressing GCaMP6f in subpopulations of BCs and RGCs (Fig. 1c, d). We measured calcium fluorescence in hundreds of RGCs across a field of view extending ~1.5mm each dimension, under spontaneous and visual stimulus driven conditions, at single cell resolution for extended periods of time. A semi-automated algorithm was used for extracting the responses of RGCs to different stimuli such as moving bars, checkerboard noise and contrast and luminance modulation, and then classifying RGCs into distinct functional types. We were also able to extract spatiotemporally precise calcium responses in dendrites, especially dendritic spines of individual RGCs. Finally, we were able to measure fluorescence changes caused by influx of calcium in the synaptic terminals of different BCs that contact RGCs and characterize the fluorescence responses based on their spatiotemporal correlations. Thus, this platform enables characterization of neural circuit functions of distinct populations of neurons in specific layers of the retina. Our next step is to combine this technology with a multi-electrode array, to achieve a high-throughput characterization of neural circuit computations in synaptically coupled BC-RGC circuits and their impact on the retinal output.