BRAIN project (Histed): Readout and Control of Spatiotemporal Neuronal Codes of Behavior

National Institute Of Mental Health

Investigators

Linked publications, trials & patents

Abstract

In this project period, we have developed means of stimulating single neurons in the cortex. We have deployed a dual-laser custom microscope capable of imaging and stimulation. To make cortical neurons accessible for imaging activity and stimulation, we have developed an approach to express soma-targeted ChrimsonR (stChrimsonR) combined with expression of GCaMP variants. This allows high efficiency all-optical stimulation at 1030 nm (laser repetition rate: 500 kHz) and imaging at 920 nm (laser repetition rate: 80 MHz). To assess the effect of stimulating spatial and temporal patterns, we have done preliminary work to show which V1 spikes generated by a visual stimulus are used by the animal in detection behavior. We have measured the effect of inhibiting V1 at different times relative to stimulus onset. Resulaj et al. (2018 eLife) previously reported that only early spikes of V1 (in the first 40-80 ms of V1 neurons stimulus response) were used for visual discrimination, but they observed no effect on visual detection. We used a near-threshold change detection task, in VGAT-ChR2 animals that detected a contrast increment of a visual grating. One-photon optical stimulation was delivered to the surface of visual cortex. We found the same effect holds for visual detection: only the early spikes of V1 responses (within the first 80ms) are used. We have also demonstrated that secondary visual areas play a role in very simple visuomotor behaviors in which all information should be available in primary visual cortex. This work sheds light on the network of cortical brain areas that control perceptual behavior for example, does information flow directly from primary visual cortex to frontal or motor areas, or does it pass through secondary areas? Primary visual cortex (V1) projects to numerous brain areas, including several secondary visual areas, frontal cortex, and basal ganglia. While it has been demonstrated that optogenetic silencing of V1 strongly impairs visually-guided behavior, it is not known which downstream areas are required for visual behaviors. Optogenetic silencing of visual responses in secondary visual areas revealed that their activity is required for even this simple visual task. In vivo electrophysiology showed that, although inhibiting secondary visual areas could produce some feedback effects in V1, the principal effect was profound suppression at the location of the optogenetic light. The results show that pathways through secondary visual areas are necessary for even simple visual behaviors. We have developed and refined a robust protocol to co-express stChrimsonR and GCaMP8s in the same cortical neurons in vivo and have shared this protocol with the consortium.