Creating an integrated platform for in vivo brain targeting and experimentation

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The central nervous system (CNS) controls myriad physiologic processes, from storing memories to controlling muscle movement and regulating appetite. To understand the roles of discrete neural populations in vivo, modern neuroscience has developed viral-based tools to control neuron activity with light (optogenetics) and to quantify real-time changes in neuronal activity by monitoring fluorescence of intracellular calcium reporters (photometry). These two tools are critical components of a neuroscientist's toolkit to decipher the precise neural circuits that underlie animal behavior, but require dedicated complex instrumentation. Additionally, the use of optogenetics and fiber photometry is predicated on the ability to deliver viral vectors with high spatial precision and reproducibility within micrometres to discrete CNS neuronal populations to express the light-gated ion channels or the calcium reporters. To facilitate these viral injections, intracranial surgeries using a stereotaxic frame are essential, allowing micrometre precision of movement in 3-dimensional space of a manipulator arm for viral delivery to the brain. Together, these three technologies (high precision targeting, photometry, and optogenetics) a broad range of neuroscience research avenues; allowing us to track and control neurons contained in defined CNS sites and perform functional studies to understand their function in the living animal. This proposal seeks to create an integrated platform for in vivo brain targeting and experimentation. We request funding to purchase two high-precision stereotaxic frames with microinjectors, optogenetic equipment for neuroactivation and photometry equipment for in vivo calcium imaging. Critically, this equipment will alleviate severe bottlenecks in our current experimental set-up and provide a major technological improvement over our current hardware. Importantly, this instrumentation will empower seven NSERC-supported research groups to pursue impactful neuroscience research at the Research Institute of the McGill University Health Centre (RIMUHC) (Sabatini, Huang, Suvrathan, Stellwagen, Sjöström, Chen, and Murai) and greatly benefit the broader neuroscience community at McGill University in implementing innovative techniques and approaches. This equipment will be used to train more than 50 HQP over the coming 5 years and this expertise will greatly benefit them as they pursue careers in diverse fields of science, medicine, and industry. We will specifically utilize this equipment in training and workshops for students coming from underrepresented groups and developing countries, which our group regularly hosts annually. As our team does not have access to this equipment through other means, the successful funding of this proposal will rapidly enhance the impact of our NSERC-funded research and allow critical access to and training with powerful technology to understand the neural circuits underlying behavior.