Probing brain network dynamics in freely behaving animals

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Over the past decade, neuroscience has seen an explosion of new techniques that leverage light-based tools to visualize and manipulate brain activity. Combined with powerful genetic methods that allow for targeted expression of light-based protein actuators or light-emitting activity reporters, the field now has the ability for a formerly unthinkable level of precision and insight into the working brain in freely behaving animals. We, and others at the University of Calgary have leveraged these approaches to gain new knowledge about social behavior, defensive responses to threat or control of brain blood flow. These insights have required the parallel development of data analysis pipelines, computational tools and machine learning approaches. This is global effort, but significant inroads are being made by researchers in Calgary. Currently, we have the capacity to either: 1) record activity of cell populations in the brain using genetically expressed calcium indicators, such as GCaMP, that allow for the observation of calcium fluctuations in genetically identified cell populations, or: 2) manipulate activity, (discrete activation or inhibition of defined cell populations) using optogenetic approaches. Neural activity is recorded using miniature microscopes that allow for real-time activity readouts in a freely behaving animal at the resolution of a single sell. Activity is manipulated using implanted optical fibres that allow for the delivery of light at specific wavelengths to activate or inhibit cells. These parallel information streams offer important information but we cannot observe and manipulate cell activity in the same experiment, which means that linking the two approaches is inferential. Here we request funding for two nVoke miniature microscopy systems that combine simultaneous activity sampling with manipulation in a single head-mounted unit. These will upgrade existing Inscopix miniature microscopes that have imaging only capabilities. As one example, we will use this equipment to record and perturb PVNCRH activity during social and defensive behaviors and allow us to determine whether discrete projections from specific PVNCRH neurons to one brain target mediate one behavior (social approach) vs another (defensive escape). This will provide new information that begins to advance and test ideas related to functional heterogeneity in PVNCRH populations and lead to more targeted manipulations of defensive, social and stress behaviors. The upgraded equipment will be housed in the CSM Optogenetics Core Facility where it will be under the oversight of trained staff scientists. This will also allow other research groups to access this equipment for other explorations linking brain circuits and behavior.