Bradford Lowell, MD, PhD

Institution: Beth Israel Deaconess Medical Center
Research: Neural control of hunger, energy balance, metabolism and autonomic function
Grants & Publications: Harvard Catalyst
Categories: BIDMC

We utilize genetic engineering techniques in mice, electrophysiology, optogenetics, chemogenetics, rabies mapping, ChR2-assisted circuit mapping, in vivo assessments of neuronal activity, and single neuron transcriptomics to elucidate neural circuits controlling hunger and energy balance, neuroendocrine regulation and autonomic function. Neuron-specific recombinase driver mice are used in conjunction with recombinase-dependent AAVs expressing various genetically encoded “tools” to selectively (in a neuron cell type-specific fashion): a) map connectivity between neurons to establish their “wiring diagrams”, b) manipulate neuron firing rates in vivo to determine their roles in regulating behavior and physiology, and c) measure neuron activity in vivo to establish their responses to discrete behavioral and physiologic perturbations. These three parameters are key to understanding how neurons and their circuits control of behavior and physiology.

The above-mentioned approaches are powerful. However, their impact is sometimes limited by the fact that we do not know the different neurons that make up each “homeostatic” brain region (i.e., the “parts list”), and related to that, we do not have the “enabling” recombinase mice that would provide experimental access to these important, but presently unknown, neurons. We are addressing this by: 1) performing single-neuron transcriptomics on “homeostatic” brain regions to reveal: i) the different neurons that exist in each of these brain sites (i.e., the “parts list”), and ii) the genetic markers that specify each of the unique “parts” (i.e., the neurons). 2) We then use these genetic markers and CRISPR genetic engineering to rapidly generate mice expressing recombinases in each of the interesting, novel neurons. 3) Finally, we use these mice to uncover the wiring diagrams and determine the role these novel neurons play in regulating energy homeostasis and autonomic function.

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