How does the brain detect and respond to existing and anticipated disturbances in energy balance? To answer this, and other related questions, we utilize neuron-specific recombinase driver mice 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. Specific approaches utilized include, electrophysiology, optogenetics, chemogenetics, rabies mapping, ChR2-assisted circuit mapping, in vivo assessments of neuronal activity, and single neuron transcriptomics. Such efforts are discovering the neural circuits that generate “hunger”, and the mechanisms by which “hunger” guides behavior and physiology, and the ways in which the brain controls other related homeostatic drives, the autonomic nervous system and the neuroendocrine system. For more information on the above-mentioned topics and approaches see the following two reviews and chapter:
Lowell BB, Swanson LW and Horn JP. Chapter 41. The Hypothalamus: Autonomic, Hormonal, and Behavioral Control of Survival. In Principles of Neural Science (Eds. Kandel, Koester, Mack and Siegelbaum), 6th Edition, 2021.
Click here for all Brad Lowell’s publications on Pubmed
Current NIH Support:
NIH R01 DK075632 Lowell (PI) “The AgRP / POMC -> Paraventricular (PVH) -> Parabrachial (PBN) -> Limbic/Reward Satiety Circuit” Click here for description.
NIH R01 DK089044 Lowell (PI) “Leptin, GABAergic Neurons and Feedback / Feedforward Regulation of Energy Balance” Click here for description.
NIH R01 DK096010 Lowell (PI) “AgRP neurons: circadian control and interactions with the HPA axis” Click here for description.
NIH R01 DK134427 Lowell (PI) “Feedforward Activation of AgRP Neurons and Hunger”
NIH R01 DK122976 Multi-PI R01 Lowell (PI), Liberles (PI) “Leveraging the rich genetic diversity of vagal motor neurons to decode brain-to-gut communication” Click here for description.
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