[R01] GABAergic Cells in the Periaqueductal Gray Region Control Food-Seeking
Ente: National Institute of Diabetes and Digestive and Kidney Diseases
Scadenza: 2028-03-31
Importo max: 546.971 EUR
Paese: US
Descrizione
Project Summary/Abstract
Abnormalities in feeding behaviors are a key symptom of several conditions, including binge-eating disorder,
anorexia and obesity. In order to develop novel treatments, it is imperative to gain a deeper understanding of the
circuits controlling adaptive feeding. Eating is affected by metabolic and hedonic features, and it consists of
several actions, including exploratory food-seeking and consumption. Despite its central clinical and biological
importance, networks controlling these behaviors are not well-understood. Prior data have indicated that
activation of several GABAergic inputs to the midbrain lateral and ventrolateral periaqueductal gray (l/vlPAG)
elicit hunting of insects in mice. However, the role of local l/vlPAG GABAergic cells in feeding is unknown.
Intriguingly, our preliminary data show that these cells encode food-seeking actions, such as approach to food
and consumption. Furthermore, activity in these ensembles, or of their projections to the subthalamic zona
incerta (ZI) are required for foraging leading to consumption of both prey and non-prey food. Here, we propose
to combine converging advances in neural activity recording, computational methods and molecular circuit
dissection tools to: 1. Characterize how l/vlPAG VGAT cells encode food sources and food-seeking behaviors
by recording the neural activity of large ensembles of cells with miniaturized microscopes. 2. Determine if activity
in the l/vlPAG circuit and their projection to the ZI is necessary and sufficient to promote foraging leading to
consumption, and 3. Dissect how the l/vlPAG input affects the ZI by combining ex vivo and in vivo recordings of
neural activity. Since prior reports show ZI activation induces feeding, we hypothesize that activation of the
inhibitory l/vlPAG input to ZI elicits feeding by disinhibiting the ZI. Importantly, feasibility for all proposed aims is
demonstrated in preliminary data and our prior publications, and we have successfully collaborated with all
participating key personnel. Taken together, execution of these aims will establish the function of a novel bottom-
up midbrain-subthalamic pathway that is vital for food-seeking actions, having direct implications for
understanding feeding mechanisms.
Istituzione: UNIVERSITY OF CALIFORNIA LOS ANGELES
PI: Avishek Adhikari
Progetto: 5R01DK139605-03
Settori: National Institute of Diabetes and Digestive and Kidney Diseases
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