# Dynamic GABAergic control of energy balance-regulating neurons in the VMH

> **NIH NIH R21** · TUFTS UNIVERSITY BOSTON · 2022 · $442,050

## Abstract

Project Summary
Energy balance and body weight control result from coordinated appetitive and physiological responses to
nutrient and hormonal signals informing the caloric status of the animal. Complex hypothalamic neural networks
are critical in organizing these responses. Our previous studies identified an essential role for brain-derived
neurotrophic factor (BDNF) in central neural circuits regulating food intake and body weight. BDNF is a major
regulator of synaptic transmission and plasticity in the mature brain and is synthesized and released by excitatory
neurons in an activity-dependent manner. Among known energy balance centers, it is most abundant in the
ventromedial hypothalamus (VMH), where it plays a required satiety role in the adult animal. Accordingly, its
expression and that of its receptor TrkB, is elevated there in the fed state and depletion of BDNF in this region
results in over-eating and excessive weight gain in mice. Neurons in the VMH are predominantly glutamatergic
and mediate food intake suppression when activated. It is now recognized that feeding circuits are not hardwired
but highly plastic and remodel in response to caloric signals to meet the energy demands of the animal. This
form of synaptic plasticity has been well studied in the arcuate nucleus of the hypothalamus but not in the VMH.
This exploratory project will investigate whether dynamic changes in GABAergic transmission occur in response
to energy cues in the VMH to mediate energy balance control. Although GABAergic neurons are largely absent
in the VMH, inhibitory GABAergic fibers originating elsewhere and GABAA receptors are abundant in this region.
We will test the hypothesis that increased phasic (synaptic) GABAergic inhibition in the fed state provides
feedback control of anorexigenic BDNF+ cells in the VMH to prevent neuronal over excitation and extended
anorexia. Furthermore, we will determine whether tonic (extrasynaptic) GABAergic currents negatively regulate
these cells in the fasted state to restore energy stores. In total, these investigations will inform how homeostatic
changes in synaptic and extrasynaptic GABAergic transmission regulate VMH BDNF+ neurons to promote
energy balance and metabolic health.

## Key facts

- **NIH application ID:** 10536368
- **Project number:** 1R21NS125697-01A1
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **Principal Investigator:** Maribel Rios
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $442,050
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10536368

## Citation

> US National Institutes of Health, RePORTER application 10536368, Dynamic GABAergic control of energy balance-regulating neurons in the VMH (1R21NS125697-01A1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10536368. Licensed CC0.

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