# Midbrain astrocytes controlling active avoidance learning

> **NIH NIH R21** · UNIVERSITY OF TEXAS SAN ANTONIO · 2022 · $181,000

## Abstract

Learning to avoid aversive outcomes promotes resilience and suppresses the expression of generalized fear
in humans. As such, there is great interest in identifying the cellular processes that mediate active avoidance
learning. The first step in active avoidance learning is to actively respond during the aversive encounter, a
process that is controlled by ventral tegmental area (VTA) dopamine neurons. Recent research indicates
learning is not solely driven by neurons, but rather by astrocyte-neuron interactions. Therefore, one must
determine how VTA astrocytes regulate dopamine neurons during aversive situations to delineate the cellular
processes that control active avoidance learning.
 Astrocytes are active participants in local neural circuits as they respond to neurotransmitters and release
transmitters themselves. In particular, activation of Gq coupled receptors on astrocytes promotes the Ca2+-
dependent release of glutamate. Photometry recordings of astrocyte Ca2+ levels were performed to examine the
cellular activity of VTA astrocytes during aversive situations. Preliminary findings illustrate VTA astrocyte Ca2+
levels increased in rats trained on an inescapable footshock task. Furthermore, selectively stimulating Gq
signaling in VTA astrocytes reduced the latency to initiate actions during inescapable stress and elevated
dopamine levels in the nucleus accumbens (NAc). Together, these data highlight VTA astrocytes (1) undergo
changes in cellular activity during aversive situations, (2) regulate dopamine levels in the NAc and (3) promote
active behavioral responses during inescapable stress. Since active responding is a necessary first step for
active avoidance learning, VTA astrocytes are likely a central node for controlling avoidance learning. The
overarching hypothesis of this proposal is that VTA astrocytes facilitate active avoidance learning through the
Ca2+-dependent release of glutamate in the VTA and subsequent elevation of dopamine levels in the NAc. To
address this, the experiments in this proposal will virally manipulate VTA astrocyte Ca2+ signaling while
recording VTA astrocyte Ca2+ levels, neuronal glutamate signals in the VTA, and dopamine levels in the NAc.
Collectively, this proposal will delineate the role of VTA astrocytes during active avoidance learning.

## Key facts

- **NIH application ID:** 10419855
- **Project number:** 1R21MH127466-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS SAN ANTONIO
- **Principal Investigator:** Matthew J. Wanat
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $181,000
- **Award type:** 1
- **Project period:** 2022-05-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10419855

## Citation

> US National Institutes of Health, RePORTER application 10419855, Midbrain astrocytes controlling active avoidance learning (1R21MH127466-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10419855. Licensed CC0.

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