# Functional anatomy, physiology and behavioral responses mediated by mu opioid receptor signaling on medial thalamic neurons.

> **NIH DA R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2026 · $595,171

## Abstract

Project Summary/ Abstract
Opioids like morphine are the most effective pain relieving drugs available but their rewarding properties lead
to misuse. The rewarding and analgesic properties of opioids are mediated by activation of mu opioid receptors
(MOR). Hyperalgesia is an exaggerated pain perception in response to a stimulus that is normally mildly
uncomfortable. Hyperalgesia occurs when opioid-dependent people discontinue opioid use, known as opioid
withdrawal-induced hyperalgesia (OWIH). Opioids also relieve this hyperalgesia providing motivation for
continued opioid use and dose escalation. Midline thalamic (MThal) nuclei are key hubs responsible for
activating brain regions involved in opioid modulation of pain and motivation. However, we lack critical details
about what aspects of opioid-mediated behavior and physiology are due to MOR activation on thalamic
neurons. We have found that glutamate transmission from MThal neurons to cortical and striatal brain regions
is inhibited by MOR agonists like morphine. We hypothesize that MThal neurons are a heterogeneous mix of
MOR-expressing and MOR-lacking neurons. We further hypothesize that prolonged inhibition of MThal
neurons by opioids can induce adaptations leading to hyperalgesia upon opioid withdrawal (OWIH) while acute
opioid-inhibition of MThal neurons will attenuate hyperalgesia. The long term goal of this project is to
understand what neurons in the MThal express MOR, how these MOR-expressing MThal neurons respond to
conditions that cause hyperalgesia, including OWIH, and whether inhibition of these neurons is sufficient to
suppress hyperalgesia. We will use behavioral pharmacology, imaging, whole-cell electrophysiology, and
optogenetic manipulations in mice to gain a foundational understanding of how opioid action in thalamo-
cortico-striatal brain circuits ultimately affect hyperalgesia and antihyperalgesia.
Aim 1 will determine the relative abundance of both MOR-expressing and MOR-lacking medial thalami

## Key facts

- **NIH application ID:** 11294482
- **Project number:** 1R01DA062636-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** William T Birdsong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** DA
- **Fiscal year:** 2026
- **Award amount:** $595,171
- **Award type:** 1
- **Project period:** 2026-05-01T00:00:00 → 2031-02-28T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11294482

## Citation

> US National Institutes of Health, RePORTER application 11294482, Functional anatomy, physiology and behavioral responses mediated by mu opioid receptor signaling on medial thalamic neurons. (1R01DA062636-01A1). Retrieved via AI Analytics 2026-07-12 from https://api.ai-analytics.org/grant/nih/11294482. Licensed CC0.

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