# Enduring effects in thalamocortical circuits ensuing perinatal opioid exposure

> **NIH NIH F31** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $31,937

## Abstract

Project Summary/Abstract
Illicit use of synthetic opioids, primarily fentanyl, has increased dramatically since the 1990s, leading to what is
now recognized as the opioid epidemic. Fentanyl is fifty times more potent than heroin and is now responsible
for many opioid-related overdose deaths. Fentanyl use among pregnant women has increased dramatically in
the past decade, which severely undermines their child’s neurological development. Longitudinal clinical
studies reveal an increased incidence of sensory-related deficits in adolescents who were exposed to opioids
prenatally. The thalamus and neocortex are essential for normal sensory function, and share reciprocal
connections, forming the thalamocortical (TC) and corticothalamic (CT) circuit. It is possible that the effects
fentanyl exerts in this circuit could lead to long-lasting sensory-related deficits. Consistent with this, our data
indicate that perinatal fentanyl exposure upregulates the expression of metabotropic glutamate receptor 4
(mGluR4), which is a group III mGluR that suppresses neurotransmitter release. My data suggest that perinatal
fentanyl exposure suppresses synaptic inputs to ventroposteromedial (VPM) thalamic and primary
somatosensory (S1) cortical neurons in adolescent mice. Consistent with the critical role of these projections in
sensory processing, these mice have an impaired ability to adapt to tactile stimulation. I hypothesize that
perinatal fentanyl exposure leads to a lasting suppression of synaptic activity by increasing mGluR4
expression in thalamocortical and corticothalamic circuits, resulting in sensory abnormalities.
I will test predictions that corroborate this hypothesis with three specific aims. First, I will determine whether
perinatal fentanyl exposure suppresses synaptic transmission in TC-CT. Then, I will determine whether this
exposure increases functional expression of mGluR4 in this circuit. Finally, I will determine whether this
exposure impairs sensory network activity both ex vivo and in vivo. These specific aims and experiments will
allow the elucidation of the mechanisms that will explain, in part, the underlying pathophysiology of sensory-
related conditions associated with perinatal exposure to fentanyl and will contribute to improving treatment and
prevention strategies.
I have completed all required coursework in the Program of Neuroscience at the University of Maryland School
of Medicine and have passed my qualifying exam. This allows me to devote much of my time to the completion
of my proposed experiments under the guidance of my Sponsor, Dr. Asaf Keller, a leading expert in sensory
perception and the effects of drugs of abuse on the developing brain. I am also mentored by Dr. Yavin Shaham
(NIDA), an expert on the neurodevelopmental impact of drugs of abuse, including opioids, and Dr. Margaret
McCarthy (UMSOM), a leading expert on rodent brain development. All together, these planned experiments
and the guidance from my research team wil...

## Key facts

- **NIH application ID:** 10136895
- **Project number:** 1F31DA051113-01A1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Jason Bondoc Alipio
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $31,937
- **Award type:** 1
- **Project period:** 2021-04-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136895

## Citation

> US National Institutes of Health, RePORTER application 10136895, Enduring effects in thalamocortical circuits ensuing perinatal opioid exposure (1F31DA051113-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10136895. Licensed CC0.

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