# C4-Effects on Corticothalamic function

> **NIH NIH P50** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2024 · $213,027

## Abstract

Impairments in executive function are among the most devastating consequences of prenatal alcohol exposure
(PAE), for which there are few effective treatments. Our long-term goal is to identify key neural mechanisms
underlying these impairments, to facilitate the development of circuit-specific treatments for Fetal Alcohol
Spectrum Disorders (FASDs). Our objective is to leverage in vivo behavioral electrophysiology to determine
the impact of PAE on corticothalamic functional coupling, and its relationship to visuospatial working memory,
rule learning/switching, myelination and CircRNA/Neuroimmune signaling. Our central hypothesis is that PAE
induces alterations in the functional connectivity of reciprocal circuits connecting the mediodorsal thalamic
nuclei and the medial prefrontal cortex (MD↔mPFC), which underlie deficits in working memory and cognitive
flexibility in FASD, and which are mediated by decreased MD↔mPFC myelination and associated with
transcriptional blood biomarkers. Our rationale for the use of in vivo behavioral electrophysiology during the
resting-state as well as during visuospatial rule learning/switching is to provide a comprehensive view of the
effects of PAE on functional MD↔mPFC connectivity and its impact on behavior. In Aim 1, we will use dual site
high-density silicon electrode recordings in freely behaving mice in the home cage to detect and characterize
resting state functional connectivity to test the hypothesis that developmental ethanol exposure reduces
resting-state neural oscillations associated with cognitive abilities, increases resting-state spiking activity within
MD/mPFC microcircuits, and decreases resting-state MD↔mPFC spike-field coherence. In Aim 2, we will
determine the effects of PAE on MD↔mPFC function during visuospatial learning/performance and a rule
switch to test the hypothesis that PAE disrupts visuospatial working memory and cognitive flexibility within
local MD/mPFC microcircuits. We will also use spike/field coherence and phase/amplitude coupling to test the
hypothesis that PAE reduces the functional integration of MD-encoded task-relevant information to the mPFC,
and vice versa. In Aim 3, we will determine the effects of PAE on the relationship between resting state
MD↔mPFC electrophysiology, and visuospatial learning/flexibility, task-based neuronal tuning, white matter
integrity, and circRNA/neuroimmune status. These comparisons will collectively test the hypothesis that
resting state corticothalamic function predicts (or is predicted by) behavioral performance, neuronal tuning to
cues/delays/behavior, and white matter integrity and circRNA/neuroimmune status. The research proposed in
this application is innovative because it will systematically characterize, for the first time, the developmental
effects of ethanol on interactions among key components of the cognitive thalamus essential in executive
functioning. The proposed research is significant because it will elucidate novel function...

## Key facts

- **NIH application ID:** 10741690
- **Project number:** 2P50AA022534-11
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** David Nathaniel Linsenbardt
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $213,027
- **Award type:** 2
- **Project period:** 2014-08-05 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10741690

## Citation

> US National Institutes of Health, RePORTER application 10741690, C4-Effects on Corticothalamic function (2P50AA022534-11). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10741690. Licensed CC0.

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