# Alcohol and Developing Neuronal Circuits

> **NIH NIH R01** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2024 · $521,566

## Abstract

Project Summary / Abstract
Cognitive function deficits are among the most devastating consequences of fetal alcohol exposure.
Currently available treatments against these deficits have limited efficacy. Our long-term goal is to
identify specific functional mechanisms underlying the cognitive deficits associated with FASDs, so
that circuit-specific treatments can be developed to prevent and correct them. Our objective is to
leverage both in vitro and in vivo electrophysiological approaches to determine the long-term impact
of third trimester-equivalent ethanol exposure (TTAE) on the limbic memory system. Our central
hypothesis is that TTAE disrupts the balance of excitatory and inhibitory synaptic transmission at
hippocampal formation→retrosplenial cortex (RSC) and RSC↔anterior thalamic nucleus (ATN)
synapses, leading to deficits in information flow within and between these brain regions. Our rationale
for the use of complementary in vitro and in vivo electrophysiological approaches is to provide a multi-
scale view of the effects of TTAE on functional hippocampal CA1, subiculum (SUB), RSC and ATN
connectivity. In Aim 1, we will determine the effects of TTAE on the function of CA1→RSC and
SUB→RSC pathways. We will use slice electrophysiology, retrograde labeling, and optogenetics to
test the hypothesis that TTAE persistently reduces glutamatergic transmission at SUB→RSC
synapses, and increases direct monosynaptic long-range inhibition (CA1→RSC) and indirect
feedforward di-synaptic inhibition (SUB→RSC interneurons→RSC pyramidal neurons). We will also
use high-density silicone electrode recordings in freely behaving mice to test the hypothesis that
ethanol exposure reduces the number, efficiency, and information content of high frequency
oscillatory bursts in the RSC that are important for memory. In Aim 2, we will determine the effects of
TTAE on the function of ATN↔RSC pathways. We will test the hypothesis that TTAE persistently
reduces glutamatergic transmission at reciprocal monosynaptic connections between the ATN and
RSC, without affecting di-synaptic feedforward inhibition at RSC→thalamic reticular nuclei→ATN
synapses. We will also test the hypothesis that TTAE disrupts the activity of ATN and RSC neurons
specifically modulated by an animal’s head direction that are essential in spatial learning and
memory. 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 limbic memory network. The proposed research is significant because it will
elucidate novel functional neurobiological mechanisms underlying developmental ethanol exposure-
induced cognitive deficits, and identify specific biological targets for interventions to ameliorate them.

## Key facts

- **NIH application ID:** 10908484
- **Project number:** 5R01AA015614-18
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Carlos Fernando Valenzuela
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $521,566
- **Award type:** 5
- **Project period:** 2005-04-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10908484

## Citation

> US National Institutes of Health, RePORTER application 10908484, Alcohol and Developing Neuronal Circuits (5R01AA015614-18). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10908484. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*