# Ethanol and brain state-dependent neural signaling

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2021 · $339,818

## Abstract

Alcohol consumption impairs motor coordination, attentional efforts and memory function. Alcohol-impaired
driving accounted in 2013 for ~31% of all traffic accidents resulting in 10,076 fatalities and $59 billion crash-related cost. We propose to study the mechanisms how ethanol affects brain state-dependent neural
signaling. Brain state-dependent signaling comprises adjustments in cellular and circuit activity to optimize
how the brain processes information in a distinct behavioral context. We and others have used a locomotion
paradigm to reveal that noradrenergic signaling is involved when such optimizations occur. At transitions
from rest to locomotion astroglia, the support cells in the central nervous system, are norepinephrine-dependently activated simultaneously in brain regions as disparate as the cerebellum and primary visual
cortex. The noradrenergic system is involved to support attentional efforts and in gating synaptic plasticity. It
has long been known that alcohol can suppress the activity of locus coeruleus, the structure where
noradrenergic neurons are clustered; however, it is still unclear what the consequences are for the activity of
individual brain cells during active behavior. We propose to test the hypothesis that alcohol severely impairs
brain state-dependent noradrenergic neuromodulation in an astroglia-dependent manner. Our approach is to
combine specific mouse lines for cell type-selective genetic manipulation and expression of Ca2+ sensors with
our motorized linear treadmill and two-photon microscopy to study Ca2+ dynamics and electrical activity in
well-controlled behavioral states. These in vivo investigations will be complemented with acute slice Ca2+
imaging and electrophysiology experiments. We will focus our investigations on the cerebellum for its
relatively straightforward circuit arrangement that facilitates mechanistic studies. The novel utilization of a
specific Cre mouse line will enable us to selectively manipulate Bergmann glia, the astrocytes of the
cerebellar molecular layer, but not astrocytes of the granule cell layer. We will pursue the following aims: (1)
We will define extent and mechanism of the effect of acute ethanol on locomotion-induced Bergmann glia
Ca2+ activation. (2) We will reveal ethanol-sensitive components of locomotion-induced Purkinje cell Ca2+
dynamics and dissect the relationship to Bergmann glia function. (3) We will investigate how locomotion-
induced Purkinje cell Ca2+ dynamics regulate intrinsic and synaptic activity. Upon conclusion of our proposed
studies we will have learned what components of brain state-dependent noradrenergic neural signaling are
impaired by ethanol. This work will reveal how ethanol might exert its detrimental effects on attentional
efforts and memory on the cellular and circuit level. These studies will further build the groundwork for future
research on brain state-dependent neural signaling under neurodegenerative and neurobehavioral conditions
assoc...

## Key facts

- **NIH application ID:** 10190737
- **Project number:** 5R01AA025128-05
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Martin Paukert
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $339,818
- **Award type:** 5
- **Project period:** 2017-09-05 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10190737

## Citation

> US National Institutes of Health, RePORTER application 10190737, Ethanol and brain state-dependent neural signaling (5R01AA025128-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10190737. Licensed CC0.

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