Work

Acute ethanol enhances septohippocampal coordination but disrupts intrinsic hippocampal theta dynamics during foraging

Year: 2025

Type: article

Abstract: Theta oscillations – rhythmic patterns of synchronous activity within discrete brain regions – are known to support memory, navigation, and behavioral coordination, and are sensitive to pharmacological manipulation. Acute ethanol (EtOH) exposure has been shown to alter theta oscillations, but its effects on transient theta bursts and cross-regional coordination during naturalistic behavior remain unclear. We recorded local field potentials (LFPs) from the medial septum (MS), hippocampal Cornu Ammonis 1 (CA1), and medial prefrontal cortex (mPFC) in freely foraging mice following intraperitoneal injection of EtOH (1.5 g/kg) or saline. We analyzed spectral power, theta burst dynamics, phase, and lag timing. Burst features from CA1 were used to train a machine learning classifier to predict session condition. EtOH impaired locomotion and reduced goal-directed behaviors, particularly early in the session. In CA1, theta power shifted toward lower frequencies and lagged coherence declined. EtOH increased the frequency but reduced the duration of theta bursts in CA1, and in MS, only burst count increased. EtOH enhanced the temporal alignment of MS–CA1 burst pairs. Phase-locking between CA1 and MS during coupled bursts remained present but showed altered structure. Our classifier achieved robust performance using burst features such as skew and entropy, and reliably distinguished treatment conditions. EtOH modulates septohippocampal dynamics by altering the timing and structure of theta bursts. These results suggest that burst-level features are sensitive markers of EtOH’s circuit-level effects during naturalistic behavior. • Acute alcohol (ethanol) exposure disrupts hippocampal theta rhythmicity, reducing CA1 lagged coherence and shifting theta power toward lower frequencies, while sparing medial prefrontal cortex oscillations. • Local field potential recordings revealed that hippocampal and septal theta activity occurs as discrete bursts; ethanol increased burst counts but shortened CA1 burst duration. • Alcohol enhanced septohippocampal coordination by tightening temporal alignment of medial septum–CA1 burst pairs, even as overall hippocampal rhythmic stability was impaired. • Hippocampal theta bursts predicted locomotor initiation and movement vigor, but ethanol blunted post-burst increases in velocity, altering brain–behavior coupling. • Machine learning classification of theta burst features reliably distinguished alcohol from saline conditions, establishing burst-level metrics as sensitive biomarkers of ethanol’s circuit-level effects.

Source: Alcohol

DOI: 10.1016/j.alcohol.2025.11.001

Authors: Caleb B. Darden, Meagan D. Marks, Andrew J. Kesner

Institutions: National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, Indiana University Indianapolis, Indiana University – Purdue University Indianapolis

Language: English

Topic: Neural dynamics and brain function

Subfield: Cognitive Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,720