Darden Caleb B, Marks Meagan D, Kesner Andrew J
National Institute on Alcohol Abuse and Alcoholism, Unit on motivation and Arousal, Division of Intramural Clinical and Biological Research, NIH, Bethesda, MD, USA.
Indiana University - Indianapolis, School of Science, Department of Psychology, Indianapolis, IN, USA.
bioRxiv. 2025 Jul 26:2025.07.22.666144. doi: 10.1101/2025.07.22.666144.
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 (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.
θ振荡——离散脑区同步活动的节律模式——已知可支持记忆、导航和行为协调,并且对药物操作敏感。急性乙醇(EtOH)暴露已被证明会改变θ振荡,但其对自然行为期间瞬态θ爆发和跨区域协调的影响仍不清楚。我们在腹腔注射EtOH(1.5 g/kg)或生理盐水后,记录了自由觅食小鼠内侧隔区(MS)、海马体(CA1)和内侧前额叶皮层(mPFC)的局部场电位(LFP)。我们分析了频谱功率、θ爆发动态、相位和滞后时间。来自CA1的爆发特征被用于训练机器学习分类器以预测实验条件。EtOH损害了运动能力并减少了目标导向行为,尤其是在实验早期。在CA1中,θ功率向较低频率转移,滞后相干性下降。EtOH增加了CA1中θ爆发的频率,但减少了其持续时间,而在MS中,只有爆发次数增加。EtOH增强了MS-CA1爆发对的时间对齐。耦合爆发期间CA1和MS之间的锁相仍然存在,但结构发生了改变。我们的分类器使用偏度和熵等爆发特征实现了强大的性能,并可靠地区分了治疗条件。EtOH通过改变θ爆发的时间和结构来调节隔海马动力学。这些结果表明,爆发水平特征是EtOH在自然行为期间对电路水平影响的敏感标志物。