Moghadam Fatemeh Farokhi, Gutierrez Guzman Blanca E, Zheng Xihui, Parsa Mina, Hozyen Lojy M, Dannenberg Holger
Department of Bioengineering, George Mason University, Fairfax, VA, United States.
Interdisciplinary Program for Neuroscience, George Mason University, Fairfax, VA, United States.
bioRxiv. 2025 Jan 21:2025.01.21.634097. doi: 10.1101/2025.01.21.634097.
In the hippocampal formation, cholinergic modulation from the medial septum/diagonal band of Broca (MSDB) is known to correlate with the speed of an animal's movements at sub-second timescales and also supports spatial memory formation. Yet, the extent to which sub-second cholinergic dynamics, if at all, align with transient behavioral and cognitive states supporting the encoding of novel spatial information remains unknown. In this study, we used fiber photometry to record the temporal dynamics in the population activity of septo-hippocampal cholinergic neurons at sub-second resolution during a hippocampus-dependent object location memory task using ChAT-Cre mice. Using a general linear model, we quantified the extent to which cholinergic dynamics were explained by changes in movement speed, behavioral states such as locomotion, grooming, and rearing, and hippocampus-dependent cognitive states such as recognizing a novel location of a familiar object. The data show that cholinergic dynamics contain a multiplexed code of fast and slow signals i) coding for the logarithm of movement speed at sub-second timescales, ii) providing a phasic spatial novelty signal during the brief periods of exploring a novel object location, and iii) coding for environmental novelty at a seconds-long timescale. Furthermore, behavioral event-related phasic cholinergic activity around the onset and offset of the behavior demonstrates that fast cholinergic transients help facilitate a switch in cognitive and behavioral state before and during the onset of behavior. These findings enhance understanding of the mechanisms by which cholinergic modulation contributes to the coding of movement speed and encoding of novel spatial information.
在海马结构中,来自内侧隔核/布罗卡斜带(MSDB)的胆碱能调制已知在亚秒级时间尺度上与动物运动速度相关,并且还支持空间记忆形成。然而,亚秒级胆碱能动态在多大程度上(如果有的话)与支持新空间信息编码的瞬时行为和认知状态相一致,仍然未知。在本研究中,我们使用光纤光度法,在一项依赖海马体的物体位置记忆任务中,以亚秒级分辨率记录ChAT-Cre小鼠海马-隔区胆碱能神经元群体活动的时间动态。使用一般线性模型,我们量化了胆碱能动态在多大程度上可以由运动速度变化、诸如运动、梳理和直立等行为状态以及诸如识别熟悉物体的新位置等依赖海马体的认知状态来解释。数据表明,胆碱能动态包含快速和慢速信号的多重编码:i)在亚秒级时间尺度上编码运动速度的对数;ii)在探索新物体位置的短暂时期提供相位性空间新奇信号;iii)在长达数秒的时间尺度上编码环境新奇性。此外,行为发作和结束周围与行为事件相关的相位性胆碱能活动表明,快速胆碱能瞬变有助于在行为发作之前和期间促进认知和行为状态的转换。这些发现增进了我们对胆碱能调制有助于运动速度编码和新空间信息编码的机制的理解。