Presentation Details
Behavioral State and Ethological Salience Shape HDB Cholinergic Activity During Naturalistic Olfactory Exploration

Kelsey R.Glasper, Max L.Fletcher.

University of Tennessee Health Science Center, Memphis, TN, USA

Abstract


Basal forebrain cholinergic signaling is widely implicated in attention, arousal, and sensory processing. Studies using operant paradigms demonstrate rapid cholinergic fluctuations during task engagement, yet these approaches primarily capture population-level neuromodulatory signals driven by explicit cues and reward contingencies. Consequently, how identified cholinergic neurons in the horizontal limb of the diagonal band of Broca (HDB) are engaged during self-directed olfactory exploration outside trained behavioral frameworks remains poorly understood.To address this gap, we expressed GCaMP8f in cholinergic neurons of the HDB in ChAT-Cre mice and performed miniscope imaging as animals freely explored an environment containing social or non-social odors across multiple days. Rather than aligning neural activity to odor onset or task epochs, we used ethogram-based annotation to define investigative bouts, behavioral transitions, and non-investigatory states during natural exploration.We find that HDB cholinergic activity is structured by behavioral engagement, with elevated activity during investigative bouts and transitions into investigation. During odor sampling, HDB populations exhibit investigation-locked responses and odor-category-dependent ensemble coordination that dissociates familiarity from ethological salience. Familiar stimuli, such as bedding, elicited strong and coordinated responses, while response magnitude declined across days with environmental familiarization but remained elevated during re-engagement. Together, these findings indicate that HDB cholinergic activity during olfactory behavior reflects state-dependent modulation shaped by self-directed investigative structure rather than stimulus identity or task demands alone.

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