SPATIOTEMPORAL ORGANIZATION OF CHOLINERGIC INPUT IN THE SOMATOSENSORY CORTEX DURING TACTILE DETECTION

Understanding how the brain detects sensory inputs is a key challenge in neuroscience. Brain states exert a powerful and dynamic influence over perception, with neuromodulatory systems playing a crucial role in regulating brainstates. The perceptual threshold varies with behavioral state, experience, and mood. However, the mechanisms controlling this threshold remain largely unknown.

Previous studies have demonstrated that cholinergic inputs modulate cortical activity, influencing the detection of sensory stimuli. Neuromodulation was thought to have a widespread and uniform impact throughout the brain. However, anatomical evidence suggests that cholinergic neurons offer targeted innervation to different cortical regions, potentially leading to differences in activity patterns.

Here, we characterize the spatiotemporal organization of cholinergic activity in the somatosensory cortex of mice engaged in tactile detection. We tested the role of S1 cholinergic activity in the mouse's sensitivity to detect tactile stimuli. By using a cholinergic sensor we were able to image cholinergic activity across the S1 during the task. We observed cholinergic activity decreasing prior to the onset of the stimulus to successful detection. These patterns in the pre-stimulus window were highly predictive of behavioral outcome. Spatiotemporal patterns of cholinergic activity remained largely unchanged across behavioral tests where mice had to detect the stimulations from different body parts, indicating that the cholinergic activity leading to detection is independent of the specific body part attended to.

Together, these results paint a complex picture for cholinergic dynamics in the cortex, suggesting it works at mesoscale, not a single global signal but not fully local either.