Cortical acetylcholine dynamics are predicted by cholinergic axon activity and behavior state

Area of Science:

• Neuroscience
• Neurochemistry

Background:

• Acetylcholine (ACh) is implicated in rapid, spontaneous brain-state transitions during wakefulness.
• The precise spatiotemporal dynamics of cortical ACh during these transitions remain largely unknown.

Purpose of the Study:

• To investigate the spatiotemporal characteristics of cortical acetylcholine activity during brain-state transitions in awake animals.
• To correlate ACh dynamics with behavioral states like locomotion and pupil dilation.

Main Methods:

• Simultaneous in vivo imaging of GRAB-ACh sensors and GCaMP-expressing basal forebrain axons.
• Behavioral tracking, including locomotion and pupil size monitoring.
• Computational deconvolution of sensor signals and predictive modeling.

Main Results:

• High correlation observed between basal forebrain axon activity and cortical GRAB-ACh signals during locomotion and pupil dilation.
• Cortical ACh levels were predictable from axonal activity, with local ACh decreasing with distance from active axons.
• Deconvolution revealed rapid clearance of small ACh transients, and a predictive model generalized well to unseen data.

Conclusions:

• Cortical ACh release is tightly linked to specific behavioral states and originates from basal forebrain projections.
• The study provides a detailed spatiotemporal map of ACh signaling during dynamic brain state changes.
• Findings enhance understanding of neuromodulation's role in cognitive processes and brain state regulation.