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Multi-layer Cortical Ca2+ Imaging in Freely Moving Mice with Prism Probes and Miniaturized Fluorescence Microscopy

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A cholinergic mechanism orchestrating task-dependent computation across the cortex.

Jiaqi Keith Luo, Junhua Tan, Erin Myhre

Biorxiv : the Preprint Server for Biology

|December 15, 2025

Summary

This summary is machine-generated.

Acetylcholine release in the cortex orchestrates brain activity for specific tasks. This neuromodulator is crucial for evidence accumulation during decision-making, highlighting its role in cognitive flexibility.

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Area of Science:

Neuroscience
Cognitive Science
Cholinergic Systems

Background:

Animals must adapt cognitive processes for different tasks in dynamic environments.
Cortical neural activity dynamics are influenced by task demands and behavioral strategies.
The circuit mechanisms orchestrating task-dependent cortical dynamics remain largely unknown.

Purpose of the Study:

To investigate the role of acetylcholine release in the cortex in orchestrating task-dependent neural dynamics.
To test the hypothesis that the basal forebrain cholinergic system is key to cognitive flexibility.
To elucidate the function of cholinergic input in evidence accumulation during decision-making.

Main Methods:

Imaged cholinergic axons in the cortex of mice performing distinct virtual reality decision-making tasks.
Analyzed spatiotemporal patterns of cholinergic activity in relation to task demands and strategy.
Used optogenetics to silence cholinergic terminals and assess causal effects on cortical activity and behavior.

Main Results:

Cholinergic input to the cortex is heterogeneous, multiplexing various signals in a task-dependent manner.
Cholinergic activity specifically encoded an evidence-dependent decision variable during evidence accumulation.
Silencing cholinergic terminals selectively impaired evidence accumulation and cortical coding during this task.

Conclusions:

Identified a novel cholinergic mechanism orchestrating cortex-wide activity for task-specific computations.
Cholinergic system plays a causal role in evidence accumulation and decision-making processes.
Cholinergic input is a key node in brain networks supporting cognitive flexibility and sensory evidence integration.