Brain's Acetylcholine Directly Drives Sensory Learning, Not Just Opens the Gate

Neuromodulation by acetylcholine (ACh) plays a critical role in reshaping neural dynamics in the neocortex as a function of development, behavioral state, and learning. Prior work suggests cholinergic signaling can act as a gate for the subsequent induction of circuit plasticity. However, modification of ACh release could also be a direct mechanism for the expression of cortical plasticity.

To investigate this, scientists combined widefield and 2-photon imaging in head-fixed mice. They showed that visual fear conditioning leads to a selective, cue-dependent release of ACh in primary visual cortex that enhances visually-evoked neuronal responses via excitation of layer 1 GABAergic interneurons and resulting disinhibition of local excitatory pyramidal neurons.

Cholinergic signaling through muscarinic receptors in visual cortex was found to be necessary for both the enhanced visual response and conditioned fear behavior. The results demonstrate a novel capacity for conditioned release of ACh in sensory cortex to serve as a mechanism for sensory-guided behavioral learning. As lead author Moberly notes in the paper, "Rather than acting as a simple gate, cortical neuromodulation may thus play a central role in the expression of learned behavior."