Outcome-locked cholinergic signaling suppresses prefrontal encoding of
stimulus associations

Gaqi Tu, Adel Halawa, Xiao Tian Yu, Samuel Gillman, Kaori Takehara-Nishiuchi, Journal of Neuroscience.


Drugs compensating for the decline of acetylcholine (ACh) are used for cognitive impairment such as Alzheimer’s disease (AD). However, their beneficial effects are limited, demanding new strategies based on better understandings of how ACh modulates cognition. Here, we report that by manipulating ACh signals in the medial prefrontal cortex, we can control the strength of aversive associative learning in mice. Specifically, the suppression of ACh signals during an aversive outcome facilitated its association with a preceding cue. In contrast, the suppression of ACh signals during the cue impaired learning. Considering that this paradigm depends on the brain regions affected in AD, our findings indicate that precisely timed control of ACh signals is essential to refine ACh-based strategies for cognitive enhancement.


New discovery