Cholinergic innervation is necessary to shift reward timing activity in rodent visual cortex

Abstract

While the biological analogue of prediction error has been well characterized in the midbrain dopaminergic system, the possibility of other neuromodulatory systems acting as global reinforcers is a topic of much debate. Reward timing, the phenomenon by which single unit responses in primary visual cortex (V1)
reflect an operantly learned stimulus‐reward interval, offers a tractable preparation to investigate reinforcement learning in vivo: theoretical work suggests that reward timing results from the interaction of stimulus‐evoked recurrent network activity and a global reinforcement signal that indicates the time of
received reward. We hypothesized that this signal is conveyed by cholinergic neurons arising from the basal forebrain (BF), a strong candidate system that projects globally to most cortical regions, has a known role in plasticity, and is involved in attention and the representation of salience. To test the necessity of such a signal in entraining reward timing in V1, rats were trained on an initial stimulus‐reward contingency, received a neurotoxin in V1 that eliminated BF cholinergic terminals, and subsequently trained on a second contingency. We found that extracellular single unit recordings from V1 of lesioned animals, but not saline‐infused controls, failed to show shifted neural reports of reward that matched the new contingency. Importantly, neurons of
lesioned animals continued to display intervals associated with the initial contingency, arguing that cholinergic input is required to learn, but not to express, reward timing activity