Perceptual performance and V1 neural activity are exquisitely sensitive to small changes in thalamocortical gain

Neuromodulators powerfully shape circuit function via mechanisms that largely remain to be determined. As arguably the best-described cortical model system in neuroscience, the primary visual cortex (V1) of the rhesus monkey is an ideal model system to ask and answer these questions. There has been particular focus on acetylcholine actions in V1, where there is strong innervation from the basal forebrain and well-described local cholinergic anatomy in which β2 subunit-containing (high affinity) nicotinic receptors are strongly expressed on thalamocortical axons arriving in layer 4C. Activating these receptors strongly enhances local gain, but it is not known to what extent these effects propagate to other V1 layers. To determine the magnitude and direction (enhancement vs suppression) of gain effects outside layer 4C following gain injection via the nicotinic receptors on thalamic axons, we recorded across the cortical depth in V1 while selectively delivering nicotine locally to layer 4C. We observed widespread and heterogeneous gain effects across layers that could not be explained by visual stimulus conditions, but were well predicted by an adaptation of a normalization model. These gain changes were not compensated by the circuit, and thus were evident during performance of a perceptual task.