Focal control of thalamocortical gain shapes perception

In layer 4 of the primary sensory cortices, sensory data meets contextual information carried by multiple modulatory systems, establishing a point of control with powerful potential: what passes through this gate determines, for all downstream circuits, what exists in the world. Altering the processing state at even a small number of layer 4 thalamocortical synapses should be profoundly impactful on behavior. It is, however, often assumed—based on diffuse innervation of cortex by subcortical nuclei, and dense receptor expression in the association cortices—that the means by which modulatory systems powerfully alter cognition and behavior is through concurrent action across large swaths of tissue, mostly at ‘higher’ levels of cortex. Hypothesizing the converse—that highly localized modulatory changes to thalamocortical transmission could alter behavior—we used nicotine to selectively modify processing at a small proportion of thalamocortical synapses in macaque primary visual cortex, while recording across the full cortical depth. We observed widespread, heterogeneous changes in neuronal responses throughout all layers of cortex. The circuit apparently did not compensate for these changes, because they biased perceived contrast in a behavioral task. The pattern of neural and behavioral response changes we observed depended lawfully on stimulus position and orientation in a manner that could be accounted for by a normalization model with a tuned, multiplicative nicotine gain field. Significance In seeking to understand the role(s) neuromodulators play in cognition and behavior, answers are generally sought in the circuits of the association cortices, and neuromodulation is often conceived of, and modeled, in a manner akin to a coarse-grained—even cortex-wide—volume knob. Here, we show that focal cholinergic modulation of thalamocortical transmission in the visual system reshapes columnar neural activity and alters perceptual performance. Our observations suggest a modulatory architecture capable of precision control of thalamocortical transmission, and thus a previously underappreciated role for modulatory control of cortical gating.