Locomotion-induced gain of visual responses cannot explain visuomotor mismatch responses in layer 2/3 of primary visual cortex.

The aim of this work is to provide a comment on a recent paper by Muzzu and Saleem (2021), which claims that visuomotor mismatch responses in mouse visual cortex can be explained by a locomotion-induced gain of visual halt responses. Our primary concern is that without directly comparing these responses with mismatch responses, the claim that one response can explain the other appears difficult to uphold, more so because previous work finds that a uniform locomotion-induced gain cannot explain mismatch responses. To support these arguments, we analyze layer 2/3 calcium imaging datasets and show that coupling between visual flow and locomotion greatly enhances mismatch responses in an experience-dependent manner compared with halts in non-coupled visual flow. This is consistent with mismatch responses representing visuomotor prediction errors. Thus, we conclude that while feature selectivity might contribute to mismatch responses in mouse visual cortex, it cannot explain these responses.

NMDA receptors in visual cortex are necessary for normal visuomotor integration and skill learning.

The experience of coupling between motor output and visual feedback is necessary for the development of visuomotor skills and shapes visuomotor integration in visual cortex. Whether these experience-dependent changes of responses in V1 depend on modifications of the local circuit or are the consequence of circuit changes outside of V1 remains unclear. Here, we probed the role of N-methyl-d-aspartate (NMDA) receptor-dependent signaling, which is known to be involved in neuronal plasticity, in mouse primary visual cortex (V1) during visuomotor development. We used a local knockout of NMDA receptors and a photoactivatable inhibition of CaMKII in V1 during the first visual experience to probe for changes in neuronal activity in V1 as well as the influence on performance in a visuomotor task. We found that a knockout of NMDA receptors before, but not after, first visuomotor experience reduced responses to unpredictable stimuli, diminished the suppression of predictable feedback in V1, and impaired visuomotor skill learning later in life. Our results demonstrate that NMDA receptor-dependent signaling in V1 is critical during the first visuomotor experience for shaping visuomotor integration and enabling visuomotor skill learning.