Abstract
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.
Highlights
We first quantified the effect of a conditional knockout of NMDA receptors in V1 prior to first visual experience on the responses of layer 2/3 (L2/3) V1 neurons
Mice were trained in this setup for 2 hours every other day for 12 days, after which we measured calcium activity in L2/3 neurons using two-photon imaging (Figure 1C)
Similar to the responses observed in ΔGrin1juv mice, we found that in mice that expressed photoactivatable autocamtide inhibitory peptide 2 (paAIP2) in excitatory neurons under the CaMKIIα(1.3kb)-promoter, the strongest changes were in mismatch and visual responses, while running onset responses were less affected (Figures 6C-6E)
Summary
The brain learns this transformation from motor output to sensory feedback. These transformations between different coding coordinate systems are referred to as internal models and are essential for the capacity of using sensory input to guide movements (Jordan and Rumelhart, 1992). When raised without coupling between movements and sensory feedback during visual development, kittens fail to use visual input to guide movements (Held and Hein, 1963). When kittens are reared with a neck collar that prevents them from seeing the effect of moving their paws independently, but allows them to see the effect of extending their paws while standing, they have normal visualapproach paw-extension reflexes, but fail to perform visually guided reaches (Hein and Held, 1967)
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