Visuomotor integration and visuomotor skill learning depend on local plasticity in visual cortex during development

Visuomotor experience shapes responses in visual cortex during development. Coupling between movement and visual feedback establishes a comparator circuit between top-down and bottom-up inputs in layer 2/3 of mouse primary visual cortex (V1). Such a circuit is capable of computing prediction error responses in layer 2/3 excitatory neurons in V1. Given that visual cortex receives both the bottom-up visual input and signals consistent with a top-down prediction of visual flow given movement, it has been speculated that visual cortex is a site of integration of these two signals. If correct, we would predict that perturbing plasticity in V1 during development should prevent the establishment of a normal balance between bottom-up and top-down input, and consequently an impairment of visuomotor prediction errors in layer 2/3 neurons of primary visual cortex.
In Chapter I, we tested whether local plasticity in visual cortex is necessary for the establishment of this balance by locally perturbing neural plasticity. Our results show that perturbing NMDA receptor-dependent plasticity during development of the visual system leads to a reduction in visuomotor prediction error responses, and that plasticity in V1 is crucial for the development of normal visuomotor integration.
In Chapter II, we further investigated the balance of top-down and bottom-up inputs in V1 and ask, given that pro-psychotic agents (e.g., hallucinogens) can influence visual cortex activity, whether antipsychotic drugs also induce common circuit changes. We investigated three antipsychotic drugs: Haloperidol, Clozapine and Aripiprazole, with the aim of identifying a common functional signature, possibly underpinning their clinical efficacy. The most common change was a decrease in visuomotor prediction errors in layer 2/3 neurons. Clozapine, as one of most effective drugs, decreased activity of inhibitory neurons thought to mediate visual feedforward signals and increased the mean activity in layer 5. Overall, however, we did not find common changes in all of these three antipsychotic drugs.