Understanding the phenomena of adult brain plasticity, triggered either by injury to the nervous system or by learning new skills, will likely provide a fundamental step towards establishing newtherapies for treating neurological disorders. However, the circuit mechanisms underlying neural plasticity remain mostly unknown. Elucidating this question is the central focus of our research program. During the previous funding period, we demonstrated that corticothalamic (CT) projections, originating in the rat primary somatosensory cortex (S1), significantly contribute to the definition of the spatiotemporal structure of the receptive fields of neurons in the ventroposterior medial nucleus (VPM) of the thalamus. Our data also revealed that, following a peripheral deafferentation, CT projections contribute to the ability of VPM neurons to exhibit plastic reorganization. Interestingly, we also found that both the magnitude and duration of tactile responses of S1 and VPM neurons change according to the animal's behavioral state. Together, these results indicate that sensory representations within the thalamocortical loop (TCL) are plastic, dynamically modulated constructs, which emerge from the asynchronous convergence of multiple ascending and descending excitatory and inhibitory afferents. Most recently, we have reported that tactile signal processing across S1 layers is fundamentally different during active versus passive tactile stimulation. For example, task-related modulation of firing rates can begin before tactile stimulation. To date, however, the circuit mechanisms to account for such gross changes in response properties remain largely unknown. Here we propose to test the hypothesis that, during active tactile exploration, multiple corticocortical and corticothalamic projections dynamically modulate the magnitude and duration of tactile responses of S1 and VPM neurons respectively, in order to optimize the discrimination of tactile stimuli. We also propose that learning of a new tactile discrimination task enhances the effects of these """"""""top-down"""""""" projections on the TCL. In this project we propose to focus on two major inputs to S1: primary motor cortex (M1) and contralateral S1. Focal reversible inactivation of M1 or S1 would reveal their contribution to TCL responses during motivated discrimination behavior. Chronic recording methods would allow us to follow changes in response statistics over the course of learning the discrimination task. Moveable electrode technology, pioneered in our lab, enables us to correlate the layer structure of S1 responses with anatomically known projections. These experiments offer a window into the nervous system as it dynamically integrates widely distributed neural signals to carry out a non-trivial sensory-motor task, and promise significant revisions to current models of sensation based predominantly on electrophysiological responses to passively delivered stimuli.
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