The potential for functional reorganization of the adult neocortex is now widely recognized. Our research has shown that the motor cortex (MI) of adult rats can reorganize rapidly following peripheral nerve lesions or changes in limb configuration. Changes in the balance of excitatory and inhibitory connections within MI can unmask latent connections and produce new output representations that resemble those formed after peripheral manipulations. Our preliminary data indicate that horizontal connections of MI undergo activity-dependent, long term synaptic modification. Thus, intracortical horizontal connections appear to form a substrate through which synaptic plasticity mechanisms can produce rapid modification of the functional architecture of the motor cortex. The present study will further test this hypothesis and address three questions related to the sites and mechanisms of cortical synaptic plasticity using extracellular field potential and intracellular recordings methods in MI slices. 1. Is activity dependent synaptic modification restricted to specific sets of horizontal Intracortical connections? We will test the hypothesis that high frequency (tetanic) stimulation during reduced inhibition induces potentiation of deep as well as superficial horizontal connections. The cell types involved in this form of modification will also be identified 2. Do associative mechanisms permit synaptic modification at additional cortical sites? We will investigate whether synaptic modification induced by pairing of synaptic input at low rates with intracellular depolarization provides an additional route for potentiation at different cortical sites. 3. Do high and low frequency-induced synaptic modifications operate by different mechanisms? Next, the hypothesis that synaptic strength changes operate at different sites in motor cortex by NMDA- or Ca++ -dependent mechanisms, upon different cells types, or under different conditions of induction will be tested. 4. Do neuromodulators gate potential sites of synaptic modification? The hypothesis that sites of synaptic modification can be regulated by cholinergic inputs will be tested. These studies will show that synaptic plasticity can operate through horizontal cortical connections to restructure the functional architecture of the motor cortex. They will also provide direct evidence for intracortical mechanisms for MI plasticity. These studies will have important consequences not only for understanding how the cortex functions as an information processing and storage structure, but may also provide insight in how disrupted motor cortical circuits may contribute to movement disorders or how they may be manipulated to promote recovery of function after damage.
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