In these proposed Javits grant continuation studies, we focus directly on nine important, understudied aspects of cortical plasticity, in experiments that shall be conducted in primate and rodent models. First we shall define how the cortex creates-and expresses by the distributed responses of cortical neurons and by learning-based specialization of its processing machinery-sequence-dependent and context-dependent representation of complex acoustic and tactile inputs. Second, we shall further define how cortical plasticity is modulate separately and synergistically by cholinergic, dopaminergic, adrenegic and serotonergic control system that enable, and differentially amplify learning-induced cortical change. Third, we school further document, and compare and interrelate, behaviorally-driven vs. modulatroy -control-system/ acoustic-stimulation pairing-driven plasticity across the three dimension of cortical columns and minicolumns. Fourth, we shall define the spefic ways in which leaning-induced plasticity is modulated as a function of the predictability of inputs. Fifth, we shall further elaborate studies of """"""""catastrophic' plasticity, specificity, specifically studying forms that appear to arise in human populations as one probable cause of severe behavioral impairments. Sixth, we shall reconstruct the ontogeny if development of the cortical processing of complex acoustic inputs. Seventh, we shall develop animal models designed to test the hypothesis that signal-to-noise conditions that apply for the young cortex underlie the quality and the extent of the progressive refinement of its complex-signal processing machinery, and thereby largely account for variations in complex signal processing abilities (speech and language development, reading ability, """"""""intelligence"""""""") in human populations. Eighth, we shall define in detail, the ways in which plastic changes generated within """"""""secondary"""""""" cortical fields are derived from, or are independent of, the evolution of processing refinements in """"""""primary"""""""" sensory cortical areas. Ninth, these studies shall result in the development and elaboration of two new classes experimental models, designed to facilitate the study of molecular aspects of cortical plasticity mechanisms in mice, and the study of cellular and synaptic dynamics and plasticity in vitro experiments in rats. They experiments bare important implication for the further development of brain plasticity-based strategies for the remediation of neurological impairments, and for the amelioration of the symptoms of progressive neurological and psychiatric illness.
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