The principal objective of this Javits' Grant renewal research will be to document the distributed, selective responses of cortical neurons and cortical cell assemblies driven to change by training adult monkeys at simple spatial, temporal and time-sequenced behaviors at which these monkeys' behaviorally measured capabilities progressively improve with practice. These studies constitute a direct investigation of cortical network mechanisms that account for its contributions to learning and nondeclarative memory. Studies conducted in the current grant period have shown that the adaptive operations of the cortical network machinery can only be understood by their study on the level of distributed representations across the behaviorally engaged cortical sector. That is the case because a) behaviorally important inputs drive changes in positively coupled cortical cell assemblies that can only be reconstructed from a fine-grained, distributed sample; and because b) we have been able to account for gains in discrimination abilities with training only by reconstructing selective neuronal responses all across the cortical network region engaged by behaviorally important inputs. In continuation, we shall more intensively apply chronic recording methods that have been developed in the current grant period to derive a dense neuron response sample (100- 150 micron interelectrode spacing) over 0.5-1.0mm2 cortical zones. These chronic dense-sample microelectrode recording arrays will be implanted in adult monkeys or marmosets who have been trained in a somatosensory or auditory behavioral task, respectively. With the arrays in place and after a baseline period, the learned behavior will be shifted to previously untrained skin locations or frequencies that directly engage the cortical network sector being sampled. The distributed a) selective responses of cortical neurons, b) responses to behaviorally important stimuli, c) changes in coupling of neurons forming dynamic cortical cell assemblies, and d) responses related to behavioral contingencies will all be tracked day by day. Cortical network sectors in somatosensory cortical fields 3b and 1 and in the primary auditory cortical field A-1 will be challenged by stimuli varying systematically in their spatial, temporal and intensive structures, as well as by simple temporally-sequenced, continuously-moving and apparently-moving somatosensory stimuli and (from the perspective of these cortical networks) their auditory time-varying spectral equivalents. These studies are among the most important to be conducted in integrative neuroscience because they strike directly at determining the fundamental processes in the neocortex that underlie its contributions to behavior. They provide a direct challenge to conventional studies of these cortical areas, and should contribute significantly to carrying studies in these sensory domains to a higher and more effective experimental level. As dynamic machinery of the neocortex comes to be progressively better understood, we gain progressively deeper insights into the functional illnesses attributable to its malfunction, and into its remarkable capacities for functional self-repair. And as these basic cortical network response data come from these studies, we are refining neural network models that will almost certainly evolve into the general theory of neocortical function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS010414-20
Application #
3394237
Study Section
Hearing Research Study Section (HAR)
Project Start
1978-07-01
Project End
1995-12-31
Budget Start
1992-01-10
Budget End
1992-12-31
Support Year
20
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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de Villers-Sidani, Etienne; Simpson, Kimberly L; Lu, Y-F et al. (2008) Manipulating critical period closure across different sectors of the primary auditory cortex. Nat Neurosci 11:957-65
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