One of the most compelling and unresolved issues of visual processing is the role of the massive cortical feedback that occurs in a number of sites in the visual system. Activation of this feedback is thought to underlie processes such as attention. It may also serve as a partial solution to the binding problem, which has been proposed to rely on correlated firing in ensembles of neurons. The earliest cortical feedback does not occur in cortex at all, but in the thalamus. Similar to feedback systems in the cerebral cortex, corticothalamic feedback is characterized by extensive reentry of processed data from Layer 6 of cortex to lower processing levels in sensory thalamic nuclei such as the lateral geniculate nucleus (LGN). We propose to characterize the rules of communication between corticothalamic neurons and their target thalamic relays (e.g., what proportion of cells engage, and what patterns of activity promote this communication?);how might the resulting activity patterns within the thalamus be expressed topographically (e.g., does feedback promote certain types of activity in certain topographic regions and not others?);and how are the differences in these patterns critical in allowing certain kinds of information access to cortex (e.g., thalamic neurons have two firing regimes: burst and tonic, will these have differing impact at thalamocortical (TC) synapses?). Is information selectively affected in well-known physiological types of neurons? (e.g., ON/OFF, X/Y-like, and/or eye specific information?) To answer these questions, multielectrode arrays will be used to record thalamic ensembles and their ongoing dialog with Layer 6 of cortex. We will test the following hypotheses: (H1) that Layer 6 feedback to the LGN will produce correlations among ensembles of LGN cells that depend upon visuotopic register with spiking Layer 6 neurons;(H2) that LGN cells will preferentially activate Layer 6 neurons under certain firing conditions and activity patterns;and (H3) that brainstem activation will increase correlated firing across LGN neurons in response to Layer 6 feedback. The purpose of corticothalamic interactions is an enduring mystery, but one whose resolution will yield fundamental details of the defining role of feedback in neural systems. In addition to the details of normal corticothalamic processing, our proposed studies will provide a foundation for understanding abnormal thalamic network states in CNS disorders such as epilepsy, chronic pain and Parkinson's disease. Relevance: Information from peripheral sensory systems is processed at ascending stages of the thalamus and cortex. The cortex sends a massive projection back to lower processing levels of the brain, but the function of this feedback is poorly understood. This project proposes the detailed examination of how the cortex may instruct the thalamus to allow certain types of information to proceed to higher processing stages based on specific timing of stimulation or arrangement of objects in space. By recording from large numbers of brain cells in both regions simultaneously, we will discover rules that the regions use to communicate. These are perturbed in a number of brain disorders, thus the information we will learn about the basic rules of communication is vital for the understanding of these abnormal brain conditions.

National Institute of Health (NIH)
National Eye Institute (NEI)
Exploratory/Developmental Grants (R21)
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Cognitive Neuroscience Study Section (COG)
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Steinmetz, Michael A
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Wake Forest University Health Sciences
Anatomy/Cell Biology
Schools of Medicine
United States
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