Alternate pathways for the spread of excitation:Functional and behavioral studie

Columbia University Health Sciences, New York NY

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Abstract

DESCRIPTION (provided by applicant): An essential step in understanding sensory processing is to identify the synaptic circuitry underlying its neural representation. Aberrant network activity that disrupts excitation-inhibition balance can have severe consequences, contributing to the development of epilepsy, schizophrenia or Parkinson's disease. Identifying the mechanisms for the spread of excitation will directly inform about potential abnormalities that arise under pathological conditions. Thalamic projections to cortical layer 4 (L4) are the primary pathway by which sensory information enters the cortex via the thalamus. Information is thought to flow along a hierarchical series of connections from L4 to superficial L2/3, to the output cells in L5/6. However, thalamic neurons send sparse projections to virtually all layers of cortex, notably to the L5/L6 border. Mechanisms may exist that render sparse projections, often ignored in the study of circuits, highly effective in spreading excitatory activity. This would suggest a more complex mechanism of sensory information processing than previously thought, by which information relayed by thalamus reaches cortical output neurons via direct parallel pathways. Using optogenetics, electrophysiology, and behavioral paradigms, we propose to demonstrate that direct thalamocortical inputs can strongly, and directly drive L5 output neurons without L4 activity, and determine how the direct and indirect pathways affect sensory behavior.