Primary sensory cortex, the first point of sensory processing within the cerebral cortex, receives input from both a ?primary? and a ?secondary? thalamic nucleus. Primary thalamic nuclei relay signals from the external world to primary sensory cortex. In contrast, secondary thalamic nuclei are densely interconnected with many other cortical regions and may therefore be involved in more advanced computations. While the role of primary thalamic nuclei in sensory responses is well understood, secondary nuclei remain under-studied. Lesions in secondary thalamus render subjects unable to notice and choose important objects. These secondary thalamic nuclei may encode representations of behaviorally relevant objects (e.g. those predicting reward outcomes). The goal of this proposal is to determine what information is encoded in the projection from secondary thalamus to primary sensory cortex and how this input influences cortical responses. A well-characterized and genetically tractable model system, the mouse whisker system, will be used. In mice, the posterior medial nucleus (POm, somatosensory secondary thalamus) is in a promising position to influence neural activity in primary somatosensory cortex (S1). POm sends axons to layer 1 of S1, where it contacts S1 neurons at their apical dendrites, computationally powerful segments of cortical neurons. Input to the apical dendrites can strongly potentiate the firing of S1 neurons and has been proposed as a mechanism for feedback from higher cortex to modulate activity in sensory cortex. This thalamic input could increase S1 responses to behaviorally relevant objects. Indeed, many studies have shown that neural responses in primary sensory cortex across sensory systems are enhanced for relevant stimuli, such as attended, rewarded, or punishing stimuli. To test this hypothesis, we will first design a behavior that manipulates the behavioral relevance of objects. Next, the calcium imaging of POm axons within S1 will determine if POm inputs to S1 are biased towards relevant objects. Finally, optogenetic silencing of POm axons during juxtasomal recordings of S1 cells will test whether POm input enhances S1 representations of behaviorally relevant objects. These experiments will elucidate how the projection from secondary thalamus to sensory cortex imparts behavioral meaning to cortical sensory responses.

Public Health Relevance

This project aims to determine the normal function of the projection from ?secondary? thalamus to sensory cortex. Dysfunction of this and other circuits between thalamus and cortex underlies many common neurological disorders, including attention deficit hyperactivity disorder, epilepsy, and schizophrenia. Understanding how thalamocortical circuits function in the healthy brain is essential for identifying the aberrant conditions that appear in these neurological disorders and will hopefully lead to more effective diagnosis and treatment for patients.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZRG1)
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Gnadt, James W
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Columbia University (N.Y.)
Schools of Medicine
New York
United States
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