Consequences of Developmental Defects in Somatosensory Map formation

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Summary The whisker-barrel system of mice is a popular neurobiological model for studies of neural mechanisms of pattern formation in the brain, activity-dependent refinement of connections, experience and use-dependent plasticity of cortical circuits, and sensory and cognitive deficits in mouse models of neurodevelopmental and disorders. One of the features that makes this system very attractive is that the patterned array of whiskers on the snout is represented by neural models at several levels of the somatosensory pathway. Over the past several decades, numerous studies demonstrated the importance of the sensory periphery and the intrinsic molecular cues of the thalamus and cortex in patterning of this system. We have been working on a unique mutant mouse model, where the periphery is intact, thalamic and cortical cues are intact but the ascending somatosensory pathway between the brainstem and thalamus is disrupted, leading to bilateral whisker map and pattern formation in the thalamus and cortex. Our studies during the current funding period revealed several morphological and behavioral phenotypes in this mouse line. Our continuation studies will have three aims: 1. To complete circuit mapping along the thalamocortical and corticocortical pathways in mice with trigeminothalamic axon guidance defects in the brainstem. We ask the following questions: How does the bifacial map in the SI cortex affect S1-M1 (primary motor cortex) and callosal connections? 2. To determine functional organization of “bifacial” responses in areas downstream of S1, and consequences on perceptual behavior. We will record electrophysiologically in vivo across cortical layers using 64-channel laminar silicon probe arrays. We will next conduct cellular-resolution calcium imaging from wM1 in awake mice to map downstream cortical consequences of the bifacial map. We will test the Krox20cre/Robo3lox/lox mice for whisker discrimination tasks with optogenetic silencing to probe brain’s use of bifacial map. 3. To determine the operating rules of critical period plasticity in this bifacial system. We ask the following questions: What are the characteristics of critical period plasticity in bilateral cortical maps in response to injury or sensory deprivation? How does unilateral sensory deprivation affect each of the maps in the cortex?