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?

Public Health Relevance

Sensory maps of each brain hemisphere process information from the opposite side of the body. Congenital defects in somatosensory pathways result in an abnormal map formation in the cortex. We will investigate the development and plasticity of a bilateral facial map in the cortex and how it is incorporated into the rest of the corticocortical circuitry.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS084818-07
Application #
10110032
Study Section
Somatosensory and Pain Systems Study Section (SPS)
Program Officer
Gnadt, James W
Project Start
2014-02-01
Project End
2025-02-28
Budget Start
2021-03-01
Budget End
2022-02-28
Support Year
7
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Kwon, Sung Eun; Tsytsarev, Vassiliy; Erzurumlu, Reha S et al. (2018) Organization of orientation-specific whisker deflection responses in layer 2/3 of mouse somatosensory cortex. Neuroscience 368:46-56
Mueller, Bernhard J; Zhdanov, Alexander V; Borisov, Sergey M et al. (2018) Nanoparticle-based fluoroionophore for analysis of potassium ion dynamics in 3D tissue models and in vivo. Adv Funct Mater 28:
Iwasato, Takuji; Erzurumlu, Reha S (2018) Development of tactile sensory circuits in the CNS. Curr Opin Neurobiol 53:66-75
Renier, Nicolas; Dominici, ChloƩ; Erzurumlu, Reha S et al. (2017) A mutant with bilateral whisker to barrel inputs unveils somatosensory mapping rules in the cerebral cortex. Elife 6:
Tsytsarev, Vassiliy; Arakawa, Hiroyuki; Zhao, Shuxin et al. (2017) Behavioral Consequences of a Bifacial Map in the Mouse Somatosensory Cortex. J Neurosci 37:7209-7218
Tang, Qinggong; Lin, Jonathan; Tsytsarev, Vassiliy et al. (2017) Review of mesoscopic optical tomography for depth-resolved imaging of hemodynamic changes and neural activities. Neurophotonics 4:011009
Tsytsarev, Vassiliy; Akkentli, Fatih; Pumbo, Elena et al. (2017) Planar implantable sensor for in vivo measurement of cellular oxygen metabolism in brain tissue. J Neurosci Methods 281:1-6
Nag, Okhil K; Stewart, Michael H; Deschamps, Jeffrey R et al. (2017) Quantum Dot-Peptide-Fullerene Bioconjugates for Visualization of in Vitro and in Vivo Cellular Membrane Potential. ACS Nano 11:5598-5613
Tang, Qinggong; Tsytsarev, Vassiliy; Frank, Aaron et al. (2016) In Vivo Mesoscopic Voltage-Sensitive Dye Imaging of Brain Activation. Sci Rep 6:25269
Tsytsarev, Vassiliy; Pumbo, Elena; Tang, Qinggong et al. (2016) Study of the cortical representation of whisker frequency selectivity using voltage-sensitive dye optical imaging. Intravital 5:e1142637

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