@article{7ad367c7e3904b8ab689caabb007c743,
title = "Temporal and mosaic Tsc1 Deletion in the developing thalamus disrupts thalamocortical circuitry, neural function, and behavior",
abstract = "Tuberous sclerosis is a developmental genetic disorder caused by mutations in TSC1, which results inepilepsy, autism, and intellectual disability. The cause of these neurological deficits remains unresolved. Imaging studies suggest that the thalamus may be affected in tuberous sclerosis patients, but this has not been experimentally interrogated. We hypothesized that thalamic deletion of Tsc1 at distinct stages of mouse brain development would produce differential phenotypes. We show that mosaic Tsc1 deletion within thalamic precursors at embryonic day (E) 12.5 disrupts thalamic circuitry and alters neuronal physiology. Tsc1 deletion at this early stage is unique in causing both seizures and compulsive grooming in adult mice. In contrast, only a subset ofthese phenotypes occurs when thalamic Tsc1 is deleted at a later embryonic stage. Our findings demonstrate that abnormalities in a discrete population of neurons can cause global brain dysfunction and that phenotype severity depends on developmental timing and degree of genetic mosaicism",
author = "Normand, {Elizabeth A.} and Crandall, {Shane R.} and Thorn, {Catherine A.} and Murphy, {Emily M.} and Bettina Voelcker and Catherine Browning and Machan, {Jason T.} and Moore, {Christopher I.} and Connors, {Barry W.} and Mark Zervas",
note = "Funding Information: This work was supported by the Department of Defense Congressionally Directed Medical Research Program awards (W8 1XWH-11-1-0241 and W8 1XWH-12-1-0187, M.Z.). Additional personnel support includes: Brown Institute for Brain Science (E.A.N., C.I.M.), NIH NSGP training grant (NS062443-02, E.A.N.), NIH/NIMH Conte Center grant (P50 MH086400-03, B.W.C.), EFRI-BioSA/NSF (B.W.C.), and NIH (7-R01NS045130-08, C.I.M.). M.Z. and E.A.N. conceived of the project and wrote the manuscript. M.Z. oversaw all experiments and analysis. E.A.N. conducted and oversaw primary experiments and data analysis. S.R.C. conducted and analyzed whole-cell electrophysiology data with E.A.N. C.A.T. and E.M.M. conducted and analyzed LFPs. C.I.M. and B.W.C. consulted on electrophysiology experimental design and analysis. J.T.M. conducted biostatistics with E.A.N. and M.Z. C.B. analyzed grooming and seizures under the supervision of E.A.N. and M.Z. B.V. performed barrel analysis with E.A.N. and M.Z. Sensorimotor function was tested and analyzed by K. Bath ( http://rndb.clps.brown.edu ). We thank S. Cruikshank for his help with the lentiviral experiments. ",
year = "2013",
month = jun,
day = "5",
doi = "10.1016/j.neuron.2013.03.030",
language = "English (US)",
volume = "78",
pages = "895--909",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "5",
}