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      Developmental Sculpting of Intracortical Circuits by MHC Class I H2-Db and H2-Kb

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          Abstract

          Synapse pruning is an activity-regulated process needed for proper circuit sculpting in the developing brain. Major histocompatibility class I (MHCI) molecules are regulated by activity, but little is known about their role in the development of connectivity in cortex. Here we show that protein for 2 MHCI molecules H2-Kb and H2-Db is associated with synapses in the visual cortex. Pyramidal neurons in mice lacking H2-Kb and H2-Db (KbDb KO) have more extensive cortical connectivity than normal. Modified rabies virus tracing was used to monitor the extent of pyramidal cell connectivity: Horizontal connectivity is greater in the visual cortex of KbDb KO mice. Basal dendrites of L2/3 pyramids, where many horizontal connections terminate, are more highly branched and have elevated spine density in the KO. Furthermore, the density of axonal boutons is elevated within L2/3 of mutant mice. These increases are accompanied by elevated miniature excitatory postsynaptic current frequency, consistent with an increase in functional synapses. This functional and anatomical increase in intracortical connectivity is also associated with enhanced ocular dominance plasticity that persists into adulthood. Thus, these MHCI proteins regulate sculpting of local cortical circuits and in their absence, the excess connectivity can function as a substrate for cortical plasticity throughout life.

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          Author and article information

          Journal
          Cereb Cortex
          Cereb. Cortex
          cercor
          cercor
          Cerebral Cortex (New York, NY)
          Oxford University Press
          1047-3211
          1460-2199
          April 2016
          14 October 2014
          1 April 2017
          : 26
          : 4
          : 1453-1463
          Affiliations
          [1 ] Departments of Biology and Neurobiology and Bio-X
          [2 ] Department of Biology, Stanford University , Stanford, CA 94305, USA
          Author notes
          Address correspondence to Jaimie D. Adelson, 318 Campus Drive W1.1, Stanford, CA 94305, USA. Email: jaimie.adelson@ 123456gmail.com ; Carla J. Shatz. 318 Campus Drive W1.1, Stanford, CA 94305, USA. Email: cshatz@ 123456stanford.edu
          Article
          PMC4785944 PMC4785944 4785944 bhu243
          10.1093/cercor/bhu243
          4785944
          25316337
          f3ce18ac-69e1-42a8-bc88-0033613e74d2
          © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com
          History
          Categories
          Original Articles

          modified rabies circuit tracing,activity-dependent development,horizontal connections,major histocompatibility complex class I,visual cortex

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