title: Developmental Sculpting of Intracortical Circuits by MHC Class I H2-Db and H2-Kb.
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.
authors.affiliation: Departments of Biology and Neurobiology and Bio-X.
authors.forename: Jaimie D
authors.initials: JD
authors.lastname: Adelson
authors.affiliation: Departments of Biology and Neurobiology and Bio-X.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Sapp
authors.affiliation: Departments of Biology and Neurobiology and Bio-X.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Brott
authors.affiliation: Departments of Biology and Neurobiology and Bio-X.
authors.forename: Hanmi
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Biology, Stanford University, Stanford, CA94305, USA.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Miyamichi
authors.affiliation: Department of Biology, Stanford University, Stanford, CA94305, USA.
authors.forename: Liqun
authors.initials: L
authors.lastname: Luo
authors.affiliation: Departments of Biology and Neurobiology and Bio-X.
authors.forename: Sarah
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Departments of Biology and Neurobiology and Bio-X.
authors.forename: Maja
authors.initials: M
authors.lastname: Djurisic
authors.affiliation: Departments of Biology and Neurobiology and Bio-X.
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Shatz
mesh_terms: D000818:Animals; D001369:Axons; D002540:Cerebral Cortex / Q000166:cytology* / Q000502:physiology*; D049229:Dendritic Spines; D019706:Excitatory Postsynaptic Potentials; D005805:Genes, MHC Class I; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity; D017966:Pyramidal Cells / Q000166:cytology* / Q000502:physiology*; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D014793:Visual Cortex / Q000166:cytology* / Q000502:physiology*
keywords: activity-dependent development; horizontal connections; major histocompatibility complex class I; modified rabies circuit tracing; visual cortex