title: Experience-Dependent and Differential Regulation of Local and Long-Range Excitatory Neocortical Circuits by Postsynaptic Mef2c.
abstract: Development of proper cortical circuits requires an interaction of sensory experience and genetic programs. Little is known of how experience and specific transcription factors interact to determine the development of specific neocortical circuits. Here, we demonstrate that the activity-dependent transcription factor, Myocyte enhancer factor-2C (Mef2c), differentially regulates development of local versus long-range excitatory synaptic inputs onto layer 2/3 neurons in the somatosensory neocortex in vivo. Postnatal, postsynaptic deletion of Mef2c in a sparse population of L2/3 neurons suppressed development of excitatory synaptic connections from all local input pathways tested. In the same cell population, Mef2c deletion promoted the strength of excitatory inputs originating from contralateral neocortex. Both the synapse promoting and synapse suppressing effects of Mef2c deletion required normal whisking experience. These results reveal a role of Mef2c in experience-dependent development of specific sensory neocortical circuits.
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Kacey E
authors.initials: KE
authors.lastname: Rajkovich
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Kristofer W
authors.initials: KW
authors.lastname: Loerwald
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Carly F
authors.initials: CF
authors.lastname: Hale
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Carolyn T
authors.initials: CT
authors.lastname: Hess
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: jay.gibson@utsouthwestern.edu.
authors.forename: Jay R
authors.initials: JR
authors.lastname: Gibson
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: kimberly.huber@utsouthwestern.edu.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Huber
mesh_terms: D000818:Animals; D055785:Gene Knockdown Techniques; D064326:MEF2 Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D019579:Neocortex / Q000254:growth & development / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013003:Somatosensory Cortex / Q000254:growth & development / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D014738:Vibrissae
chemical_list: D064326:MEF2 Transcription Factors; C578041:Mef2c protein, mouse; D012333:RNA, Messenger
keywords: barrel cortex; connectivity; evoked; input pathway; local; long-range; spontaneous; synaptic transmission; transcription factor