Experience-Dependent and Differential Regulation of Local and Long-Range Excitatory Neocortical Circuits by Postsynaptic Mef2c

• Published in: Neuron (Cambridge, Mass.) Vol. 93; no. 1; pp. 48 - 56
• Main Authors: Rajkovich, Kacey E., Loerwald, Kristofer W., Hale, Carly F., Hess, Carolyn T., Gibson, Jay R., Huber, Kimberly M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.01.2017; Elsevier Limited
• Subjects: Animals; Autism; barrel cortex; connectivity; evoked; Gene Knockdown Techniques; Genomics; input pathway; local; long-range; MEF2 Transcription Factors - genetics; MEF2 Transcription Factors - metabolism; Mice; Mice, Knockout; Neocortex - growth & development; Neocortex - metabolism; Neurons; Neurons - metabolism; Pyramidal Cells - metabolism; RNA, Messenger - metabolism; Schizophrenia; Somatosensory Cortex - growth & development; Somatosensory Cortex - metabolism; spontaneous; Synapses - metabolism; synaptic transmission; transcription factor; Transcription factors; Vibrissae; barrel cortex; evoked; transcription factor; connectivity; long-range; input pathway; synaptic transmission; spontaneous; local
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2016.11.022

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. •Postsynaptic MEF2C differentially regulates distinct inputs onto L2/3 neurons•MEF2C increases the number of local excitatory inputs onto L2/3 neurons•MEF2C suppresses the strength of long-range excitatory cortical L2/3 inputs•Experience-dependent development of excitatory L2/3 inputs requires MEF2C Rajkovich et al. demonstrate that postsynaptic MEF2C cell-autonomously mediates experience-dependent neocortical circuit development via bidirectional regulation of local and long-range excitatory synaptic inputs onto L2/3 pyramidal neurons, linking activity-dependent transcription to plasticity at specific synaptic circuits in vivo.