Experience- and activity-dependent transcription is a candidate mechanism to mediate development and refinement of specific cortical circuits. Here, we demonstrate that the activity-dependent transcription factor myocyte enhancer factor 2C (MEF2C) is required in both presynaptic layer (L) 4 and postsynaptic L2/3 mouse (male and female) somatosensory (S1) cortical neurons for development of this specific synaptic connection. While postsynaptic deletion of Mef2c weakens L4 synaptic inputs, it has no effect on inputs from local L2/3, contralateral S1, or the ipsilateral frontal/motor cortex. Similarly, homozygous or heterozygous deletion of Mef2c in presynaptic L4 neurons weakens L4 to L2/3 excitatory synaptic inputs by decreasing presynaptic release probability. Postsynaptic MEF2C is specifically required during an early postnatal, experience-dependent, period for L4 to L2/3 synapse function, and expression of transcriptionally active MEF2C (MEF2C-VP16) rescues weak L4 to L2/3 synaptic strength in sensory-deprived mice. Together, these results suggest that experience- and/or activity-dependent transcriptional activation of MEF2C promotes development of L4 to L2/3 synapses. Additionally, MEF2C regulates the expression of many pre- and postsynaptic genes in postnatal cortical neurons. Interestingly, MEF2C was necessary for activity-dependent expression of many presynaptic genes, including those that function in transsynaptic adhesion and neurotransmitter release. This work provides mechanistic insight into the experience-dependent development of specific cortical circuits.

经验和活动依赖性转录是介导特定皮质回路发育和细化的候选机制。在这里，我们证明活性依赖性转录因子肌细胞增强因子 2C （MEF2C） 在突触前层 （L） 4 和突触后 L2/3 小鼠 （雄性和雌性） 体感 （S1） 皮层神经元中都需要这种特异性突触连接的发育。虽然 Mef2c 的突触后缺失削弱了 L4 突触输入，但它对来自局部 L2/3、对侧 S1 或同侧额叶/运动皮层的输入没有影响。同样，突触前 L4 神经元中 Mef2c 的纯合或杂合缺失通过降低突触前释放概率来削弱 L4 到 L2/3 兴奋性突触输入。突触后 MEF2C 在出生后早期、经验依赖性时期特别需要 L4 至 L2/3 突触功能，转录活性 MEF2C （MEF2C-VP16） 的表达可挽救感觉剥夺小鼠的 L4 至 L2/3 突触强度较弱。总之，这些结果表明 MEF2C 的经验和/或活性依赖性转录激活促进了 L4 到 L2/3 突触的发育。此外，MEF2C 调节出生后皮层神经元中许多突触前和突触后基因的表达。有趣的是，MEF2C 对于许多突触前基因的活性依赖性表达是必需的，包括那些在跨突触粘附和神经递质释放中起作用的基因。这项工作为特定皮质回路的经验依赖性发展提供了机制见解。