Regulation of Barrel Cortex Plasticity

皮层神经元形成突触回路以完成大脑皮层的复杂功能。在早期发育过程中，回路的形成涉及由转录因子调控的内在遗传程序和来自突触输入的外在活性依赖性过程的相互作用。为了确定转录因子在调节活动依赖性神经元特性变化中的功能，我们建议在这里使用啮齿动物桶皮质作为模型来研究Lhx2（一种LIM同源结构域转录因子）在调节桶皮质可塑性中的功能。小鼠大脑初级体感皮层（S1）的桶状皮层是研究皮层回路形成的理想系统。桶皮质在地形上组织成第4层（L4）神经元的细胞体环，称为桶，对应于面部胡须。为了正确地形成桶，它需要L4神经元的特化和来自晶须的突触输入活动。神经元如何对神经元活动作出反应以形成桶在很大程度上是未知的。此外，桶皮质在早期发育阶段表现出显着的可塑性。桶状皮质的可塑性是如何被基因调控的仍然是个谜。Chou博士的实验室已经确定了Lhx2在有丝分裂后神经元调节桶皮质发育中的新作用，而Luhmann博士一直在研究出生后第一周桶皮质中神经元活动的变化。最近，我们发现Lhx2突变小鼠的桶状皮质可塑性受损。在这个提议中，我们计划比较野生型（WT）和Lhx2突变动物在出生后第一周桶皮质可塑性发育过程中神经元活动的变化。结合周博士的小组在小鼠遗传学和皮层发育方面的专业知识和Luhmann博士的小组在新生小鼠体内电生理记录和新皮层成像和数据分析方面的专业知识，我们建议研究Lhx2在建立桶皮层可塑性过程中调节结构和功能变化的机制。

Cortical neurons form synaptic circuits to accomplish the intricate functions of the cerebral cortex. Circuit formation during early development involves the interplay of intrinsic genetic programs regulated by transcription factors and extrinsic activity-dependent processes from synaptic inputs. To identify the function of transcription factors on regulating changes in activity-dependent neuronal properties, we propose here to use the rodent barrel cortex as a model to investigate the function of Lhx2, a LIM homeodomain transcription factor, in regulating barrel cortex plasticity. The barrel cortex in the primary somatosensory cortex (S1) in mouse brain is an ideal system to study the formation of cortical circuitry. The barrel cortex is topographically organized into rings of cell bodies of layer 4 (L4) neurons, called barrels, corresponding to the facial whiskers. To form barrels properly, it requires the specification of L4 neurons and the synaptic input activity from the whiskers. How neurons respond to neuronal activity to form barrels is largely unknown. Further, the barrel cortex shows a remarkable plasticity during early developmental stages. How the barrel cortex plasticity is genetically regulated remains elusive. Dr. Chou’s lab had identified a novel role of Lhx2 in postmitotic neurons regulating barrel cortex development, while Dr. Luhmann has been studying the changes of neuronal activities in barrel cortex during the first postnatal weeks. Recently, we found in Lhx2 mutant mice, the barrel cortex plasticity is impaired. In this proposal, we plan to compare the changes of neuronal activities in wild type (WT) and Lhx2 mutant animals during barrel cortex plasticity development in the first postnatal week. Combining the expertise of Dr. Chou’s group in mouse genetics and cortical development and Dr. Luhmann’s group in in vivo electrophysiological recordings and neocortical imaging in neonatal mice and data analysis, we propose to investigate the mechanisms for Lhx2 to regulate the structural and functional changes during the establishment of barrel cortex plasticity.