Regulation of Barrel Cortex Plasticity

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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.