Behavioral and physiological profiling of developmental critical periods

在正确的时间和地点，大脑的可塑性在发育过程中至关重要，并对整个生命产生持久的影响。正如生命早期的感觉输入会塑造初级感觉皮层一样，情绪体验可能会塑造边缘-皮层中继系统。在断奶后的时期，来自BLA的纤维在mPFC内积极发芽，直到成年早期才与gaba能中间神经元形成更多的接触。这种连通性需要进一步的超微结构评估（与Lichtman），而这些受体的身份值得研究（与庄）。在这里，我们将重点放在从杏仁核到mPFC的神经回路机制的转变上，这是整个发育过程中恐惧消退的基础。以这些阶段为里程碑，我们将通过将PV-EGFP小鼠的切片与各种小鼠模型杂交，采用全细胞记录技术来测量mPFC中单个pv细胞的突触输入。特别是来自BLA的事件的成熟状态，将通过该投影的光遗传标记进行检查。最终，我们的目标是确定动态表观遗传调控（如由Dulac鉴定的印迹基因）是否决定了这些关键皮层抑制回路的功能成熟。识别关键时期表观遗传调控的细胞特异性机制可能为潜在的基于回路的疗法提供有价值的见解，以治疗由异常环境-基因相互作用引起的病理。

Brain plasticity at the right time and place is of paramount importance during development with lasting consequence throughout life. Just as sensory input in early life shapes primary sensory cortex, emotional experience may shape the limbic-cortical relay system. Fibers from the BLA actively sprout within the mPFC during the post-weanling period, forming increased contacts with GABAergic interneurons as late as the early adult period. This connectivity requires further evaluation ultrastructurally (with Lichtman), and the identity of the receptors at these appositions merits investigation (with Zhuang). Here, we focus on the shift of neural circuit mechanisms from amygdala to mPFC underlying fear extinction across development. Using these stages as a milestone, we will measure developing synaptic inputs onto individual PV-cells of the mPFC by whole-cell recording techniques in slices from PV-EGFP mice crossed to various mouse models. The maturational state of afferents from the BLA in particular, will be examined by optogenetic tagging of this projection. Ultimately, we aim to determine whether dynamic epigenetic regulation (such as by imprinted genes identified by Dulac) dictates the functional maturation of these pivotal cortical inhibitory circuits. Identifying cell-specific mechanisms that underlie epigenetic regulation of critical periods may provide valuable insight into potential circuit-based therapies for pathologies arising from aberrant environment-gene interactions.