Behavioral and physiological profiling of developmental critical periods

大脑在适当的时间和地点的可塑性在发育过程中至关重要，并在整个生命中产生持久的影响。就像早期的感觉输入塑造了初级感觉皮层一样，情感体验也可能塑造了边缘皮层中继系统。在断奶后期间，来自BLA的纤维在mPFC内活跃地发芽，与GABA能中间神经元形成增加的接触，直到成年早期。这种连接需要进一步的超微结构评价（与Lichtman），并在这些并置的受体的身份值得调查（与Zhuang）。在这里，我们专注于神经回路机制的转变，从杏仁核到mPFC潜在的恐惧灭绝整个发展。使用这些阶段作为一个里程碑，我们将测量开发突触输入到单个PV细胞的mPFC的全细胞记录技术在切片从PV-EGFP小鼠杂交到各种小鼠模型。特别是来自BLA的传入神经的成熟状态将通过该投射的光遗传学标记来检查。最终，我们的目标是确定是否动态表观遗传调控（如由迪拉克识别的印记基因）决定这些关键的皮层抑制回路的功能成熟。确定细胞特异性机制，表观遗传调控的关键时期可能提供有价值的洞察潜在的电路为基础的治疗所产生的异常环境-基因相互作用的病理。

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.