Thalamocortical Boundary Markers and the Influence of Serotonin

大脑皮质的发育受内在和外在因素的调节，包括引导分子。 和神经递质，这些物质可能会受到药物或其他环境因素的影响。以弗 受体是受体酪氨酸激酶家族的成员，它与配体蛋白相互作用， 肾上腺素，调节大脑结构的模式，特别是从丘脑投射到 皮质，丘脑皮质传入(TCAs)。这些分子是很好的候选者 出生后边界的形成以及可能在纠正TCA模式中引起的错误方面。我们以前的 结果表明，新生大鼠TCA模式被过量的纤维生长所破坏 递质5-羟色胺(5-羟色胺)水平，但这些模式在第二个过程中变得正常 出生后一周，尽管5-羟色胺持续升高。此外，TCA的增长也有空间限制。 5-羟色胺诱导。限制异常生长和移除轴突的过程的边界的存在 从不适当的区域可能取决于排斥的分子相互作用和Eph/ePhin的表达 家族分子与它们参与其中一种或两种机制是一致的。的目标是 拟开展的研究旨在探讨Ephs/Ephins在皮质边界形成和表达中的作用。 为了测试这些分子是否在TCA模式受到干扰时重新定向轴突以使其正常化， 例如，改变皮质5-羟色胺水平的药物(苯丙胺，SSRIs)。具体目标是： 1.检测Eph/Ephin蛋白和mRNA在体内及周围的分布 躯体感觉皮层(S-L)和丘脑腹基底核(VB)。这些基因的表达模式 分子将通过免疫组织化学和原位杂交进行可视化。 2.研究Eph/Ephin分子对个体TCA模式和乔木的影响 TCA轴突。使用功能得失实验来测试TCA是否受 伊夫林分布的局部变化.. 3.确定Eph/ePhin分子在使融合的TCA模式正常化中的作用 由皮质5-羟色胺水平升高引起。Eph/ePhin分布和功能的变化 将调查图案归一化的周期。 通过这些研究获得的知识将扩大我们对一类内源性 引导线索有助于确定皮质边界，并参与由 对广泛使用的药剂敏感的皮质递质的改变。

Development of the cortex is regulated by both intrinsic and extrinsic factors, including guidance molecules and neurotransmitters, that may be impacted by pharmacological or other environmental agents. The Eph receptors are members of the family of receptor tyrosine kinases which interact with ligand proteins, the ephrins, to mediate patterning of brain structures, in particular the axons that project from the thalamus to cortex, the thalamocortical afferents (TCAs). These molecules are good candidates for involvement in postnatal boundary formation and possibly in correcting errors induced in TCA patterns. Our previous results showed that TCA patterns are disrupted by excessive fiber outgrowth in neonate rats by elevated levels of the transmitter serotonin (5-HT), and yet these patterns become normalized during the second postnatal week, despite continued elevation of 5-HT. Moreover, there are spatial limits to TCA outgrowth induced by 5-HT. The existence of boundaries limiting abnormal growth and processes that remove axons from inappropriate regions may depend on repulsive molecular interactions, and expression of Eph/ephrin family molecules are consistent with their involvement with either or both of these mechanisms. The goal of the proposed research is to investigate the potential role of Ephs/ephrins in cortical boundary formation and to test whether these molecules redirect axons to normalize TCA patterns when these are perturbed, for example by drugs that alter cortical 5-HT levels (amphetamines, SSRIs). The specific aims are: 1. Examine the distribution of Eph/ephrin protein and mRNA in and surrounding somatosensory cortex (S-l) and ventrobasal thalamus (VB). Expression patterns of these molecules will be visualized by immunohistochemistry and in situ hybridization. 2. Examine the influence of Eph/ephrin molecules on TCA patterns and arbors of individual TCA axons. Gain and loss of function experiments are used to test to test if TCAs are influenced by local changes in ephrin distributions.. 3. Determine the role of Eph/ephrin molecules in normalizing fused TCA patterns resultant from elevation of cortical 5-HT levels. Changes in Eph/ephrin distributions and function during the period of pattern normalization will be investigated. The knowledge gained by these studies will expand our understanding of how one class of endogenous guidance cues helps to define cortical boundaries and participates in early brain plasticity induced by the alteration of a cortical transmitter which is susceptible to widely utilized pharmaceutical agents..