Modulation of Entorhinal Cortex Neurons by Adenosine and Implications in TLE

腺苷在调节内鼻皮层（EC）第二层神经元兴奋性中起关键作用的假设，以及腺苷对癫痫组织的兴奋性有更大的调节作用的假设，将在从对照大鼠和我们的颞叶癫痫（TLE）大鼠模型中获得的脑切片中进行验证。本实验将研究腺苷在控制和癫痫状态下调节EC II层神经元内在和突触驱动的动作电位放电的能力，并通过两个特定目的研究介导这种差异调节的机制：1。在我们的大鼠TLE模型中验证腺苷介导的内源性和突触驱动的EC II神经元动作电位放电的调节被改变的假设。2. 在我们的大鼠TLE模型中验证EC II层神经元中腺苷受体亚型表达模式改变的假设。初步数据表明，与对照切片相比，我们的大鼠TLE模型中的EC层II神经元是过度兴奋的。数据还显示，腺苷能够抑制来自对照组织的EC II层神经元的内在和突触驱动的动作电位放电，并且在对照组织中对EC II层神经元无效的腺苷浓度足以抑制大鼠TLE模型中EC II层神经元的动作电位放电。电生理记录将用于检查这些神经元的放电特性和腺苷应用对这些神经元兴奋性的影响，比较对照和TLE条件下的行为。将进行原位杂交和免疫组织化学实验，以检查两种情况下EC中腺苷受体亚型的表达谱和水平，以确定差异调节的机制。

The hypothesis that adenosine plays a key role in modulating entorhinal cortex (EC) layer II neuronal excitability and that there is a greater modulation of excitability in epileptic tissue by adenosine will be tested in brain slices obtained from control rats as well from our rat model of temporal lobe epilepsy (TLE). The proposed experiments will study adenosine's ability to modulate both intrinsic and synaptically driven action potential firing in EC layer II neurons in the control and epileptic condition and investigate the mechanisms that mediate this differential modulation through two specific aims: 1. Test the hypothesis that adenosine mediated modulation of intrinsic and synaptically driven action potential firing of EC layer II neurons is altered in our rat model of TLE. 2. Test the hypothesis that adenosine receptor subtype expression patterns are altered in EC layer II neurons in our rat model of TLE. Preliminary data suggest that EC layer II neurons are hyperexcitable in our rat model of TLE as compared to control slices. Data also reveals that adenosine is able to inhibit both intrinsic and synaptically driven action potential firing in EC layer II neurons from control tissue and that concentrations of adenosine that are ineffective in modulating EC layer II neurons in control tissue are sufficient to inhibit action potential firing in EC layer II neurons from our rat model of TLE. Electrophysiological recordings will be used to examine the firing properties of these neurons and the effect that adenosine application has on the excitability of these neurons, comparing the actions between the control and TLE conditions. In situ hybridization and immunohistochemistry experiments will be carried out in order to examine the expression profile and levels of adenosine receptor subtypes in the EC in both conditions to determine the mechanism underlying the differential modulation.