Modulation of Entorhinal Cortex Neurons by Adenosine and Implications in TLE

腺苷对内嗅皮层神经元的调节及其对 TLE 的影响

• 批准号: 8050088
• 负责人: Nicholas Hargus
• 金额: $ 0.53万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8050088
• 关键词: Action Potentials; Adenosine; Adult; Affect; American; Anticonvulsants; Area; Brain; Complex; Data; Diagnosis; Epilepsy; Generations; Hippocampus (Brain); Human; Immunohistochemistry; In Situ Hybridization; Intervention; Lead; Mediating; Medical; Modeling; Molecular Profiling; Neurons; Output; Pathology; Patients; Pattern; Physiological; Play; Population; Property; Purinergic P1 Receptors; Rattus; Refractory; Reporting; Research; Role; Seizures; Slice; Structure; Synaptic Transmission; Temporal Lobe; Temporal Lobe Epilepsy; Testing; Tissues; entorhinal cortex; nervous system disorder; neuronal excitability; novel; research study

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.

假设腺苷在调节内嗅皮层（EC）II层神经元兴奋性中起关键作用，并且将通过腺苷对癫痫组织的兴奋性调节更大，将在我们的脑切片中测试，也将从我们的对照大鼠中获得的脑切片中的大脑片，以及我们的大鼠epilepsy（Tle）的大鼠模型（TLE）。提出的实验将研究腺苷在对照和癫痫病中调节EC II层神经元中内在和突触驱动的动作电位发射的能力，并研究通过两个特定目的介导这种差异调节的机制：1。测试腺苷介导的腺苷介导的内在启动和突触的ec型Neur in Is ii IS ii IIS Neur int ii IS ii IS ii IS的模型。 2。检验以下假设：在我们的大鼠TLE大鼠模型中，EC II层神经元中腺苷受体亚型表达模式发生了变化。初步数据表明，与对照切片相比，在我们的大鼠TLE模型中，EC II层神经元可过度兴奋。数据还表明，腺苷能够抑制来自对照组织的EC II层神经元中的内在和突触驱动的动作电位发射，并且在调节对照组织中EC II层II神经元无效的腺苷浓度足以抑制我们从tle的Rat Rat Mode of Tle的EC II层II神经元中的EC II层发射。电生理记录将用于检查这些神经元的发射特性以及腺苷应用对这些神经元兴奋性的影响，并比较控制和TLE条件之间的作用。在两种情况下，将进行原位杂交和免疫组织化学实验，以检查EC中EC中腺苷受体亚型的表达谱和水平，以确定差异调制的机制。