Project title to be confirmed on completion of the training period.

“目前对皮质-丘脑-皮层（CTC）网络如何产生振荡的理解是相当充分的，这种振荡是在睡眠和轻度麻醉期间观察到的。然而，这些振荡是如何内源性调节的，并在致病性状态下（如癫痫缺失）如何变得失调，还没有完全确定。最近的研究表明，神经调节剂腺苷在控制CTC振荡中起关键作用，腺苷可作用于A1受体以降低神经元活性。腺苷A1受体在丘脑基底腹侧和丘脑网状核中密集表达，并在激活后减少/消除振荡。相反，用拮抗剂阻断A1受体可增强振荡，因此内源性腺苷与A1受体结合代表了振荡控制的内源性反馈机制（Wall等，2022）。本研究的主要目的是使用新的药理化合物来解剖腺苷对CTC网络的影响。BNOCPA是一种新型A1受体激动剂，在G蛋白之间表现出显著的选择性，仅激活Golb亚型（Wall et al., 2022）。这种独特的性质将使研究腺苷调节振荡的确切机制成为可能，并允许在电路中绘制G蛋白表达图。BNOCPA的衍生物具有不同的效力和选择性，并将在CTC电路中进行测试。

"The current understanding of how the cortico-thalamic-cortical (CTC) network generates oscillations, which are observed during sleep and light anaesthesia is reasonably well understood. However, how these oscillations are endogenously modulated and can become dysregulated in pathogenic states, such as absence epilepsy, has not been fully determined. Recent studies have shown that the neuromodulator adenosine, which acts at A1 receptors to reduce neuronal activity, plays a key role in controlling CTC oscillations. Adenosine A1 receptors are densely expressed in the ventral basal thalamus and the reticular thalamic nucleus and reduce/abolish oscillations upon activation. In contrast, blocking A1 receptors, with an antagonist enhances oscillations and thus endogenous adenosine binding to A1 receptors represents an endogenous feedback mechanism for oscillation control (Wall et al., 2022).A primary aim of this study is to use novel pharmacological compounds to dissect apart the effects of adenosine on the CTC network. BNOCPA is a novel A1 receptor agonist which shows remarkable selectivity between G proteins, only activating the Golb isoform (Wall et al., 2022). This unique property will enable study of the exact mechanisms by which adenosine regulates oscillations and allow mapping of G protein expression within the circuit. Derivatives of BNOCPA, with different potencies and selectivity's have been developed and will be tested in the CTC circuit."