COBRE: TU: PROJ 2: MECHANISMS OF ACETYLCHOLINE PLASTICITY IN HYPOTHALAMUS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。谷氨酸和γ-氨基丁酸(GABA)是中枢神经系统(CNS)包括下丘脑在内的大多数区域的两种主要的快速神经递质(兴奋性和抑制性)。它们共同在控制神经元的活性和兴奋性方面起着关键作用，并决定了许多神经元回路中突触的兴奋/抑制平衡。在癫痫、阿尔茨海默病、缺血和心跳停止期间，人类海马区和大脑皮层中含有谷氨酸的投射神经元发生选择性变性。我们以前的实验表明，慢性阻断离子型谷氨酸受体显著增加大鼠下丘脑神经元培养中乙酰胆碱(ACh)神经传递的表达。谷氨酸兴奋减弱后ACh活性的升高与ACh受体的上调有关。这证明了NMDA谷氨酸受体阻断(但不是非NMDA受体阻断或活性依赖机制)在胆碱能活动诱导中的重要作用。此外，数据表明，在下丘脑培养中没有谷氨酸兴奋的情况下，另一种兴奋性神经递质Ach支持兴奋/抑制平衡。因此，我们推测，在下丘脑神经元培养中谷氨酸兴奋的长期下降过程中，正常情况下在下丘脑表现出较弱活动的Ach开始发挥主要兴奋性神经递质的作用，并支持兴奋/抑制平衡。我们还假设，在没有谷氨酸兴奋的情况下，兴奋性ACh传递的增加是神经元可塑性的一种形式，在谷氨酸/GABA失衡期间调节神经元的活性和兴奋性。在我们未来的研究中，我们将探讨在没有谷氨酸刺激的情况下，钙离子依赖于谷氨酸调节ACh传递的机制是神经元可塑性的一种形式，在谷氨酸/GABA失衡期间调节神经元的活性和兴奋性。在我们未来的研究中，我们将在体外研究钙离子对谷氨酸依赖的下丘脑ACh传递的调节机制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Glutamate and gamma-aminobutyric acid (GABA) are two major fast neurotransmitters (excitatory and inhibitory, respectively) in most regions of the central nervous system (CNS), including the hypothalamus. Together, they play a key role in the control of the activity and excitability of neurons and determine the synaptic excitation/inhibition balance in many neuronal circuits. Selective degeneration of glutamate-containing projecting neurons occurs in the human hippocampus and cerebral cortex during epilepsy, Alzheimer's disease, ischemia, and cardiorespiratory arrest. Our previous experiments revealed that a chronic blockade of ionotropic glutamate receptors dramatically increased the expression of acetylcholine (ACh) neurotransmission in rat hypothalamic neuronal cultures. The increase in ACh activity following the decrease in glutamate excitation was associated with the up-regulation of ACh receptors. This demonstrates the important role of NMDA glutamate receptor blockade (but not non-NMDA receptor blockade or activity-dependent mechanisms) for the induction of cholinergic activity. Additionally, the data suggest that in the absence of glutamate excitation in hypothalamic cultures, Ach, another excitatory neurotransmitter, supports the excitation/inhibition balance. We therefore postulate that during a long-term decrease in the glutamate excitation in hypothalamic neuronal cultures, Ach, which normally exhibits a weak activity in the hypothalamus, begins to play the role of the major excitatory neurotransmitter and to support the excitation/inhibition balance. We also hypothesize that the increase in excitatory ACh transmission in the absence of glutamate excitation is a form of neuronal plasticity that regulates the activity and excitability of neurons during the glutamate/GABA imbalance. In our future research, we will address Ca2+ mechanisms of glutamate-dependent regulation of ACh transmission in the absence of glutamate excitation is a form of neuronal plasticity that regulates the activity and excitability of neurons during the glutamate/GABA imbalance. In our future research, we will address Ca2+ mechanisms of glutamate-dependent regulation of ACh transmission in the hypothalamus in vitro.