Effects of Ethanol on Hippocampal Synaptic Plasticity

乙醇对海马突触可塑性的影响

• 批准号: 6797413
• 负责人: CHARLES F ZORUMSKI
• 金额: $ 22.14万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6797413
• 关键词: NMDA receptors; alcoholism /alcohol abuse; apoptosis; ethanol; hippocampus; laboratory rat; learning; long term potentiation; memory; neural inhibition; neural plasticity; neuropharmacology; receptor expression; synapses

Ethanol exposure during neurodevelopment can have long- term adverse effects on brain function, resulting in defects in memory and a high risk for major psychiatric disorders. The mechanisms underlying the changes in neuropsychiatric function are poorly understood but thought to result from effects on synaptic transmission. Recently, Olney and colleagues provided important information about the effects of ethanol on the developing central nervous system (CNS). These investigators found that treatment of early postnatal rats with intoxicating doses of ethanol over a single four hour period results in massive apoptotic neurodegeneration in many regions of the CNS, including the hippocampus. Because the hippocampus plays a key role in memory processing, it is likely that early damage to this structure influences longer-term memory function. In this proposal, we will examine the consequences of early postnatal ethanol exposure on synaptic function and plasticity using in vitro hippocampal slices prepared from adolescent and young adult rats exposed to ethanol at ages associated with augmented hippocampal apoptosis. The specific aims of this project are: 1. To determine the effects of early postnatal ethanol exposure on basal synaptic transmission, synaptic responses mediated by N- methyl-D-aspartate glutamate receptors (NMDARs) and the threshold for induction of NMDAR-dependent long-term potentiation (LTP) and long-term synaptic depression (LTD) in the CA1 region of hippocampal slices. For these studies we will use slices prepared from postnatal day 35 (P35) and P180 rats. 2. To determine how changes in hippocampal morphology and plasticity translate into changes in hippocampal-dependent forms of learning and memory in adolescent (P35) and adult (P180) rats exposed to ethanol early in postnatal development. These studies will build on preliminary data indicating that early ethanol exposure results in significant changes in the ability to induce homosynaptic LTD in the CA1 hippocampal region. It is hoped that better understanding of how early postnatal ethanol exposure alters hippocampal function will lead to more effective treatments for individuals with disorders resulting from fetal alcohol exposure.

神经发育过程中的乙醇暴露会对脑功能产生长期不良影响，从而导致记忆缺陷和严重精神疾病的高风险。 神经精神功能变化的机制知之甚少，但认为是由于对突触传播的影响而产生的。 最近，奥尔尼（Olney）及其同事提供了有关乙醇对发展中枢神经系统（CNS）的影响的重要信息。 这些研究者发现，在一个四小时的时间内对早期的产后大鼠进行醉酒剂量的乙醇的治疗导致中枢神经系统（包括海马）的许多区域都大量凋亡神经变性。 由于海马在记忆过程中起关键作用，因此对这种结构的早期损害可能会影响长期内存功能。 在此提案中，我们将使用体外海马乙醇对突触功能和可塑性的后果，使用与增强海马凋亡相关的年龄相关的青少年和成年大鼠制备的体外海马切片。 该项目的具体目的是：1。确定早期产后乙醇暴露对基底突触传播的影响，由N-甲基-D-天冬氨酸谷氨酸谷氨酸受体（NMDARS）介导的突触反应以及NMDAR依赖性长期强度（LTP）诱导阈值的阈值（LTP）和长期的长期突触抑制（LTD）。 对于这些研究，我们将使用从产后第35天（P35）和P180大鼠制备的切片。 2。为了确定海马形态和可塑性的变化如何转化为青少年（p35）（p35）和成年（p180）大鼠海马依赖形式的学习和记忆形式的变化。 这些研究将基于初步数据，表明早期的乙醇暴露会导致诱导CA1海马区域中诱导同伴有限公司的能力发生重大变化。 希望更好地了解早期产后乙醇暴露如何改变海马功能将为胎儿酒精暴露导致的疾病患者提供更有效的治疗方法。