Effects of Ethanol on Hippocampal Synaptic Plasticity

神经发育过程中的乙醇暴露会对大脑功能产生长期的不良影响，导致记忆缺陷和患重大精神疾病的高风险。 神经精神功能变化的机制尚不清楚，但认为是由于对突触传递的影响。 最近，Olney及其同事提供了关于乙醇对发育中的中枢神经系统（CNS）影响的重要信息。 这些研究人员发现，在出生后的早期大鼠中，在单一的4小时内用致醉剂量的乙醇治疗，导致CNS的许多区域（包括海马）发生大量的凋亡性神经变性。 由于海马体在记忆处理中起着关键作用，因此该结构的早期损伤可能会影响长期记忆功能。 在这项建议中，我们将研究的后果，早期出生后乙醇暴露突触功能和可塑性使用体外海马切片制备的青少年和年轻的成年大鼠暴露于乙醇的年龄与增强海马细胞凋亡。 该项目的具体目标是：1。目的：研究生后早期乙醇暴露对海马脑片CA 1区基础突触传递、N-甲基-D-天冬氨酸谷氨酸受体（NMDARs）介导的突触反应以及NMDARs依赖的长时程增强（LTP）和长时程突触抑制（LTD）的影响。 对于这些研究，我们将使用从出生后第35天（P35）和P180大鼠制备的切片。 2.确定在出生后发育早期暴露于乙醇的青少年（P35）和成年（P180）大鼠海马形态和可塑性的变化如何转化为海马依赖性学习和记忆形式的变化。 这些研究将建立在初步的数据表明，早期乙醇暴露的结果在CA 1海马区诱导同突触LTD的能力显着变化。 希望更好地了解出生后早期乙醇暴露如何改变海马功能，将导致更有效的治疗胎儿酒精暴露引起的疾病的个体。

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.