Hippocampal synaptic dynamics during realistic patterns of afferent activity

描述(申请人提供)：突触传递是神经系统细胞间信号传递和处理的主要机制。突触的输出是高度动态的，这是因为存在几种形式的依赖活动的突触可塑性，持续时间从毫秒到几个小时不等。尽管突触可塑性的个体形式已经被很好地描述，但用于定义每种形式可塑性的简单刺激模式与体内看到的活动模式几乎没有相似之处，在活体中，大多数突触是由时间上复杂的传入放电模式激活的。这些复杂的活动模式预计会在复杂的组合中同时进行几种形式的突触可塑性，我们将称之为突触动力学。突触动力学决定了每个棘波产生的突触输出如何受到前一个棘波序列模式的影响。这些动力学被广泛认为是突触传递过程中信号处理的重要组成部分，并可能受到药物或神经系统疾病的影响；然而，在真实的传入活动模式中，突触动力学却知之甚少。我们的长期目标是确定突触动力学在海马体电路功能中的作用，海马体是学习和记忆的关键大脑结构。在目前的建议中，我们将研究海马片中CA3锥体细胞和CA1锥体细胞之间Schaffer侧支突触的突触动力学。我们将使用现场和全细胞记录来测量在执行复杂行为任务期间，从体内CA3锥体细胞的活动模式中获得的对棘波序列的突触反应。我们将解决三个具体目标：1)确定与行为相关的传入活动模式中突触动力学的功能后果；2)确定突触动力学背后的机制；3)确定神经调节剂或长期可塑性是否可以改变突触动力学。

DESCRIPTION (provided by applicant): Synaptic transmission is a major mechanism underlying the intercellular transfer and processing of signals in the nervous system. The output of synapses is highly dynamic, owing to the existence of several forms of activity-dependent synaptic plasticity that range in duration from milliseconds to hours. Although individual forms of synaptic plasticity have been well described, the simple stimulus patterns used to define each form of plasticity bear little resemblance to the activity patterns seen in vivo, where most synapses are activated by temporally complex patterns of afferent firing. These complex patterns of activity are expected to engage several forms of synaptic plasticity simultaneously in a complex combination, which we will refer to as synaptic dynamics. Synaptic dynamics determine how the synaptic output produced by each spike is influenced by the pattern of the preceding spike train. These dynamics are widely presumed to be an important component of signal processing during synaptic transmission, and may be affected by drugs or neurological diseases; however, synaptic dynamics during realistic patterns of afferent activity are poorly understood. Our long-term objective is to determine the roles of synaptic dynamics in circuit function in the hippocampus, a brain structure critical in learning and memory. In the present proposal, we will examine synaptic dynamics of Schaffer collateral synapses between CA3 pyramidal cells and CA1 pyramidal cells in hippocampal slices. We will use field and whole-cell recordings to measure synaptic responses to spike trains derived from activity patterns seen in CA3 pyramidal cells in vivo during the performance of a complex behavioral task. We will address three specific aims: 1) to identify functional consequences of synaptic dynamics during behaviorally-relevant patterns of afferent activity; 2) to identify mechanisms that underlie synaptic dynamics; and 3) to determine whether synaptic dynamics can be altered by neuromodulators or long-term plasticity.