Developmental Changes in Excitatory Synapses in Hippocampus

描述（由申请人提供）：内嗅皮层和海马体对学习和记忆都至关重要。内嗅皮层与几种神经系统疾病有关，包括导致智力迟钝的发育障碍。从内嗅皮层到海马的一个主要输入通路是海马CA1区的颞氨（TA）通路。TA通路向CA1提供特定的感觉信息，并已被证明与记忆巩固有关。由于TA通路对学习和记忆的重要性，TA突触功能特性的改变可能导致发育障碍患者的认知障碍。这种变化可能在形态学水平上不明显，但需要电生理学检测。研究人员的长期目标是利用电生理学来寻找发育障碍动物模型中突触和回路功能的变化。为了为这项研究奠定基础，他们将首先调查正常发育过程中突触功能的变化。他们之前已经表明，在出生后早期发育过程中，CA1的另一个主要输入通路，Schaffer侧枝通路（SC）突触的突触前功能发生了变化。为了了解这些发育变化对海马功能的影响，研究人员还需要了解TA突触的特性以及它们在发育过程中是如何被调节的。相对而言，人们对TA突触的突触前功能以及它们与SC突触的比较知之甚少，而且对于TA突触的特性是否也受到发育调节也一无所知。由于TA和SC突触都影响海马主要输出神经元CA1神经元的放电，因此它们的动态特性是正常海马功能和海马回路发育的关键决定因素。在这项小型拨款申请中，研究人员将使用大鼠的海马脑切片作为模型系统，并使用电生理学来测量青少年和年轻成人的TA突触切片的突触前特性。他们将验证以下假设：突触前特性的发育调节在TA突触和SC突触之间是根本不同的，以及在幼体和年轻成虫中TA突触和SC突触之间的短期可塑性是不同的。了解影响CA1细胞放电的不同输入通路的发育变化，对于了解正常新生儿发育过程中海马回路功能的变化非常重要。总之，本研究为进一步研究海马突触和回路的功能特性和发育调节提供了基础，这些突触和回路可能在导致智力迟钝的发育障碍动物模型中导致认知障碍。

DESCRIPTION (provided by applicant): The entorhinal cortex and hippocampus are both critical for learning and memory. The entorhinal cortex has been implicated in several neurological diseases, including developmental disorders that cause mental retardation. One major input pathway from entorhinal cortex to hippocampus is the temporoammonic (TA) pathway to the CA1 region of hippocampus. The TA pathway provides specific sensory information to CA1, and it has been shown to be involved in memory consolidation. Because of the importance of the TA pathway to learning and memory, alterations in the functional properties of TA synapses could contribute to cognitive impairment in developmental disorders. Such changes might not be apparent at the morphological level, but would require electrophysiology to be detected. The investigators' long term objective is to use electrophysiology to look for changes in the function of synapses and circuits in animal models of developmental disorders. To lay the foundation for that research they will first investigating the changes in synaptic function that occur during normal development. They have previously shown changes during early postnatal development in presynaptic function of synapses in the other major input pathway to CA1, the Schaffer collateral (SC) pathway. In order to understand the impact of these developmental changes for hippocampal function, the investigators also need to know the properties of TA synapses and how they are modulated during development. Relatively little is known about the presynaptic function of TA synapses and how they compare to SC synapses, and nothing is known about whether the properties of TA synapses are also developmentally regulated. Because both TA and SC synapses influence the firing of CA1 neurons, the main output neurons of hippocampus, their dynamic properties are crucial determinants of normal hippocampal function and development of hippocampal circuitry. In this small grant application, the investigators will use hippocampal brain slices from rats as a model system, and use electrophysiology to measure the presynaptic properties of TA synapses in slices from juveniles versus young adults. They will test the hypothesis that developmental modulation of presynaptic properties is fundamentally different between TA synapses and SC synapses, and that short-term plasticity is different between TA synapses and SC synapses in both juveniles and young adults. Understanding the developmental changes in the different input pathways that influence CA1 cell firing will be important for understanding how the function of the hippocampal circuit changes during normal neonatal development. Together, this research provides the foundation for future studies on the functional properties and developmental modulation of hippocampal synapses and circuits that could contribute to cognitive impairment in animal models of developmental disorders that cause mental retardation.