Developmental Changes in Excitatory Synapses in Hippocampus

描述(申请人提供)：内嗅皮层和海马体对学习和记忆都很重要。内嗅觉皮质与几种神经疾病有关，包括导致智力低下的发育障碍。从内嗅觉皮质到海马区的一条主要输入通路是到海马区CA1区的颞氨(TA)通路。TA通路为CA1提供特定的感觉信息，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中的认知障碍。这样的变化在形态层面上可能不明显，但需要检测到电生理学。研究人员的长期目标是利用电生理学在发育障碍的动物模型中寻找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。在出生后早期，它们已经显示出CA1的另一条主要输入通路--Schaffer侧支(SC)通路中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体功能的影响，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调节的。关于TA突触的突触前功能以及它们与SC突触的比较，人们知之甚少，也不知道TA突触的特性是否也受到发育调控。由于TA和SC突触都影响CA1神经元的放电，CA1神经元是海马区的主要输出神经元，因此它们的动力学特性是决定海马正常功能和海马回路发育的关键因素。在这项小额拨款申请中，研究人员将使用大鼠的海马脑片作为模型系统，并使用电生理学来测量青少年和年轻人脑片中TA突触的突触前特性。他们将测试这样一个假设，即TA突触和SC突触之间对突触前特性的发育调节是根本不同的，而且在青少年和年轻人中，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，对于理解正常新生儿发育过程中海马区回路的功能变化具有重要意义。总之，这项研究为未来研究海马区突触和回路的功能特性和发育调节奠定了基础，这些突触和回路可能导致导致智力低下的发育障碍动物模型的认知障碍。

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.