Developmental changes in presynaptic function

出生后的发育在大脑突触传递方面产生了深刻的变化。许多发育研究都集中在通过突触连接的巩固或消除来改变神经元之间的连接。然而，对突触强度的发育调节知之甚少，突触强度也可能在正常的新生儿发育中发挥关键作用。这种调节可能发生在突触前，或两者同时发生。虽然有一些研究关注突触后特性的发育变化，但很少关注突触前功能的发育变化。这是一个重要的领域，因为大量证据表明突触前机制参与了几种突触可塑性的分子实现和维持，这些可塑性是学习和记忆的基础，受到各种形式的智力迟钝的损害。因此，本研究的目的是研究在新生儿发育过程中，大脑皮层兴奋性突触突触前功能的变化所起的作用。这种方法的一个独特方面是应用行为显著，自然的激活时间模式来测试新生儿突触的动态特征。本文描述了一系列的实验来确定新生儿海马突触前功能的发育调节。利用电生理和药理学技术，在出生后的前五周内评估突触释放概率、短期可塑性和功能连通性的发育变化。了解突触前特性的正常发育是研究产前和产后环境因素（如母亲营养不良导致短期记忆认知缺陷）影响的必要的第一步。由于短期可塑性可能是短期记忆的细胞基质，了解短期可塑性的正常发育特性是确定短期可塑性和短期记忆在这些不同综合征中如何受损的关键先决条件。

Postnatal development produces profound changes in synaptic transmission in the brain. Many developmental studies have focused on changes in the connections between neurons through consolidation or elimination of synaptic connection. Much less is known, however, about the developmental modulation of the strength of synapses, which is also likely to play a critical role in normal neonatal development. This modulation could occur pre-synaptically, or both While several studies have looked at developmental changes in postsynaptic properties, little attention has been paid to developmental changes in presynaptic function. This is an important area since considerable evidence suggests that presynaptic mechanisms are involved in the molecular implementation and maintenance of several types of synaptic plasticity implicated as substrates for learning and memory that are subject to impairment in various forms of mental retardation. Thus, the goal of this proposal is to examine the role of changes in presynaptic function at cerebral cortical excitatory synapses, that utilize the neurotransmitter glutamate, during neonatal development. A unique aspect of this approach is the application of behaviorally salient, natural temporal patterns of activation for testing the dynamic features of neonatal synapses. This proposal describes a series of experiments to determine the developmental regulation of presynaptic function in neonatal hippocampus. Using electrophysiological and pharmacological techniques, developmental changes in synaptic release probability, short- term plasticity, and functional connectivity will be assessed during the first five postnatal weeks. Understanding the normal development of presynaptic properties is a necessary first step to investigating the effects of pre- and postnatal environmental factors, such as maternal malnutrition cause cognitive deficits in short-term memory. Since short-term plasticity is likely to be a cellular substrate for short-term memory, understanding the normal developmental properties of short-term plasticity is a key prerequisite to determining how short-term plasticity and short-term memory are impaired in these different syndromes.