Plasticity of Oxytocin Neurons During Lactation

描述（申请人摘要）：神经分泌神经元有一个大的 形态和生理可塑性的能力， 成年期的内分泌状态。该项目的主要利益是 视上核和室旁核新突触的形成 下丘脑-神经垂体系统在哺乳期，当需求 催产素（OT）的释放量很高。这种形态可塑性伴随着 谷氨酸释放突触的活性显著增加， 选择性OT神经元，这些变化包括加倍的微型 兴奋性突触后电流和增加的概率， 谷氨酸释放在GABA能中也发现了类似的上调 突触妊娠晚期性腺激素分泌的深刻变化 被认为是对这些变化进行了编程，预计OT活动会增加 神经元此外，局部OT释放反馈两种类型的突触 通过OT神经元和/或其突触前末梢上的自身受体。中央 OT释放对于形态可塑性和正常的 哺乳期间OT神经元放电的表达。本工程 这种增加的突触活动的机制和后果将是 研究了有四个具体目的：目的1）A）测试谷氨酸是否 在哺乳期间，OT神经元上AMPA/红藻氨酸受体的释放被增强， 突触前调节自身释放的变化; B）确定 NMDA受体是否参与了这种可塑性;目的2）为了检测NMDA受体是否参与了这种可塑性， γ-氨基丁酸能和谷氨酸能活性的组合和差异贡献 哺乳期OT神经元的锋电位模式;目的3）测试OT是否 OT神经元的直接和突触前效应是状态依赖性的， OT能改变哺乳期OT神经元的放电模式;目的4）检测 怀孕期间多巴胺能活动增加的时间依赖性， 以及是否受性腺类固醇激素控制。这些研究 这对于理解OT神经元的中枢控制如何适应 怀孕和哺乳期间增加激素分泌的需求。

DESCRIPTION (applicant's abstract): Neurosecretory neurons have a large capacity for morphological and physiological plasticity as a function of endocrine state during adulthood. Of principal interest in this project is the formation of new synapses in the supraoptic and paraventricular nuclei of the hypothalamo-neurohypophysial system during lactation, when the demand for oxytocin (OT) release is high. This morphological plasticity is accompanied by significant increases in the activity of glutamate-releasing synapses which are selective for OT neurons, These changes include a doubling in miniature excitatory postsynaptic currents and an increase in the probability of glutamate release. A similar up-regulation has been found for GABAergic synapses. Profound changes in gonadal hormone secretion during late pregnancy are thought to program these changes, anticipating the increased activity of OT neurons. Furthermore, local OT release feeds back on both types of synapse through autoreceptors on OT neurons and/or their presynaptic terminals. Central OT release is critical for the morphological plasticity, and for the normal expression of OT neuronal firing during lactation. In this project, the mechanisms and consequence of this increased synaptic activity will be investigated. There are four Specific Aims: Aim 1) A) To test whether glutamate release at AMPA/Kainate receptors on OT neurons is enhanced during lactation by a change in the presynaptic regulation of its own release; B) To determine whether NMDA receptors participate in this plasticity; Aim 2) To test the combined and differential contribution of GABAergic and glutamatergic activity to spike patterning in OT neurons during lactation; Aim 3) To test whether OT's direct and presynaptic effects on OT neurons are state-dependent, and whether OT can alter the firing pattern of OT neurons during lactation; Aim 4) To test the time-dependence of the increase in glutamatergic activity during pregnancy, and whether it is controlled by gonadal steroid hormones. These studies are important for understanding how the central control of OT neurons adapts to the demands of increased hormone secretion during pregnancy and lactation.