Plasticity of Oxytocin Neurons During Lactation

描述(申请人摘要)：神经分泌神经元有一个很大的 形态和生理可塑性的能力作为 成年期的内分泌状态。这个项目的本金利息是 大鼠视上核和室旁核内新突触的形成 哺乳期间下丘脑-神经-垂体系统，当需要 催产素(OT)释放较高。这种形态可塑性伴随着 谷氨酸释放突触的活性显着增加 这些变化对OT神经元具有选择性，包括微缩倍增 兴奋性突触后电流和突触后电流的增加 谷氨酸的释放。对GABA能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 被认为策划了这些变化，预测了OT活动的增加 神经元。此外，局部OT释放对这两种类型的突触都有反馈作用 通过OT神经元和/或其突触前终末上的自身受体。中环 OT的释放对形态可塑性和正常的 催产素神经元放电在哺乳期的表达。在这个项目中， 这种突触活动增加的机制和后果将是 调查过了。它有四个具体目标：目标1)A)测试谷氨酸 催乳素可促进催产素神经元AMPA/海人藻酸受体的释放 自身释放的突触前调节的变化；B)确定 NMDA受体是否参与这种可塑性；目的2)测试 GABA能和谷氨酸能活动的联合贡献和差异性贡献 在哺乳期间刺激OT神经元的模式；目的3)测试OT的 对催产素神经元的直接和突触前效应是状态依赖的，以及 催产素可以改变催乳期催产素神经元的放电模式；目的4)测试 妊娠期间谷氨酸能活性增加的时间依赖性， 以及它是否受性腺类固醇激素控制。这些研究是 对于理解催产素神经元的中枢控制如何适应 妊娠期和哺乳期激素分泌增加的需求。

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.