LACTATION--BIOLOGY & GENE EXPRESSION OF OXYTOCIN NEURONS

目的是确定在哺乳期，催产素（OT）的可塑性 神经元涉及原癌基因c-fos，如果该基因表达 与脑脊液（CSF）中OT升高相关。 的 可塑性的生理后果，以及它们是否需要OT或 还将研究γ-氨基丁酸（GABA）。 本研究 对生殖、内分泌和癌症的影响。 可塑性是指涉及生长的新的可逆突触的形成 和神经元的适应。 大细胞系统中的OT神经元经历 从妊娠中期到哺乳期的可塑性。 这些突触的变化 脑室内（icv）灌注OT可产生形态学改变 并且被认为是OT神经元的同步放电所必需的， 吮吸 c-fos的表达被认为是突触重建的基础。 OT神经元在哺乳期，因为这种原癌基因已与 其他神经系统的可塑性。 我们将研究，使用意识 大鼠，CSF中OT水平的变化是否与c- fos及其编码蛋白fos在妊娠期、哺乳期OT神经元中的表达 或在哺乳期，或在OT输注（icv）后。 进一步提出，OT诱导的可塑性变化降低了 OT神经元对泌乳期间渗透刺激的反应性， 一种涉及抑制性神经递质GABA的机制。 新突触 哺乳期OT神经元上的GABA和GABA受体 当c-fos的表达被刺激时， 美曲唑 因此，使用受体激动剂和拮抗剂，我们将 检查是否OT对渗透刺激的衰减释放， 哺乳需要OT或GABA。 同时，我们将在麻醉状态下 处女或哺乳期大鼠是否GABA或其拮抗剂改变放电 OT神经元对渗透刺激的反应率或阈值和最大值 通过电刺激释放OT的频率 大细胞神经元 技术将包括：OT的RIA和 加压素，CSF推拉灌注，电生理记录和 大细胞系统的刺激、北方印迹、狭缝印迹和 原位杂交用于评估c-fos的mRNA，免疫印迹和 免疫细胞化学鉴定Fos蛋白。

The goals are to determine if during lactation, plasticity in oxytocin (OT) neurons involves the proto-oncogene c-fos, and if this gene expression correlates with a rise in OT in cerebrospinal fluid (CSF). The physiological consequences of plasticity and whether they require OT or gamma-aminobutyric acid (GABA) will also be studied. This research has implications for reproduction, endocrinology and cancer. Plasticity is the formation of new and reversible synapses involving growth and adaptation of neurons. OT neurons in the magnocellular system undergo plasticity from mid-gestation through lactation. These changes in synaptic morphology can be produced by intracerebroventricular (icv) infusion of OT and are believed necessary for the synchronized firing of OT neurons during suckling. Expression of c-fos is postulated in synaptic remodeling of the OT neuron during lactation since this proto-oncogene has been associated with plasticity of other neural systems. We will examine, using conscious rats, whether changes in OT levels in CSF correlate with expression of c- fos or its encoded protein, fos, in OT neurons during gestation, lactation or suckling, or after infusion (icv) of OT. It is proposed further, that OT-induced changes in plasticity decrease the responsiveness of the OT neuron to osmotic stimulation during lactation by a mechanism involving the inhibitory neurotransmitter, GABA. New synapses on the OT neuron during lactation contain GABA and the GABA receptor protein increases in cells when expression of c-fos is stimulated by Metrazole. Therefore, using receptor agonists and antagonists we will examine whether the attenuated release of OT to osmotic stimulation during lactation requires OT or GABA. Also, we will determine in anesthetized virgin or lactating rats whether GABA or its antagonist alters the firing rate of OT neurons to osmotic stimulation or the threshold and maximal frequency at which OT is released by electrical stimulation of magnocellular neurons. Techniques will include: RIA of OT and vasopressin, push-pull perfusion of CSF, electrophysiological recording and stimulation of the magnocellular system, Northern blot, slot blot and in situ hybridization for assessing mRNA for c-fos, and immunoblot and immunocytochemistry for identifying fos protein.