LACTATION--BIOLOGY & GENE EXPRESSION OF OXYTOCIN NEURONS

目的是确定在哺乳期催产素(OT)是否具有可塑性。 神经元涉及原癌基因c-fos，如果该基因表达 与脑脊液中OT的升高有关。这个 可塑性的生理后果以及它们是否需要OT或 伽马氨基丁酸(GABA)也将被研究。这项研究已经 对生殖、内分泌学和癌症的影响。 可塑性是与生长有关的新的可逆突触的形成 以及神经元的适应性。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。突触的这些变化 脑室(Icv)注射催产素可产生形态 被认为是OT神经元同步放电所必需的 吸奶。C-fos的表达可能与突触重构有关。 催乳期的OT神经元，因为这个原癌基因与 其他神经系统的可塑性。我们将用有意识的 大鼠脑脊液中OT水平的变化是否与c-fos的表达相关 妊娠、哺乳期OT神经元中FOS或其编码蛋白FOS的表达 或哺乳，或在输注OT后(Icv)。 进一步提出，OT诱导的塑性变化降低了 催产素神经元在哺乳期对渗透压刺激的反应性 一种涉及抑制性神经递质GABA的机制。新的突触 哺乳期OT神经元中含有GABA及其受体的研究 C-fos基因表达受刺激后细胞内蛋白质增加 扑热息痛。因此，使用受体激动剂和拮抗剂，我们将 检查在渗透刺激过程中OT的释放是否减弱 哺乳需要OT或GABA。此外，我们将在麻醉后确定 无论是处女鼠还是哺乳期大鼠，GABA或其拮抗剂都会改变放电 催产素神经元对渗透压刺激的阈值和最大值 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，脑脊液推挽灌流，电生理记录和 大细胞系统的刺激、Northern印迹、狭缝印迹和In 原位杂交法检测c-fos、免疫印迹和 Fos蛋白的免疫细胞化学鉴定。

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.