Miklós I H, Kovács K J
Laboratory of Molecular Neuroendocrinology, Institute of Experimental Medicine, Szigony u 43 H-1083, Budapest, Hungary.
Neuroscience. 2002;113(3):581-92. doi: 10.1016/s0306-4522(02)00147-1.
GABA has been identified as an important neurotransmitter in stress-related circuitry mediating inhibitory effects on neurosecretory neurons that comprise the central limb of the hypothalamo-pituitary-adrenocortical axis. Using combinations of pre-embedding immunostaining and postembedding immunogold methods at the ultrastructural level, direct synaptic contacts were revealed between GABA-containing terminals and neurosecretory cells that were immunoreactive for corticotropin-releasing hormone (CRH) in the hypothalamic paraventricular nucleus (PVN). The vast majority of axo-dendritic GABA synapses was symmetric (inhibitory) type, and 46% of all synaptic boutons in the medial parvocellular subdivision of the PVN were immunoreactive to GABA. Using the disector method, an unbiased stereological method on serial ultrathin sections, the total calculated number of synaptic contacts within the medial parvocellular subdivision of the PVN was 55.4 x 10(6)/mm(3). On CRH-positive profiles 20.1 x 10(6) GABAergic synaptic boutons were detected per mm(3) in control, colchicine-treated rats. In the medial parvocellular subdivision, 79% of GABAergic boutons terminated on CRH neurons. Following adrenalectomy, which increases the synthetic and secretory activities of CRH neurons, the number of GABAergic synapses that terminate on CRH-positive profiles was increased by 55%. GABA-containing boutons appeared to be swollen, while the contact surfaces of cellular membranes between GABAergic boutons and CRH-positive profiles were shorter in adrenalectomized animals than in controls. Our data provide ultrastructural evidence for direct inhibitory GABAergic control of stress-related CRH neurons and suggest a pivotal role of GABA-containing inputs in the functional plasticity of parvocellular neurosecretory neurons seen in response to adrenalectomy.
γ-氨基丁酸（GABA）已被确定为应激相关神经回路中的一种重要神经递质，它对构成下丘脑-垂体-肾上腺皮质轴中枢部分的神经分泌神经元具有抑制作用。运用包埋前免疫染色和包埋后免疫金法相结合的方法，在超微结构水平上揭示了下丘脑室旁核（PVN）中含GABA的终末与促肾上腺皮质激素释放激素（CRH）免疫反应阳性的神经分泌细胞之间存在直接的突触联系。绝大多数轴-树突型GABA突触为对称（抑制性）类型，PVN内侧小细胞亚区所有突触小体中有46%对GABA呈免疫反应。采用对连续超薄切片的无偏倚立体学方法——分割法，计算得出PVN内侧小细胞亚区内突触联系的总数为55.4×10⁶/mm³。在对照的、经秋水仙碱处理的大鼠中，每立方毫米CRH阳性神经元上检测到20.1×10⁶个GABA能突触小体。在内侧小细胞亚区，79%的GABA能突触小体终止于CRH神经元上。肾上腺切除术后，CRH神经元的合成和分泌活动增强，终止于CRH阳性神经元上的GABA能突触数量增加了55%。在肾上腺切除的动物中，含GABA的突触小体似乎肿胀，而GABA能突触小体与CRH阳性神经元之间细胞膜的接触面积比对照组的短。我们的数据为应激相关CRH神经元的直接抑制性GABA能控制提供了超微结构证据，并表明含GABA的输入在肾上腺切除后可见的小细胞神经分泌神经元功能可塑性中起关键作用。
