Pavlides C, McEwen B S
Rockefeller University, New York, NY 10021, USA.
Brain Res. 1999 Dec 18;851(1-2):204-14. doi: 10.1016/s0006-8993(99)02188-5.
We have previously shown that the two types of adrenal steroid receptors, mineralocorticoid MR. and glucocorticoid GR. produce opposite effects on long-term potentiation LTP. in the dentate gyrus in vivo. and CA1 hippocampal field in vitro. More specifically, MR activation enhanced and prolonged LTP, whereas GR activation suppressed LTP in these areas and also produced a long-term depression LTD. of the synaptic response. In the present experiment we investigated acute effects of MR and GR activation on LTP induction in the mossy fiber and commissural associational input to the CA3 hippocampal field, since the mechanisms underlying LTP induction in these two pathways differ, the former being N-methyl-D-aspartate receptor NMDAR. independent while the latter being NMDAR-dependent. Rats were either adrenalectomized ADX or adrenally intact. ADX animals were acutely injected with either the specific MR agonist, aldosterone, the specific GR agonist RU 28362 or vehicle. One hour following the injection, the animals were prepared for electrophysiological recording stimulation. Field potential recordings were performed in the radiatum or laconosum moleculare layers of the CA3 field, with stimulation of either the mossy fibers or the commissural associational input from the contralateral hemisphere. We also replicated our previous findings by recording in the dentate gyrus with stimulation of the medial perforant pathway, in the same animals. As observed in our previous study in the dentate gyrus, we found an enhancement and a suppression of LTP with MR and GR activation, respectively. Similarly, for the commissural associational input to CA3, MR activation enhanced LTP, while GR activation reduced it. In contrast, for the mossy fiber input to CA3, neither MR nor GR activation significantly affected LTP induction. These results indicate that adrenal steroids may modulate LTP induction in the hippocampus via an interaction with glutamatergic NMDAR.
我们之前已经表明，两种肾上腺类固醇受体，即盐皮质激素受体（MR）和糖皮质激素受体（GR），对体内齿状回和体外海马CA1区的长时程增强（LTP）产生相反的作用。更具体地说，MR激活增强并延长了LTP，而GR激活则抑制了这些区域的LTP，并且还产生了突触反应的长时程抑制（LTD）。在本实验中，我们研究了MR和GR激活对海马CA3区苔藓纤维和联合联络输入中LTP诱导的急性影响，因为这两条通路中LTP诱导的潜在机制不同，前者不依赖N-甲基-D-天冬氨酸受体（NMDAR），而后者依赖NMDAR。大鼠要么接受肾上腺切除术（ADX），要么肾上腺完整。给ADX动物急性注射特异性MR激动剂醛固酮、特异性GR激动剂RU 28362或溶剂。注射后1小时，将动物准备好进行电生理记录刺激。在CA3区的辐射层或分子层进行场电位记录，刺激苔藓纤维或来自对侧半球的联合联络输入。我们还通过在同一动物的齿状回中记录内侧穿通通路的刺激来重复我们之前的发现。正如我们之前在齿状回研究中所观察到的，我们分别发现MR和GR激活时LTP增强和抑制。同样，对于CA3区的联合联络输入，MR激活增强了LTP，而GR激活则降低了LTP。相比之下，对于CA3区的苔藓纤维输入，MR和GR激活均未显著影响LTP诱导。这些结果表明，肾上腺类固醇可能通过与谷氨酸能NMDAR相互作用来调节海马中的LTP诱导。
