Yamada Kazuo, McEwen Bruce S, Pavlides Constantine
The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Exp Brain Res. 2003 Sep;152(1):52-9. doi: 10.1007/s00221-003-1519-0. Epub 2003 Jul 17.
The phasic effects of stress-induced elevations of corticosterone on long-term potentiation (LTP) were investigated in the hippocampus of awake, freely behaving rats. Field potential recordings were performed in the dentate gyrus with stimulation of the medial perforant pathway or the CA1 with stimulation of the commissural/associational pathway, on the contralateral hemisphere. LTP was induced either shortly (1 h) after acute stress or 4 h later. Animals were either adrenalectomized or adrenally intact. A subgroup of animals were injected with a low dose of dexamethasone 4 h prior to the stressor, in order to suppress the corticosterone response to restraint stress, and they were tested for LTP in the dentate gyrus 4 h after the stressor. In the dentate gyrus, stress had no effect on LTP induction at 1 h post-stress; however, it produced a significant suppression at the 4 h interval. As expected, adrenalectomized rats did not show stress-suppression of LTP, but showed a lower level of LTP with or without stress. Supporting a role of stress-induced glucocorticoid secretion in LTP suppression, dexamethasone treatment of adrenally intact animals blocked the acute stress suppression of LTP in the dentate gyrus. In the CA1 field, restraint stress did not significantly affect LTP induction at either the 1- or 4-h post-stress intervals. Similarly, stress by itself, did not significantly affect neuronal excitability in either the dentate gyrus or CA1 hippocampal field at either the 1- or 4-h post-stress interval. The present results suggest that stress affects synaptic plasticity differently at the two hippocampal subfields and that the effects are time-dependent and involve the stress-induced surge of glucocorticoids.
在清醒、自由活动的大鼠海马体中，研究了应激诱导的皮质酮升高对长时程增强（LTP）的时相效应。在对侧半球，通过刺激内侧穿通通路在齿状回进行场电位记录，或通过刺激连合/联合通路在CA1区进行场电位记录。LTP在急性应激后不久（1小时）或4小时后诱导产生。动物分为肾上腺切除组或肾上腺完整组。一组动物在应激源刺激前4小时注射低剂量地塞米松，以抑制皮质酮对束缚应激的反应，并在应激源刺激后4小时测试其齿状回的LTP。在齿状回中，应激在应激后1小时对LTP诱导没有影响；然而，在4小时间隔时产生了显著抑制。正如预期的那样，肾上腺切除的大鼠没有表现出应激对LTP的抑制，但无论有无应激，其LTP水平都较低。地塞米松对肾上腺完整动物的治疗阻断了齿状回中急性应激对LTP的抑制，这支持了应激诱导的糖皮质激素分泌在LTP抑制中的作用。在CA1区，束缚应激在应激后1小时或4小时的间隔对LTP诱导均无显著影响。同样，应激本身在应激后1小时或4小时的间隔对齿状回或CA1海马区的神经元兴奋性均无显著影响。目前的结果表明，应激对两个海马亚区的突触可塑性影响不同，且这些影响是时间依赖性的，涉及应激诱导的糖皮质激素激增。
