Durham VA Medical Center , Duke University Medical Center, Durham, North Carolina; Department of Psychiatry , Duke University Medical Center, Durham, North Carolina; Department of Neurosugery , Duke University Medical Center, Durham, North Carolina.
Alcohol Clin Exp Res. 2013 Dec;37(12):2074-85. doi: 10.1111/acer.12204. Epub 2013 Jul 26.
Chronic alcohol use, especially exposure to alcohol during adolescence or young adulthood, is closely associated with cognitive deficits that may persist into adulthood. Therefore, it is essential to identify possible neuronal mechanisms underlying the observed deficits in learning and memory. Hippocampal interneurons play a pivotal role in regulating hippocampus-dependent learning and memory by exerting strong inhibition on excitatory pyramidal cells. The function of these interneurons is regulated not only by synaptic inputs from other types of neurons but is also precisely governed by their own intrinsic membrane ionic conductances. The voltage-gated A-type potassium current (IA ) regulates the intrinsic membrane properties of neurons, and disruption of IA is responsible for many neuropathological processes including learning and memory deficits. Thus, it represents a previously unexplored cellular mechanism whereby chronic ethanol (EtOH) may alter hippocampal memory-related functioning.
Using whole-cell electrophysiological recording methods, we investigated the enduring effects of chronic intermittent ethanol (CIE) exposure during adolescence or adulthood on IA in rat CA1 interneurons.
We found that the mean peak amplitude of IA was significantly reduced after CIE in either adolescence or adulthood, but IA density was attenuated after CIE in adolescence but not after CIE in adulthood. In addition, the voltage-dependent steady-state activation and inactivation of IA were altered in interneurons after CIE.
These findings suggest that CIE can cause long-term changes in IA channels in interneurons and thus may alter their inhibitory influences on memory-related local hippocampal circuits, which could be, in turn, responsible for learning and memory impairments observed after chronic EtOH exposure.
慢性酒精使用，特别是在青少年或成年早期暴露于酒精，与认知缺陷密切相关，这些缺陷可能会持续到成年期。因此，确定观察到的学习和记忆缺陷的潜在神经元机制至关重要。海马中间神经元通过对兴奋性锥体神经元施加强烈抑制，在调节海马依赖性学习和记忆方面发挥着关键作用。这些中间神经元的功能不仅受到来自其他类型神经元的突触输入的调节，而且还受到其自身内在膜离子电导的精确调节。电压门控 A 型钾电流（IA）调节神经元的内在膜特性，IA 的破坏是许多神经病理学过程的原因，包括学习和记忆缺陷。因此，它代表了一个以前未被探索的细胞机制，即慢性乙醇（EtOH）可能改变海马记忆相关功能。
使用全细胞膜片钳电生理记录方法，我们研究了青春期或成年期慢性间歇性乙醇（CIE）暴露对大鼠 CA1 中间神经元 IA 的持久影响。
我们发现，CIE 后无论是在青春期还是成年期，IA 的平均峰值幅度均显著降低，但 IA 密度在青春期 CIE 后降低，但在成年期 CIE 后未降低。此外，IA 的电压依赖性稳态激活和失活在 CIE 后中间神经元中发生改变。
这些发现表明，CIE 可导致中间神经元中 IA 通道的长期变化，从而可能改变它们对记忆相关局部海马回路的抑制影响，这反过来可能是慢性 EtOH 暴露后观察到的学习和记忆损伤的原因。
