Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, Florida 32610-0244, USA.
J Neurophysiol. 2010 Aug;104(2):607-16. doi: 10.1152/jn.00278.2010. Epub 2010 May 26.
Dysregulation of the cholinergic transmitter system is a hallmark of Alzheimer's disease and contributes to an age-associated decline in memory performance. The current study examined the influence of carbachol, a cholinergic receptor agonist, on synaptic transmission over the course of aging. Extracellular excitatory postsynaptic field potentials were recorded from CA3-CA1 synapses in acute hippocampal slices obtained from young adult (5-8 mo) and aged (22-24 mo) male Fischer 344 rats. Bath application of carbachol elicited a transient depression of synaptic transmission, which was followed by a long-lasting depression (CCh-LTD) observed 90 min after carbachol cessation in both age groups. However, the magnitude of CCh-LTD was significantly larger in senescent animals and was attenuated by N-methyl-D-aspartate receptor blockade in aged animals. Blockade of L-type Ca(2+) channels inhibited CCh-LTD to a greater extent in aged animals compared to young adults. Finally, the expression of CCh-LTD was dependent on protein synthesis. The results indicate that altered Ca(2+) homeostasis or muscarinic activation of Ca(2+) signaling contribute to the enhanced CCh-LTD during senescence.
胆碱能递质系统的失调是阿尔茨海默病的一个标志，并导致与年龄相关的记忆表现下降。本研究考察了乙酰胆碱，一种胆碱能受体激动剂，对衰老过程中突触传递的影响。从年轻成年（5-8 个月）和老年（22-24 个月）雄性 Fischer 344 大鼠的急性海马切片中记录 CA3-CA1 突触的细胞外兴奋性突触后场电位。在两个年龄组中，乙酰胆碱的浴施加引发了突触传递的短暂抑制，随后在乙酰胆碱停止后 90 分钟观察到长时程抑制（CCh-LTD）。然而，在衰老动物中，CCh-LTD 的幅度明显更大，并且在老年动物中被 N-甲基-D-天冬氨酸受体阻断所减弱。与年轻成年人相比，L 型钙（Ca 2+）通道的阻断在老年动物中更能抑制 CCh-LTD。最后，CCh-LTD 的表达依赖于蛋白质合成。结果表明，钙（Ca 2+）稳态的改变或钙（Ca 2+）信号的毒蕈碱激活导致衰老过程中 CCh-LTD 的增强。
