Characterization of age-related changes in synaptic transmission onto F344 rat basal forebrain cholinergic neurons using a reduced synaptic preparation
Characterization of age-related changes in synaptic transmission onto F344 rat basal forebrain cholinergic neurons using a reduced synaptic preparation
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DOI：
10.1152/jn.00129.2013
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发表时间：
2014-01-01
影响因子：
2.5
通讯作者：
Murchison, David
中科院分区：
文献类型：
--
作者：
Griffith, William H.;DuBois, Dustin W.;Murchison, David
基底前脑 (BF) 胆碱能神经元参与许多在衰老过程中受损的认知过程。我们之前发现，大鼠胆碱能 BF 神经元中与年龄相关的 Ca2+ 缓冲增强与水迷宫空间学习任务中的表现受损有关（Murchison D、McDermott AN、Lasarge CL、Peebles KA、Bizon JL 和 Griffith WH. J Neurophysicalol 102：2194-2207，2009）。改变 Ca2+ 缓冲可能导致认知障碍的一种方式涉及突触功能。在本报告中，我们表明 BF 中的突触传递会随着年龄和认知状态而改变。我们检查了胆碱能 BF 神经元中自发突触后电流 (sPSC) 的特性，这些神经元已从行为特征 F344 大鼠中机械解离，无需酶。这些分离的神经元在其体细胞和近端树突上保留了功能性突触前末梢。使用全细胞膜片钳记录，我们表明 sPSC 和微型 PSC 主要是 GABA 能（荷包牡丹碱敏感），并且在所有方面都与 BF 体外切片制备中记录的 PSC 非常相似。使用水迷宫对成年（4-7 个月）和老年（22-24 个月）雄性大鼠进行认知评估。使用单细胞 RT-PCR 事后鉴定神经元表型。随着年龄的增长，sPSC 的频率会降低，这在认知障碍受试者中最为明显。这与细胞内 Ca2+ 缓冲增加的群体相同。我们还表明，增加年轻 BF 神经元突触末端的 Ca2+ 缓冲可以模拟在老年 BF 神经元中观察到的 sPSC 频率降低。
Basal forebrain (BF) cholinergic neurons participate in a number of cognitive processes that become impaired during aging. We previously found that age-related enhancement of Ca2+ buffering in rat cholinergic BF neurons was associated with impaired performance in the water maze spatial learning task (Murchison D, McDermott AN, Lasarge CL, Peebles KA, Bizon JL, and Griffith WH. J Neurophysiol 102: 2194-2207, 2009). One way that altered Ca2+ buffering could contribute to cognitive impairment involves synaptic function. In this report we show that synaptic transmission in the BF is altered with age and cognitive status. We have examined the properties of spontaneous postsynaptic currents (sPSCs) in cholinergic BF neurons that have been mechanically dissociated without enzymes from behaviorally characterized F344 rats. These isolated neurons retain functional presynaptic terminals on their somata and proximal dendrites. Using whole cell patch-clamp recording, we show that sPSCs and miniature PSCs are predominately GABAergic (bicuculline sensitive) and in all ways closely resemble PSCs recorded in a BF in vitro slice preparation. Adult (4-7 mo) and aged (22-24 mo) male rats were cognitively assessed using the water maze. Neuronal phenotype was identified post hoc using single-cell RT-PCR. The frequency of sPSCs was reduced during aging, and this was most pronounced in cognitively impaired subjects. This is the same population that demonstrated increased intracellular Ca2+ buffering. We also show that increasing Ca2+ buffering in the synaptic terminals of young BF neurons can mimic the reduced frequency of sPSCs observed in aged BF neurons.