Department of Neuroscience, University of Florida College of Medicine, Gainesville, FL 32610-0244, USA.
Neurobiol Aging. 2013 Mar;34(3):845-62. doi: 10.1016/j.neurobiolaging.2012.06.013. Epub 2012 Jul 18.
Both cholinergic and GABAergic projections from the rostral basal forebrain contribute to hippocampal function and mnemonic abilities. While dysfunction of cholinergic neurons has been heavily implicated in age-related memory decline, significantly less is known regarding how age-related changes in codistributed GABAergic projection neurons contribute to a decline in hippocampal-dependent spatial learning. In the current study, confocal stereology was used to quantify cholinergic (choline acetyltransferase [ChAT] immunopositive) neurons, GABAergic projection (glutamic decarboxylase 67 [GAD67] immunopositive) neurons, and total (neuronal nuclei [NeuN] immunopositive) neurons in the rostral basal forebrain of young and aged rats that were first characterized on a spatial learning task. ChAT immunopositive neurons were significantly but modestly reduced in aged rats. Although ChAT immunopositive neuron number was strongly correlated with spatial learning abilities among young rats, the reduction of ChAT immunopositive neurons was not associated with impaired spatial learning in aged rats. In contrast, the number of GAD67 immunopositive neurons was robustly and selectively elevated in aged rats that exhibited impaired spatial learning. Interestingly, the total number of rostral basal forebrain neurons was comparable in young and aged rats, regardless of their cognitive status. These data demonstrate differential effects of age on phenotypically distinct rostral basal forebrain projection neurons, and implicate dysregulated cholinergic and GABAergic septohippocampal circuitry in age-related mnemonic decline.
来自前脑基底的胆碱能和 GABA 能投射都有助于海马功能和记忆能力。虽然胆碱能神经元功能障碍与年龄相关的记忆衰退密切相关，但关于共分布的 GABA 能投射神经元如何随年龄变化导致海马依赖性空间学习能力下降的了解要少得多。在当前的研究中，使用共聚焦立体学方法来定量研究前脑基底的胆碱能（胆碱乙酰转移酶[ChAT]免疫阳性）神经元、GABA 能投射（谷氨酸脱羧酶 67 [GAD67]免疫阳性）神经元和总（神经元核[NeuN]免疫阳性）神经元在年轻和老年大鼠中的分布，这些大鼠首先在空间学习任务中进行了特征描述。老年大鼠的 ChAT 免疫阳性神经元明显但适度减少。尽管 ChAT 免疫阳性神经元数量与年轻大鼠的空间学习能力密切相关，但 ChAT 免疫阳性神经元的减少与老年大鼠的空间学习障碍无关。相比之下，在表现出空间学习障碍的老年大鼠中，GAD67 免疫阳性神经元的数量显著且选择性增加。有趣的是，无论认知状态如何，年轻和老年大鼠的前脑基底总神经元数量相当。这些数据表明年龄对前脑基底投射神经元的表型有不同的影响，并暗示胆碱能和 GABA 能隔海马回路的失调与年龄相关的记忆减退有关。
