Vago David R, Kesner Raymond P
University of Utah, Department of Psychology, Salt Lake City, UT 84112, USA.
Behav Brain Res. 2008 Jun 3;189(2):273-83. doi: 10.1016/j.bbr.2008.01.002. Epub 2008 Jan 15.
Subregional analyses of the hippocampus suggest CA1-dependent memory processes rely heavily upon interactions between the CA1 subregion and entorhinal cortex. There is evidence that the direct perforant path (pp) projection to CA1 is selectively modulated by dopamine while having little to no effect on the Schaffer collateral (SC) projection to CA1. The current study takes advantage of this pharmacological dissociation to demonstrate that local infusion of the non-selective dopamine agonist, apomorphine (10, 15 microg), into the CA1 subregion of awake animals produces impairments in working memory at intermediate (5 min), but not short-term (10 s) delays within a delayed non-match-to-place task on a radial arm maze. Sustained impairments were also found in a novel context with similar object-space relationships. Infusion of apomorphine into CA1 is also shown here to produce deficits in spatial, but not non-spatial novelty detection within an object exploration paradigm. In contrast, apomorphine produces no behavioral deficits when infused into the CA3 subregion or overlying cortex. These behavioral studies are supported by previous electrophysiological data that demonstrate local infusion of the same doses of apomorphine significantly modifies evoked responses in the distal dendrites of CA1 following angular bundle stimulation, but produces no significant effects in the proximal dendritic layer following stimulation of the SC. These results support a modulatory role for dopamine in EC-CA1, but not CA3-CA1 circuitry, and suggest the possibility of a fundamental role for EC-CA1 synaptic transmission in terms of detection of spatial novelty, and intermediate-term, but not short-term spatial working memory or object-novelty detection.
海马体的亚区域分析表明，依赖CA1的记忆过程在很大程度上依赖于CA1亚区域与内嗅皮层之间的相互作用。有证据表明，直接穿通通路（pp）向CA1的投射受到多巴胺的选择性调节，而对向CA1的海马联合纤维（SC）投射几乎没有影响。本研究利用这种药理学上的分离来证明，在清醒动物的CA1亚区域局部注入非选择性多巴胺激动剂阿扑吗啡（10、15微克），会在放射状臂迷宫的延迟非匹配位置任务中，在中间延迟（5分钟）时导致工作记忆受损，但在短期延迟（10秒）时不会。在具有相似物体空间关系的新环境中也发现了持续的损伤。本文还表明，在物体探索范式中，向CA1注入阿扑吗啡会导致空间方面的缺陷，但不会导致非空间新奇性检测方面的缺陷。相比之下，当注入CA3亚区域或其上方的皮层时，阿扑吗啡不会产生行为缺陷。这些行为学研究得到了先前电生理数据的支持，这些数据表明，局部注入相同剂量的阿扑吗啡会显著改变角束刺激后CA1远端树突的诱发反应，但在刺激SC后近端树突层没有显著影响。这些结果支持多巴胺在EC-CA1而非CA3-CA1神经回路中具有调节作用，并表明EC-CA1突触传递在空间新奇性检测以及中期而非短期空间工作记忆或物体新奇性检测方面可能具有重要作用。
