Department of Psychology, St. Mary's College of Maryland, 18952 E. Fisher Road, St. Mary's City, MD 20686, USA.
Neuropharmacology. 2010 Dec;59(7-8):605-11. doi: 10.1016/j.neuropharm.2010.08.012. Epub 2010 Aug 21.
The neonatal ventral hippocampal lesion (NVHL) manipulation is a neurodevelopmental animal model of schizophrenia that produces abnormalities in the prefrontal cortex and nucleus accumbens, both efferent targets of the hippocampus, and leads to spatial working memory impairments. To investigate the neuroanatomical basis of spatial working memory in NVHL animals, we assessed performance in two radial arm maze tasks known to be differentially sensitive to the two hippocampal efferent pathways, and measured levels of neuronal activation (Fos immunoreactivity [Fos-IR]) in the prefrontal cortex and nucleus accumbens following task performance. Neonatal rats (postnatal day 6-8) received excitotoxic lesions of the ventral hippocampus (n=25), or a sham procedure (infusions of artificial cerebrospinal fluid; n=22). Upon reaching adulthood, animals were trained in either a non-delayed random foraging task or a spatial delayed win-shift task. NVHL animals were impaired on the spatial delayed win-shift task, which depends on communication between hippocampus and prefrontal cortex, but were unimpaired on the non-delayed random foraging task, which requires connections between hippocampus and nucleus accumbens. Fos-IR in the nucleus accumbens was greater in NVHL animals than in shams following the random foraging task, despite similar levels of performance, while no group differences in Fos-IR in either the nucleus accumbens or prefrontal cortex were observed following win-shift performance. These results suggest that although the NVHL manipulation disrupts development of hippocampal efferents to both the prefrontal cortex and the nucleus accumbens, the disruption of hippocampal-prefrontal pathways has the dominant behavioral effect on spatial performance in NVHL rats.
新生鼠腹侧海马损伤（NVHL）操作是一种精神分裂症的神经发育动物模型，它会导致海马的两个传出靶区——前额叶皮层和伏隔核出现异常，并导致空间工作记忆损伤。为了研究 NVHL 动物的空间工作记忆的神经解剖学基础，我们评估了两种已知对海马两个传出途径具有不同敏感性的放射臂迷宫任务的表现，并在任务完成后测量了前额叶皮层和伏隔核中的神经元激活水平（Fos 免疫反应性 [Fos-IR]）。新生大鼠（出生后 6-8 天）接受腹侧海马的兴奋性损伤（n=25）或假手术（人工脑脊液输注；n=22）。成年后，动物接受非延迟随机觅食任务或空间延迟赢移任务的训练。NVHL 动物在空间延迟赢移任务中表现受损，该任务依赖于海马和前额叶皮层之间的通讯，但在非延迟随机觅食任务中不受影响，该任务需要海马和伏隔核之间的连接。NVHL 动物在随机觅食任务后的伏隔核中的 Fos-IR 高于假手术组，尽管它们的表现水平相似，而在赢移表现后，伏隔核或前额叶皮层中均未观察到 Fos-IR 的组间差异。这些结果表明，尽管 NVHL 操作破坏了海马对前额叶皮层和伏隔核的传出通路的发育，但海马-前额叶通路的破坏对 NVHL 大鼠的空间表现具有主导的行为影响。
