Greenberg Anastasia, Ward-Flanagan Rachel, Dickson Clayton T, Treit Dallas
Centre for Neuroscience, University of Alberta, Edmonton, Alberta.
Hippocampus. 2014 Nov;24(11):1308-16. doi: 10.1002/hipo.22312. Epub 2014 Jun 17.
Although hippocampal function is typically described in terms of memory, recent evidence suggests a differentiation along its dorsal/ventral axis, with dorsal regions serving memory and ventral regions serving emotion. While long-term memory is thought to be dependent on de novo protein synthesis because it is blocked by translational inhibitors such as anisomycin (ANI), online (moment-to-moment) functions of the hippocampus (such as unconditioned emotional responding) should not be sensitive to such manipulations since they are unlikely to involve neuroplasticity. However, ANI has recently been shown to suppress neural activity which suggests (1) that protein synthesis is critical for neural function and (2) that paradigms using ANI are confounded by its inactivating effects. We tested this idea using a neurobehavioral assay which compared the influence of intrahippocampal infusions of ANI at dorsal and ventral sites on unconditioned emotional behavior of rats. We show that ANI infusions in ventral, but not dorsal, hippocampus produced a suppression of anxiety-related responses in two well-established rodent tests: the elevated plus maze and shock-probe burying tests. These results are similar to those previously observed when ventral hippocampal activity is directly suppressed (e.g., by using sodium channel blockers). The present study offers compelling behavioral evidence for the proposal that ANI adversely affects ongoing neural function and therefore its influence is not simply limited to impairing the consolidation of long-term memories
尽管海马体功能通常是从记忆方面来描述的，但最近的证据表明，沿着其背侧/腹侧轴存在分化，背侧区域负责记忆，腹侧区域负责情绪。虽然长期记忆被认为依赖于从头合成蛋白质，因为它会被诸如茴香霉素（ANI）等翻译抑制剂阻断，但海马体的即时（逐时）功能（如无条件情绪反应）不应对这种操作敏感，因为它们不太可能涉及神经可塑性。然而，最近已证明ANI会抑制神经活动，这表明（1）蛋白质合成对神经功能至关重要，以及（2）使用ANI的实验范式因其失活作用而混淆不清。我们使用一种神经行为测定法来测试这一观点，该方法比较了在背侧和腹侧部位海马体内注射ANI对大鼠无条件情绪行为的影响。我们发现，在两种成熟的啮齿动物测试中：高架十字迷宫和电击探针掩埋测试，向腹侧而非背侧海马体注射ANI会抑制与焦虑相关的反应。这些结果与之前直接抑制腹侧海马体活动（例如使用钠通道阻滞剂）时观察到的结果相似。本研究为ANI对正在进行的神经功能产生不利影响这一观点提供了令人信服的行为证据，因此其影响不仅仅局限于损害长期记忆的巩固。
