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首页> 外文期刊>Neurobiology of learning and memory >Disruption of dorsal hippocampal - prefrontal interactions using chemogenetic inactivation impairs spatial learning
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Disruption of dorsal hippocampal - prefrontal interactions using chemogenetic inactivation impairs spatial learning

机译：使用化学灭活损害空间学习的背部海马 - 前额叶相互作用的破坏

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The hippocampus (HPC) and prefrontal cortex (PFC) are both necessary for learning and memory-guided behavior. Multiple direct and indirect anatomical projections connect the two regions, and HPC - PFC functional interactions are mediated by diverse physiological network patterns, thought to sub serve various memory processes. Disconnection experiments using contralateral inactivation approaches have established the role of direct, ipsilateral projections from ventral and intermediate HPC (vHPC and iHPC) to PFC in spatial memory. However, numerous studies have also prominently implicated physiological interactions between dorsal HPC (dHPC) and PFC regions in spatial memory tasks, and recent reports have identified direct dHPC - PFC connections. Whether dHPC - PFC interactions are necessary for spatial learning and memory has yet to be tested. Here, we used a chemogenetic inactivation approach using virally-expressed DREADDs (designer receptors exclusively activated by designer drugs) in rats to investigate the role of dHPC - PFC interactions in learning a hippocampal dependent spatial alternation task. We implemented a rapid learning paradigm for a continuous W-track spatial alternation task comprising two components: an outbound, working memory component, and an inbound, spatial reference memory component. We investigated the effect of contralateral inactivation of dHPC and PFC on learning this task as compared with naive and vehicle injection controls, as well as ipsilateral inactivation of the same regions. Contralateral dHPC - PFC inactivation selectively led to a significant impairment in learning the spatial working memory task compared to control groups, but did not impair learning of the spatial reference memory task. Ipsilateral inactivation animals showed similar learning rates as animals in the control groups. In a separate experiment, we confirmed that bilateral inactivation of PFC also leads to an impairment in learning the spatial working memory task. Our results thus demonstrate that dHPC - PFC interactions are necessary for spatial alternation learning in novel tasks. In addition, they provide crucial evidence to support the view that physiological interactions between dHPC and PFC play a key role in spatial learning and memory.
机译：海马（HPC）和前额叶皮质（PFC）都是学习和记忆引导行为所必需的。多个直接和间接解剖投影连接两个区域，HPC - PFC功能相互作用由不同的生理网络模式介导，以为亚提供各种存储器过程。使用对侧灭活方法的断开实验已经建立了直接，远侧投影在空间记忆中对腹侧和中间HPC（VHPC和IHPC）至PFC的作用。然而，许多研究也突出地将背部HPC（DHPC）和空间存储器任务中的PFC区域之间的生理相互作用突出，而最近的报告已经确定了DHPC - PFC连接。 DHPC - PFC互动是空间学习和内存是否尚未进行测试。在这里，我们使用了在大鼠中使用病毒表达的Dreadds（专门激活的设计者受体）的化学灭活方法，以研究DHPC - PFC相互作用在学习海马依赖空间交替任务时的作用。我们为包括两个组件的连续W轨道空间交替任务实现了一种快速学习范例：出站，工作存储器组件和入站空间参考存储器组件。我们调查了DHPC和PFC对侧灭活的影响与幼稚和载体注射控制相比，与幼稚和载体注射控制相比，以及同一地区的同侧失活。对侧DHPC - PFC失活在与对照组相比，学习空间工作存储器任务的显着损害，但没有损害空间参考记忆任务的学习。 Ipsilidalal灭活动物显示与对照组中的动物类似的学习速率。在一个单独的实验中，我们证实，PFC的双边灭活也会导致学习空间工作记忆任务的损害。因此，我们的结果表明DHPC - PFC相互作用是新型任务中的空间交替学习所必需的。此外，他们提供了关键的证据，以支持DHPC与PFC之间的生理相互作用在空间学习和记忆中发挥关键作用。

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