Maharjan, D. M., Dai, Y. Y., Glantz, E. H., Jadhav, S. P. (November 2018) Disruption of dorsal hippocampal – prefrontal interactions using chemogenetic inactivation impairs spatial learning. Neurobiology of Learning and Memory, 155. pp. 351-360. ISSN 10747427 (ISSN)
Abstract
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 naïve 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. © 2018 Elsevier Inc.
| Item Type: | Paper |
|---|---|
| Subjects: | organs, tissues, organelles, cell types and functions > tissues types and functions > hippocampus organism description > animal behavior > learning organs, tissues, organelles, cell types and functions > tissues types and functions > prefrontal cortex |
| CSHL Authors: | |
| Communities: | CSHL labs > Kepecs lab School of Biological Sciences > Publications |
| Depositing User: | Matthew Dunn |
| Date: | November 2018 |
| Date Deposited: | 21 Sep 2018 18:50 |
| Last Modified: | 03 Jan 2019 22:00 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/37217 |
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