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Altered Hippocampal–Prefrontal Dynamics Following Medial Prefrontal Stroke in Mouse

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Abstract

Frontal infarcts can produce cognitive impairments that affect an individual’s ability to function in everyday life. However, the precise types of deficits, and their underlying mechanisms, are not well-understood. Here we used a prefrontal photothrombotic stroke model in C57BL/6J mice to characterise specific cognitive changes that occur in the 6 weeks post-stroke. Behavioural experiments were paired with in vivo electrophysiology to assess whether changes in oscillatory communication between the prefrontal cortex (PFC) and the hippocampus (HPC) mirrored any observed behavioural changes. We found that mice in the stroke group exhibited a delayed onset impairment in tasks of spatial working memory (object location recognition and Y-maze) and that this correlated with reduced PFC–HPC theta band coherence (5–12 Hz) during the task. In the open field, mice in the stroke group exhibited hyperactivity as compared to controls, and stroke animals also exhibited significantly higher beta band activity (13–30 Hz) in the PFC and the HPC. Taken together our results suggest that infarcts in the PFC result in PFC–HPC oscillatory communication changes in the theta and beta bands, correlating with altered performance in spatial memory and open field tasks respectively. Of particular interest, early open field changes in PFC beta band power post-stroke correlated to later-stage spatial memory impairments, highlighting this as a potential biomarker for detecting when spatial memory impairments are likely to occur.

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Acknowledgements

This project was supported by Marsden Grant #UOO1407 administered by The Royal Society of New Zealand.

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Correspondence to Andrew N. Clarkson.

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The authors confirm that there are no conflicts of interest in the present research.

Ethical Approval

All experimental protocols were approved by the University of Otago Animal Ethics Committee (AEC Protocol 13/15), which adheres to the New Zealand Animal Welfare Act 1999. All procedures were carried out in accordance with the ARRIVE guidelines with mice being assigned to either stroke or sham experimental groups at the time of surgery by one member of staff, ensuring all behavioural and electrophysiological procedures were undertaken in a blind manner.

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Hillman, K.L., Wall, H.J., Matthews, L.O. et al. Altered Hippocampal–Prefrontal Dynamics Following Medial Prefrontal Stroke in Mouse. Neuromol Med 21, 401–413 (2019). https://doi.org/10.1007/s12017-019-08557-3

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  • DOI: https://doi.org/10.1007/s12017-019-08557-3

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