Neurogenic-dependent changes in hippocampal circuitry underlie the procognitive effect of exercise in aging mice

Xiaoqing Alice Zhou; Daniel G Blackmore; Junjie Zhuo; Fatima A Nasrallah; XuanVinh To; Nyoman D Kurniawan; Alison Carlisle; King-Year Vien; Kai-Hsiang Chuang; Tianzi Jiang; Perry F Bartlett

doi:10.1016/j.isci.2021.103450

Neurogenic-dependent changes in hippocampal circuitry underlie the procognitive effect of exercise in aging mice

iScience. 2021 Nov 16;24(12):103450. doi: 10.1016/j.isci.2021.103450. eCollection 2021 Dec 17.

Authors

Xiaoqing Alice Zhou¹, Daniel G Blackmore¹, Junjie Zhuo^{1

2}, Fatima A Nasrallah^{1

3}, XuanVinh To¹, Nyoman D Kurniawan³, Alison Carlisle¹, King-Year Vien¹, Kai-Hsiang Chuang^{1

3}, Tianzi Jiang^{1

2}, Perry F Bartlett¹

Affiliations

¹ Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
² Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.
³ Centre for Advanced Imaging, The University of Queensland, Brisbane, QLD 4072, Australia.

Abstract

We have shown that the improvement in hippocampal-based learning in aged mice following physical exercise observed is dependent on neurogenesis in the dentate gyrus (DG) and is regulated by changes in growth hormone levels. The changes in neurocircuitry, however, which may underlie this improvement, remain unclear. Using in vivo multimodal magnetic resonance imaging to track changes in aged mice exposed to exercise, we show the improved spatial learning is due to enhanced DG connectivity, particularly the strengthening of the DG-Cornu Ammonis 3 and the DG-medial entorhinal cortex connections in the dorsal hippocampus. Moreover, we provide evidence that these changes in circuitry are dependent on neurogenesis since they were abrogated by ablation of newborn neurons following exercise. These findings identify the specific changes in hippocampal circuitry that underlie the cognitive improvements resulting from physical activity and show that they are dependent on the activation of neurogenesis in aged animals.

Keywords: Behavioral neuroscience; Biological sciences; cognitive neuroscience.