TY - JOUR
T1 - Neurogenic-dependent changes in hippocampal circuitry underlie the procognitive effect of exercise in aging mice
AU - Zhou, Xiaoqing Alice
AU - Blackmore, Daniel G.
AU - Zhuo, Junjie
AU - Nasrallah, Fatima A.
AU - To, Xuan Vinh
AU - Kurniawan, Nyoman D.
AU - Carlisle, Alison
AU - Vien, King Year
AU - Chuang, Kai-Hsiang
AU - Jiang, Tianzi
AU - Bartlett, Perry F.
N1 - Funding Information:
This study was supported by National Health and Medical Research Council Project Grant (GNT1130141 to P.F.B. and D.G.B) and grant from the Stafford Fox Medical Research Foundation (P.F.B). We thank the staff of the University of Queensland Biological Resources Facility for breeding and maintaining the animals in this study, Rowan Tweedale and Megan Alexander for editorial assistance, and Nick Valmas for assistance with illustrations. Imaging was performed at the Queensland Brain Institute's Advanced Microscopy Facility. Behavioral tests were performed at the Queensland Brain Institute's Behavior and Surgical Facility. The authors acknowledge the 9.4-T MRI facility and scientific and technical assistance of the National Imaging Facility, a National Collaborative Research Infrastructure Strategy (NCRIS) capability, at the Center for Advanced Imaging, The University of Queensland. X.A.Z. D.G.B. J.Z. X.T. N.D.K. A.C. and K-Y.V. performed the experiments, X.A.Z. D.G.B. and P.F.B. conceived the experiments, X.A.Z, D.G.B. F.N. K-H.C. T.J. and P.F.B analyzed the data and wrote the manuscript. The authors declare no competing interests.
Funding Information:
This study was supported by National Health and Medical Research Council Project Grant ( GNT1130141 to P.F.B. and D.G.B) and grant from the Stafford Fox Medical Research Foundation (P.F.B). We thank the staff of the University of Queensland Biological Resources Facility for breeding and maintaining the animals in this study, Rowan Tweedale and Megan Alexander for editorial assistance, and Nick Valmas for assistance with illustrations. Imaging was performed at the Queensland Brain Institute's Advanced Microscopy Facility. Behavioral tests were performed at the Queensland Brain Institute's Behavior and Surgical Facility. The authors acknowledge the 9.4-T MRI facility and scientific and technical assistance of the National Imaging Facility, a National Collaborative Research Infrastructure Strategy (NCRIS) capability, at the Center for Advanced Imaging, The University of Queensland.
Publisher Copyright:
© 2021 The Author(s)
PY - 2021/12/17
Y1 - 2021/12/17
N2 - 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.
AB - 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.
KW - Behavioral neuroscience
KW - Biological sciences
KW - cognitive neuroscience
UR - http://www.scopus.com/inward/record.url?scp=85119967361&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2021.103450
DO - 10.1016/j.isci.2021.103450
M3 - Article
C2 - 34877505
AN - SCOPUS:85119967361
SN - 2589-0042
VL - 24
JO - iScience
JF - iScience
IS - 12
M1 - 103450
ER -