전희철 (University of California Irvine School of Medicine) | 한빛사논문 > 한빛사

한빛사논문

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University of California Irvine School of Medicine

Neuron, Available online 21 July 2020.107 1-18, 2020 | https://doi.org/10.1016/j.neuron.2020.06.023 Disrupted Place Cell Remapping and Impaired Grid Cells in a Knockin Model of Alzheimer's Disease

Heechul Jun^1,2,3,*, Allen Bramian¹, Shogo Soma^1,6, Takashi Saito^4,7, Takaomi C. Saido⁴, Kei M. Igarashi^1,2,3,5,8,*

¹Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, USA
²Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, CA, USA
³Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA
⁴Lab for Proteolytic Neuroscience, RIKEN Center for Brain Science, Wako, Saitama 351-0106, Japan
⁵Japan Science and Technology Agency, Tokyo, Japan

^*Corresponding author

Abstract

Patients with Alzheimer's disease (AD) suffer from spatial memory impairment and wandering behavior, but the brain circuit mechanisms causing such symptoms remain largely unclear. In healthy brains, spatially tuned hippocampal place cells and entorhinal grid cells exhibit distinct spike patterns in different environments, a circuit function called “remapping.” We tested remapping in amyloid precursor protein knockin (APP-KI) mice with impaired spatial memory. CA1 neurons, including place cells, showed disrupted remapping, although their spatial tuning was only mildly diminished. Medial entorhinal cortex (MEC) neurons severely lost their spatial tuning and grid cells were almost absent. Fast gamma oscillatory coupling between the MEC and CA1 was also impaired. Mild disruption of MEC grid cells emerged in younger APP-KI mice, although the spatial memory and CA1 remapping of the animals remained intact. These results point to remapping impairment in the hippocampus, possibly linked to grid cell disruption, as circuit mechanisms underlying spatial memory impairment in AD.

논문정보

형식Research article
게재일2020년 07월 (BRIC 등록일 2020-07-24)
연구진국외 연구진
분야 생명과학 > 생리학

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