Selective dysfunction of fast-spiking inhibitory interneurons and disruption of perineuronal nets in a tauopathy mouse model
Takehiro Kudo,
Hiroyuki Takuwa,
Manami Takahashi,
Takuya Urushihata,
Masafumi Shimojo,
Kazuaki Sampei,
Mitsugu Yamanaka,
Yutaka Tomita,
Naruhiko Sahara,
Tetsuya Suhara,
Makoto Higuchi
Affiliations
Takehiro Kudo
Sumitomo Pharma Co., Ltd., Osaka, Japan; Department of Functional Brain Imaging, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan; Collaborative Chairs Quantum Life Science·and Molecular Imaging, Tohoku University, Sendai, Japan
Hiroyuki Takuwa
Department of Functional Brain Imaging, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan; Department of Neuromapping and Neuromodulation Group, Institute for Quantum Life Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan; Corresponding author
Manami Takahashi
Department of Functional Brain Imaging, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan; Department of Neuromapping and Neuromodulation Group, Institute for Quantum Life Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan
Takuya Urushihata
Department of Functional Brain Imaging, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan
Masafumi Shimojo
Department of Functional Brain Imaging, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan
Kazuaki Sampei
Sumitomo Pharma Co., Ltd., Osaka, Japan
Mitsugu Yamanaka
Sumitomo Pharma Co., Ltd., Osaka, Japan
Yutaka Tomita
Department of Neurology, Keio University School of Medicine, Tokyo, Japan
Naruhiko Sahara
Department of Functional Brain Imaging, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan
Tetsuya Suhara
Department of Functional Brain Imaging, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan; Department of Neuromapping and Neuromodulation Group, Institute for Quantum Life Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan
Makoto Higuchi
Department of Functional Brain Imaging, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan; Corresponding author
Summary: In Alzheimer’s disease (AD), network hyperexcitability is frequently observed and associated with subsequent cognitive impairment. Dysfunction of inhibitory interneurons (INs) is thought to be one of the key biological mechanisms of hyperexcitability. However, it is still unknown how INs are functionally affected in tau pathology, which is a major pathology in AD. To clarify this, we evaluated the neuronal activity of cortical INs in 6-month-old rTg4510 mice, a model of tauopathy. Calcium imaging with mDlx enhancer-driven labeling revealed that neuronal activity in INs was decreased in rTg4510 mice. In the patch clamp recording, the firing properties of fast-spiking INs were altered so as to reduce their activity in rTg4510 mice. In parallel with microglial activation, perineuronal nets around parvalbumin-positive INs were partially disrupted in rTg4510 mice. Taken together, our data indicate that the excitability of cortical fast-spiking INs is decreased, possibly because of the disruption of perineuronal nets.
