| Autor: |
Moustafa Algamal, Alyssa N. Russ, Morgan R. Miller, Steven S. Hou, Megi Maci, Leon P. Munting, Qiuchen Zhao, Dmitry Gerashchenko, Brian J. Bacskai, Ksenia V. Kastanenka |
| Rok vydání: |
2022 |
| Předmět: |
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| Popis: |
Alzheimer’s disease (AD) is characterized by synaptic loss and neuronal network dysfunction. These network deficits are mediated by early alterations in neuronal firing rates that coincide with amyloid plaque accumulation. Mounting evidence supports that inhibitory networks are impaired in AD, but the mechanisms driving these inhibitory deficits are poorly understood. Here we use in vivo multiphoton calcium imaging to determine the relationship between amyloid accumulation and the spontaneous activity of excitatory neurons and inhibitory interneurons in an APP/PS1 mouse model of Alzheimer’s disease. We show that somatostatin-expressing (SOM) interneurons are hyperactive, while parvalbumin-expressing interneurons are hypoactive in APP/PS1 mice. Only SOM interneuron hyperactivity correlated with proximity to amyloid plaque. These inhibitory deficits were accompanied by decreased excitatory neurons activity and decreased pairwise activity correlations in APP/PS1 mice. Our study identifies cell-specific interneuronal firing deficits driven by amyloid pathology in APP/PS1 mice and provides new insights for targeting inhibitory circuits in Alzheimer’s disease. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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