Astrocyte and L-lactate in the anterior cingulate cortex modulate schema memory and neuronal mitochondrial biogenesis
Astrocyte-derived L-lactate was shown to confer beneficial effects on synaptic plasticity and cognitive functions. However, how astrocytic Gi signaling in the anterior cingulate cortex (ACC) modulates L-lactate levels and schema memory is not clear. Here, using chemogenetic approach and well-establi...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/85751 |
| _version_ | 1797628795639824384 |
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| author | Mastura Akter Mahadi Hasan Aruna Surendran Ramkrishnan Zafar Iqbal Xianlin Zheng Zhongqi Fu Zhuogui Lei Anwarul Karim Ying Li |
| author_facet | Mastura Akter Mahadi Hasan Aruna Surendran Ramkrishnan Zafar Iqbal Xianlin Zheng Zhongqi Fu Zhuogui Lei Anwarul Karim Ying Li |
| author_sort | Mastura Akter |
| collection | DOAJ |
| description | Astrocyte-derived L-lactate was shown to confer beneficial effects on synaptic plasticity and cognitive functions. However, how astrocytic Gi signaling in the anterior cingulate cortex (ACC) modulates L-lactate levels and schema memory is not clear. Here, using chemogenetic approach and well-established behavioral paradigm, we demonstrate that astrocytic Gi pathway activation in the ACC causes significant impairments in flavor-place paired associates (PAs) learning, schema formation, and PA memory retrieval in rats. It also impairs new PA learning even if a prior associative schema exists. These impairments are mediated by decreased L-lactate in the ACC due to astrocytic Gi activation. Concurrent exogenous L-lactate administration bilaterally into the ACC rescues these impairments. Furthermore, we show that the impaired schema memory formation is associated with a decreased neuronal mitochondrial biogenesis caused by decreased L-lactate level in the ACC upon astrocytic Gi activation. Our study also reveals that L-lactate-mediated mitochondrial biogenesis is dependent on monocarboxylate transporter 2 (MCT2) and NMDA receptor activity – discovering a previously unrecognized signaling role of L-lactate. These findings expand our understanding of the role of astrocytes and L-lactate in the brain functions. |
| first_indexed | 2024-03-11T10:45:10Z |
| format | Article |
| id | doaj.art-9a8d6ab963d949eea1ba6b9df536f247 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-11T10:45:10Z |
| publishDate | 2023-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-9a8d6ab963d949eea1ba6b9df536f2472023-11-14T07:30:32ZengeLife Sciences Publications LtdeLife2050-084X2023-11-011210.7554/eLife.85751Astrocyte and L-lactate in the anterior cingulate cortex modulate schema memory and neuronal mitochondrial biogenesisMastura Akter0https://orcid.org/0000-0003-0007-6075Mahadi Hasan1Aruna Surendran Ramkrishnan2Zafar Iqbal3https://orcid.org/0000-0003-2604-7184Xianlin Zheng4Zhongqi Fu5Zhuogui Lei6Anwarul Karim7https://orcid.org/0000-0002-5795-6674Ying Li8https://orcid.org/0000-0003-3683-9695Department of Neuroscience, City University of Hong Kong, Hong Kong SAR, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, ChinaDepartment of Neuroscience, City University of Hong Kong, Hong Kong SAR, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, ChinaDepartment of Neuroscience, City University of Hong Kong, Hong Kong SAR, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, ChinaDepartment of Neuroscience, City University of Hong Kong, Hong Kong SAR, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, China; Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong SAR, ChinaDepartment of Neuroscience, City University of Hong Kong, Hong Kong SAR, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, ChinaDepartment of Neuroscience, City University of Hong Kong, Hong Kong SAR, China; Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong SAR, ChinaDepartment of Neuroscience, City University of Hong Kong, Hong Kong SAR, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, ChinaDepartment of Neuroscience, City University of Hong Kong, Hong Kong SAR, ChinaDepartment of Neuroscience, City University of Hong Kong, Hong Kong SAR, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, China; Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong SAR, China; Centre for Biosystems, Neuroscience, and Nanotechnology, City University of Hong Kong, Hong Kong SAR, ChinaAstrocyte-derived L-lactate was shown to confer beneficial effects on synaptic plasticity and cognitive functions. However, how astrocytic Gi signaling in the anterior cingulate cortex (ACC) modulates L-lactate levels and schema memory is not clear. Here, using chemogenetic approach and well-established behavioral paradigm, we demonstrate that astrocytic Gi pathway activation in the ACC causes significant impairments in flavor-place paired associates (PAs) learning, schema formation, and PA memory retrieval in rats. It also impairs new PA learning even if a prior associative schema exists. These impairments are mediated by decreased L-lactate in the ACC due to astrocytic Gi activation. Concurrent exogenous L-lactate administration bilaterally into the ACC rescues these impairments. Furthermore, we show that the impaired schema memory formation is associated with a decreased neuronal mitochondrial biogenesis caused by decreased L-lactate level in the ACC upon astrocytic Gi activation. Our study also reveals that L-lactate-mediated mitochondrial biogenesis is dependent on monocarboxylate transporter 2 (MCT2) and NMDA receptor activity – discovering a previously unrecognized signaling role of L-lactate. These findings expand our understanding of the role of astrocytes and L-lactate in the brain functions.https://elifesciences.org/articles/85751astrocytelactateschemaanterior cingulate cortexmitochondrial biogenesisDREADD |
| spellingShingle | Mastura Akter Mahadi Hasan Aruna Surendran Ramkrishnan Zafar Iqbal Xianlin Zheng Zhongqi Fu Zhuogui Lei Anwarul Karim Ying Li Astrocyte and L-lactate in the anterior cingulate cortex modulate schema memory and neuronal mitochondrial biogenesis eLife astrocyte lactate schema anterior cingulate cortex mitochondrial biogenesis DREADD |
| title | Astrocyte and L-lactate in the anterior cingulate cortex modulate schema memory and neuronal mitochondrial biogenesis |
| title_full | Astrocyte and L-lactate in the anterior cingulate cortex modulate schema memory and neuronal mitochondrial biogenesis |
| title_fullStr | Astrocyte and L-lactate in the anterior cingulate cortex modulate schema memory and neuronal mitochondrial biogenesis |
| title_full_unstemmed | Astrocyte and L-lactate in the anterior cingulate cortex modulate schema memory and neuronal mitochondrial biogenesis |
| title_short | Astrocyte and L-lactate in the anterior cingulate cortex modulate schema memory and neuronal mitochondrial biogenesis |
| title_sort | astrocyte and l lactate in the anterior cingulate cortex modulate schema memory and neuronal mitochondrial biogenesis |
| topic | astrocyte lactate schema anterior cingulate cortex mitochondrial biogenesis DREADD |
| url | https://elifesciences.org/articles/85751 |
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