Silencing CA1 pyramidal cells output reveals the role of feedback inhibition in hippocampal oscillations
Abstract The precise temporal coordination of neural activity is crucial for brain function. In the hippocampus, this precision is reflected in the oscillatory rhythms observed in CA1. While it is known that a balance between excitatory and inhibitory activity is necessary to generate and maintain t...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-03-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-46478-3 |
| _version_ | 1797259131193655296 |
|---|---|
| author | Chinnakkaruppan Adaikkan Justin Joseph Georgios Foustoukos Jun Wang Denis Polygalov Roman Boehringer Steven J. Middleton Arthur J. Y. Huang Li-Huei Tsai Thomas J. McHugh |
| author_facet | Chinnakkaruppan Adaikkan Justin Joseph Georgios Foustoukos Jun Wang Denis Polygalov Roman Boehringer Steven J. Middleton Arthur J. Y. Huang Li-Huei Tsai Thomas J. McHugh |
| author_sort | Chinnakkaruppan Adaikkan |
| collection | DOAJ |
| description | Abstract The precise temporal coordination of neural activity is crucial for brain function. In the hippocampus, this precision is reflected in the oscillatory rhythms observed in CA1. While it is known that a balance between excitatory and inhibitory activity is necessary to generate and maintain these oscillations, the differential contribution of feedforward and feedback inhibition remains ambiguous. Here we use conditional genetics to chronically silence CA1 pyramidal cell transmission, ablating the ability of these neurons to recruit feedback inhibition in the local circuit, while recording physiological activity in mice. We find that this intervention leads to local pathophysiological events, with ripple amplitude and intrinsic frequency becoming significantly larger and spatially triggered local population spikes locked to the trough of the theta oscillation appearing during movement. These phenotypes demonstrate that feedback inhibition is crucial in maintaining local sparsity of activation and reveal the key role of lateral inhibition in CA1 in shaping circuit function. |
| first_indexed | 2024-04-24T23:04:33Z |
| format | Article |
| id | doaj.art-2da85b1e3b9e4d61898c937713e93409 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T23:04:33Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-2da85b1e3b9e4d61898c937713e934092024-03-17T12:30:58ZengNature PortfolioNature Communications2041-17232024-03-0115111510.1038/s41467-024-46478-3Silencing CA1 pyramidal cells output reveals the role of feedback inhibition in hippocampal oscillationsChinnakkaruppan Adaikkan0Justin Joseph1Georgios Foustoukos2Jun Wang3Denis Polygalov4Roman Boehringer5Steven J. Middleton6Arthur J. Y. Huang7Li-Huei Tsai8Thomas J. McHugh9Centre for Brain Research, Indian Institute of ScienceCentre for Brain Research, Indian Institute of ScienceLaboratory for Circuit and Behavioral Physiology, RIKEN Center for Brain ScienceDepartment of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of TechnologyLaboratory for Circuit and Behavioral Physiology, RIKEN Center for Brain ScienceLaboratory for Circuit and Behavioral Physiology, RIKEN Center for Brain ScienceLaboratory for Circuit and Behavioral Physiology, RIKEN Center for Brain ScienceLaboratory for Circuit and Behavioral Physiology, RIKEN Center for Brain ScienceDepartment of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of TechnologyLaboratory for Circuit and Behavioral Physiology, RIKEN Center for Brain ScienceAbstract The precise temporal coordination of neural activity is crucial for brain function. In the hippocampus, this precision is reflected in the oscillatory rhythms observed in CA1. While it is known that a balance between excitatory and inhibitory activity is necessary to generate and maintain these oscillations, the differential contribution of feedforward and feedback inhibition remains ambiguous. Here we use conditional genetics to chronically silence CA1 pyramidal cell transmission, ablating the ability of these neurons to recruit feedback inhibition in the local circuit, while recording physiological activity in mice. We find that this intervention leads to local pathophysiological events, with ripple amplitude and intrinsic frequency becoming significantly larger and spatially triggered local population spikes locked to the trough of the theta oscillation appearing during movement. These phenotypes demonstrate that feedback inhibition is crucial in maintaining local sparsity of activation and reveal the key role of lateral inhibition in CA1 in shaping circuit function.https://doi.org/10.1038/s41467-024-46478-3 |
| spellingShingle | Chinnakkaruppan Adaikkan Justin Joseph Georgios Foustoukos Jun Wang Denis Polygalov Roman Boehringer Steven J. Middleton Arthur J. Y. Huang Li-Huei Tsai Thomas J. McHugh Silencing CA1 pyramidal cells output reveals the role of feedback inhibition in hippocampal oscillations Nature Communications |
| title | Silencing CA1 pyramidal cells output reveals the role of feedback inhibition in hippocampal oscillations |
| title_full | Silencing CA1 pyramidal cells output reveals the role of feedback inhibition in hippocampal oscillations |
| title_fullStr | Silencing CA1 pyramidal cells output reveals the role of feedback inhibition in hippocampal oscillations |
| title_full_unstemmed | Silencing CA1 pyramidal cells output reveals the role of feedback inhibition in hippocampal oscillations |
| title_short | Silencing CA1 pyramidal cells output reveals the role of feedback inhibition in hippocampal oscillations |
| title_sort | silencing ca1 pyramidal cells output reveals the role of feedback inhibition in hippocampal oscillations |
| url | https://doi.org/10.1038/s41467-024-46478-3 |
| work_keys_str_mv | AT chinnakkaruppanadaikkan silencingca1pyramidalcellsoutputrevealstheroleoffeedbackinhibitioninhippocampaloscillations AT justinjoseph silencingca1pyramidalcellsoutputrevealstheroleoffeedbackinhibitioninhippocampaloscillations AT georgiosfoustoukos silencingca1pyramidalcellsoutputrevealstheroleoffeedbackinhibitioninhippocampaloscillations AT junwang silencingca1pyramidalcellsoutputrevealstheroleoffeedbackinhibitioninhippocampaloscillations AT denispolygalov silencingca1pyramidalcellsoutputrevealstheroleoffeedbackinhibitioninhippocampaloscillations AT romanboehringer silencingca1pyramidalcellsoutputrevealstheroleoffeedbackinhibitioninhippocampaloscillations AT stevenjmiddleton silencingca1pyramidalcellsoutputrevealstheroleoffeedbackinhibitioninhippocampaloscillations AT arthurjyhuang silencingca1pyramidalcellsoutputrevealstheroleoffeedbackinhibitioninhippocampaloscillations AT lihueitsai silencingca1pyramidalcellsoutputrevealstheroleoffeedbackinhibitioninhippocampaloscillations AT thomasjmchugh silencingca1pyramidalcellsoutputrevealstheroleoffeedbackinhibitioninhippocampaloscillations |