Noradrenergic inputs from the locus coeruleus to anterior piriform cortex and the olfactory bulb modulate olfactory outputs
Abstract Norepinephrine (NE) released from locus coeruleus (LC) noradrenergic (NAergic) neurons plays a pivotal role in the regulation of olfactory behaviors. However, the precise circuits and receptor mechanisms underlying this function are not well understood. Here, in DBH-Cre mice model, we show...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55609-9 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841559219338215424 |
|---|---|
| author | Chi Geng Ruochen Li Shan Li Penglai Liu Yuxin Peng Changyu Liu Zhen Wang Hongxing Zhang Anan Li |
| author_facet | Chi Geng Ruochen Li Shan Li Penglai Liu Yuxin Peng Changyu Liu Zhen Wang Hongxing Zhang Anan Li |
| author_sort | Chi Geng |
| collection | DOAJ |
| description | Abstract Norepinephrine (NE) released from locus coeruleus (LC) noradrenergic (NAergic) neurons plays a pivotal role in the regulation of olfactory behaviors. However, the precise circuits and receptor mechanisms underlying this function are not well understood. Here, in DBH-Cre mice model, we show that LC NAergic neurons project directly to both anterior piriform cortex (aPC) and the olfactory bulb (OB). By using pharmacological and optogenetic manipulations in vitro and in vivo, we found that NE reduces the excitability of aPC pyramidal neurons directly via α2 receptors and that it bidirectionally regulates the activity of OB mitral cells via modulation of inhibitory inputs. Activation of the NAergic projection reduced both spontaneous and odor-evoked activity in the aPC/OB in awake mice, enhanced the odor-decoding ability of the aPC, and decreased the odor-decoding ability of the OB. Furthermore, activation of LC–aPC/OB NAergic projections accelerated odor discrimination and specific inactivation of the LC–aPC/OB NAergic pathway impaired olfactory detection and discrimination. These findings identify the mechanism underlying NAergic modulation of the aPC/OB and elucidate its role in odor processing and olfactory behaviors. |
| format | Article |
| id | doaj-art-71d6e7e2b42d42f5a5a42d0d56b67be8 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-71d6e7e2b42d42f5a5a42d0d56b67be82025-01-05T12:40:46ZengNature PortfolioNature Communications2041-17232025-01-0116111810.1038/s41467-024-55609-9Noradrenergic inputs from the locus coeruleus to anterior piriform cortex and the olfactory bulb modulate olfactory outputsChi Geng0Ruochen Li1Shan Li2Penglai Liu3Yuxin Peng4Changyu Liu5Zhen Wang6Hongxing Zhang7Anan Li8Jiangsu Key Laboratory of Brain Disease and Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical UniversityJiangsu Key Laboratory of Brain Disease and Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical UniversityJiangsu Key Laboratory of Brain Disease and Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical UniversityJiangsu Key Laboratory of Brain Disease and Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical UniversityJiangsu Key Laboratory of Brain Disease and Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical UniversityJiangsu Key Laboratory of Brain Disease and Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical UniversityJiangsu Key Laboratory of Brain Disease and Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical UniversityJiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical UniversityJiangsu Key Laboratory of Brain Disease and Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical UniversityAbstract Norepinephrine (NE) released from locus coeruleus (LC) noradrenergic (NAergic) neurons plays a pivotal role in the regulation of olfactory behaviors. However, the precise circuits and receptor mechanisms underlying this function are not well understood. Here, in DBH-Cre mice model, we show that LC NAergic neurons project directly to both anterior piriform cortex (aPC) and the olfactory bulb (OB). By using pharmacological and optogenetic manipulations in vitro and in vivo, we found that NE reduces the excitability of aPC pyramidal neurons directly via α2 receptors and that it bidirectionally regulates the activity of OB mitral cells via modulation of inhibitory inputs. Activation of the NAergic projection reduced both spontaneous and odor-evoked activity in the aPC/OB in awake mice, enhanced the odor-decoding ability of the aPC, and decreased the odor-decoding ability of the OB. Furthermore, activation of LC–aPC/OB NAergic projections accelerated odor discrimination and specific inactivation of the LC–aPC/OB NAergic pathway impaired olfactory detection and discrimination. These findings identify the mechanism underlying NAergic modulation of the aPC/OB and elucidate its role in odor processing and olfactory behaviors.https://doi.org/10.1038/s41467-024-55609-9 |
| spellingShingle | Chi Geng Ruochen Li Shan Li Penglai Liu Yuxin Peng Changyu Liu Zhen Wang Hongxing Zhang Anan Li Noradrenergic inputs from the locus coeruleus to anterior piriform cortex and the olfactory bulb modulate olfactory outputs Nature Communications |
| title | Noradrenergic inputs from the locus coeruleus to anterior piriform cortex and the olfactory bulb modulate olfactory outputs |
| title_full | Noradrenergic inputs from the locus coeruleus to anterior piriform cortex and the olfactory bulb modulate olfactory outputs |
| title_fullStr | Noradrenergic inputs from the locus coeruleus to anterior piriform cortex and the olfactory bulb modulate olfactory outputs |
| title_full_unstemmed | Noradrenergic inputs from the locus coeruleus to anterior piriform cortex and the olfactory bulb modulate olfactory outputs |
| title_short | Noradrenergic inputs from the locus coeruleus to anterior piriform cortex and the olfactory bulb modulate olfactory outputs |
| title_sort | noradrenergic inputs from the locus coeruleus to anterior piriform cortex and the olfactory bulb modulate olfactory outputs |
| url | https://doi.org/10.1038/s41467-024-55609-9 |
| work_keys_str_mv | AT chigeng noradrenergicinputsfromthelocuscoeruleustoanteriorpiriformcortexandtheolfactorybulbmodulateolfactoryoutputs AT ruochenli noradrenergicinputsfromthelocuscoeruleustoanteriorpiriformcortexandtheolfactorybulbmodulateolfactoryoutputs AT shanli noradrenergicinputsfromthelocuscoeruleustoanteriorpiriformcortexandtheolfactorybulbmodulateolfactoryoutputs AT penglailiu noradrenergicinputsfromthelocuscoeruleustoanteriorpiriformcortexandtheolfactorybulbmodulateolfactoryoutputs AT yuxinpeng noradrenergicinputsfromthelocuscoeruleustoanteriorpiriformcortexandtheolfactorybulbmodulateolfactoryoutputs AT changyuliu noradrenergicinputsfromthelocuscoeruleustoanteriorpiriformcortexandtheolfactorybulbmodulateolfactoryoutputs AT zhenwang noradrenergicinputsfromthelocuscoeruleustoanteriorpiriformcortexandtheolfactorybulbmodulateolfactoryoutputs AT hongxingzhang noradrenergicinputsfromthelocuscoeruleustoanteriorpiriformcortexandtheolfactorybulbmodulateolfactoryoutputs AT ananli noradrenergicinputsfromthelocuscoeruleustoanteriorpiriformcortexandtheolfactorybulbmodulateolfactoryoutputs |