Cholecystokinin modulates age-dependent thalamocortical neuroplasticity
The thalamocortical pathways exhibit neuroplasticity not only during the critical period but also in adulthood. In this study, we investigated how cholecystokinin (CCK) modulates age-dependent thalamocortical plasticity. Our findings demonstrated that CCK is expressed in thalamocortical neurons and that high-frequency stimulation (HFS) of the thalamocortical pathway triggers the release of CCK in auditory cortex (ACx), as detected by a CCK sensor. HFS of the medial geniculate body (MGB) induced thalamocortical long-term potentiation (LTP) in wild-type young adult mice. However, knockdown of CCK expression in MGB neurons or blockade of the CCK-B receptor (CCKBR) in the ACx abolished HFS-induced LTP. Interestingly, this LTP could not be elicited in juvenile (3-week-old) or aged mice (over 18-month-old) due to distinct mechanisms: the absence of CCKBR in juveniles and the inability to release CCK in aged mice. Notably, exogenous administration of CCK into the ACx rescued LTP in aged mice and significantly improved frequency discrimination. These findings highlight the potential of CCK as a therapeutic intervention for ameliorating neuroplasticity deficits associated with thalamocortical connectivity.
Authors
- Zhoujian Xiao (ORCID: https://orcid.org/0000-0002-8316-6051)
- Peter Jendrichovsky (ORCID: https://orcid.org/0000-0003-1761-161X)
- Stephen Temitayo Bello (ORCID: https://orcid.org/0000-0002-4730-4349)
- Xuejiao Zheng
- Jufang He (ORCID: https://orcid.org/0000-0002-4288-5957)
- Xiao Li (ORCID: https://orcid.org/0000-0003-4067-6980)
- Ling He (ORCID: https://orcid.org/0000-0001-8723-7702)
- Jingyu Feng (ORCID: https://orcid.org/0000-0003-3181-4544)
- Peipei Zhou (ORCID: https://orcid.org/0000-0002-1798-3344)
- Dingxuan Zeng
- Xi Chen (ORCID: https://orcid.org/0000-0002-2144-6584)
- Hao Li (ORCID: https://orcid.org/0000-0001-8710-1290)
- Tao Chen (ORCID: https://orcid.org/0000-0003-1956-0553)
- Xue Wang (ORCID: https://orcid.org/0000-0002-7563-963X)
- Mengying Chen (ORCID: https://orcid.org/0000-0002-7819-4875)
- Mengfan Zhang (ORCID: https://orcid.org/0000-0002-8655-5247)
- Xiaohan Hu (ORCID: https://orcid.org/0000-0001-5040-6023)
Institutions
- City University of Hong Kong (HK)
- University of Rochester Medical Center (US)
- City University of Hong Kong, Shenzhen Research Institute (CN)
- Shenzhen Institutes of Advanced Technology (CN)
Publication Details
- Journal
- eLife
- Published
- 2024-10-14
- DOI
- https://doi.org/10.7554/elife.101513
- Primary Topic
- Neuropeptides and Animal Physiology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- City University of Hong Kong
- Croucher Foundation
- Karolinska Institutet
- East China Normal University
- Peking University
- Innovation and Technology Fund
- Health and Medical Research Fund