Ngfr+ cholinergic projection from SI/nBM to mPFC selectively regulates temporal order recognition memory

Fan Mei, Chen Zhao, Shangjin Li, Zeping Xue, Yueyang Zhao, Yihua Xu, Rongrong Ye, He You, Peng Yu, Xinyu Han, Gregory V. Carr, Daniel R. Weinberger, Feng Yang () and Bai Lu ()
Additional contact information
Fan Mei: Peking University Health Science Center
Chen Zhao: Tsinghua University
Shangjin Li: Tsinghua University
Zeping Xue: Capital Medical University
Yueyang Zhao: Capital Medical University
Yihua Xu: Tsinghua University
Rongrong Ye: Tsinghua University
He You: Tsinghua University
Peng Yu: Tsinghua University
Xinyu Han: Tsinghua University
Gregory V. Carr: Johns Hopkins University School of Medicine
Daniel R. Weinberger: Johns Hopkins University School of Medicine
Feng Yang: Capital Medical University
Bai Lu: Tsinghua University

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: Abstract Acetylcholine regulates various cognitive functions through broad cholinergic innervation. However, specific cholinergic subpopulations, circuits and molecular mechanisms underlying recognition memory remain largely unknown. Here we show that Ngfr+ cholinergic neurons in the substantia innominate (SI)/nucleus basalis of Meynert (nBM)-medial prefrontal cortex (mPFC) circuit selectively underlies recency judgements. Loss of nerve growth factor receptor (Ngfr−/− mice) reduced the excitability of cholinergic neurons in the SI/nBM-mPFC circuit but not in the medial septum (MS)-hippocampus pathway, and impaired temporal order memory but not novel object and object location recognition. Expression of Ngfr in Ngfr−/− SI/nBM restored defected temporal order memory. Fiber photometry revealed that acetylcholine release in mPFC not only predicted object encounters but also mediated recency judgments of objects, and such acetylcholine release was absent in Ngfr−/− mPFC. Chemogenetic and optogenetic inhibition of SI/nBM projection to mPFC in ChAT-Cre mice diminished mPFC acetylcholine release and deteriorated temporal order recognition. Impaired cholinergic activity led to a depolarizing shift of GABAergic inputs to mPFC pyramidal neurons, due to disturbed KCC2-mediated chloride gradients. Finally, potentiation of acetylcholine signaling upregulated KCC2 levels, restored GABAergic driving force and rescued temporal order recognition deficits in Ngfr−/− mice. Thus, NGFR-dependent SI/nBM-mPFC cholinergic circuit underlies temporal order recognition memory.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-51707-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51707-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-51707-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().