Cholecystokinin facilitates the formation of long-term heterosynaptic plasticity in the distal subiculum

Fengwen Huang; Abdul Baset; Stephen Temitayo Bello; Xi Chen; Jufang He

doi:10.1038/s42003-025-07597-9

Cholecystokinin facilitates the formation of long-term heterosynaptic plasticity in the distal subiculum

Fengwen Huang^*, Abdul Baset, Stephen Temitayo Bello, Xi Chen, Jufang He^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

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Abstract

It has been well established that Cornu Ammonis-(CA1) and subiculum (SUB) serve as the major output components of the entorhinal-hippocampal circuitry. Nevertheless, how the neuromodulators regulate the neurocircuitry in hippocampal formation has remained elusive. Cholecystokinin (CCK), is the most abundant neuropeptide in the central nervous system, which broadly regulates the animal's physiological status at multiple levels, including neuroplasticity and its behavioral consequences. Here, we uncover that exogenous CCK potentiates the excitatory synaptic transmission in the CA1-SUB projections via CCK-B receptor. Dual-color light theta burst stimulation elicits heterosynaptic long-term potentiation in distal SUB region. Light activation of medial entorhinal cortex (MEC) derived CCK-positive neurons triggers the CCK release in the SUB. Neuronal activities of SUB-projecting MEC^CCK neurons are necessary for conveying and processing of navigation-related information. In conclusion, our findings prove a crucial role of CCK in regulating neurobiological functions in the SUB region. © The Author(s) 2025

Original language	English
Article number	153
Journal	Communications Biology
Volume	8
Issue number	1
Online published	1 Feb 2025
DOIs	https://doi.org/10.1038/s42003-025-07597-9
Publication status	Published - 2025

Funding

This work was supported by Hong Kong Research Grants Council, General Research Fund: 11103220 M, 11101521 M (GRF, JFH); Hong Kong Research Grants Council, Collaborative Research Fund: C1043-21GF(CRF, JFH); Innovation and Technology Fund: MRP/053/18X, GHP_075_19GD (ITF, JFH); Health and Medical Research Fund: 06172456, 09203656 (HMRF, XC, JFH). All cartoons are created with BioRender.com (https://app.biorender.com/).

Research Keywords

Animals
Cholecystokinin/metabolism
Neuronal Plasticity/physiology
Hippocampus/physiology
Male
Mice
Long-Term Potentiation/physiology
Mice, Inbred C57BL
Entorhinal Cortex/physiology
Synaptic Transmission/physiology
Neurons/physiology
Receptor, Cholecystokinin B/metabolism
Synapses/physiology

Publisher's Copyright Statement

This full text is made available under CC-BY-NC-ND 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/

RGC Funding Information

RGC-funded

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title = "Cholecystokinin facilitates the formation of long-term heterosynaptic plasticity in the distal subiculum",

abstract = "It has been well established that Cornu Ammonis-(CA1) and subiculum (SUB) serve as the major output components of the entorhinal-hippocampal circuitry. Nevertheless, how the neuromodulators regulate the neurocircuitry in hippocampal formation has remained elusive. Cholecystokinin (CCK), is the most abundant neuropeptide in the central nervous system, which broadly regulates the animal's physiological status at multiple levels, including neuroplasticity and its behavioral consequences. Here, we uncover that exogenous CCK potentiates the excitatory synaptic transmission in the CA1-SUB projections via CCK-B receptor. Dual-color light theta burst stimulation elicits heterosynaptic long-term potentiation in distal SUB region. Light activation of medial entorhinal cortex (MEC) derived CCK-positive neurons triggers the CCK release in the SUB. Neuronal activities of SUB-projecting MECCCK neurons are necessary for conveying and processing of navigation-related information. In conclusion, our findings prove a crucial role of CCK in regulating neurobiological functions in the SUB region. {\textcopyright} The Author(s) 2025",

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author = "Fengwen Huang and Abdul Baset and Bello, {Stephen Temitayo} and Xi Chen and Jufang He",

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year = "2025",

doi = "10.1038/s42003-025-07597-9",

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volume = "8",

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AU - Huang, Fengwen

AU - Baset, Abdul

AU - Bello, Stephen Temitayo

AU - Chen, Xi

AU - He, Jufang

PY - 2025

Y1 - 2025

N2 - It has been well established that Cornu Ammonis-(CA1) and subiculum (SUB) serve as the major output components of the entorhinal-hippocampal circuitry. Nevertheless, how the neuromodulators regulate the neurocircuitry in hippocampal formation has remained elusive. Cholecystokinin (CCK), is the most abundant neuropeptide in the central nervous system, which broadly regulates the animal's physiological status at multiple levels, including neuroplasticity and its behavioral consequences. Here, we uncover that exogenous CCK potentiates the excitatory synaptic transmission in the CA1-SUB projections via CCK-B receptor. Dual-color light theta burst stimulation elicits heterosynaptic long-term potentiation in distal SUB region. Light activation of medial entorhinal cortex (MEC) derived CCK-positive neurons triggers the CCK release in the SUB. Neuronal activities of SUB-projecting MECCCK neurons are necessary for conveying and processing of navigation-related information. In conclusion, our findings prove a crucial role of CCK in regulating neurobiological functions in the SUB region. © The Author(s) 2025

AB - It has been well established that Cornu Ammonis-(CA1) and subiculum (SUB) serve as the major output components of the entorhinal-hippocampal circuitry. Nevertheless, how the neuromodulators regulate the neurocircuitry in hippocampal formation has remained elusive. Cholecystokinin (CCK), is the most abundant neuropeptide in the central nervous system, which broadly regulates the animal's physiological status at multiple levels, including neuroplasticity and its behavioral consequences. Here, we uncover that exogenous CCK potentiates the excitatory synaptic transmission in the CA1-SUB projections via CCK-B receptor. Dual-color light theta burst stimulation elicits heterosynaptic long-term potentiation in distal SUB region. Light activation of medial entorhinal cortex (MEC) derived CCK-positive neurons triggers the CCK release in the SUB. Neuronal activities of SUB-projecting MECCCK neurons are necessary for conveying and processing of navigation-related information. In conclusion, our findings prove a crucial role of CCK in regulating neurobiological functions in the SUB region. © The Author(s) 2025

KW - Animals

KW - Cholecystokinin/metabolism

KW - Neuronal Plasticity/physiology

KW - Hippocampus/physiology

KW - Male

KW - Mice

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KW - Mice, Inbred C57BL

KW - Entorhinal Cortex/physiology

KW - Synaptic Transmission/physiology

KW - Neurons/physiology

KW - Receptor, Cholecystokinin B/metabolism

KW - Synapses/physiology

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ER -

Cholecystokinin facilitates the formation of long-term heterosynaptic plasticity in the distal subiculum

Abstract

Funding

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HMRF: CCK-B Receptor Antagonist for the Treatment of Depression in the Mouse Model

GRF: Gene Therapy for Epilepsy through Enhancing Inhibition with High-Frequency Activation of GABAergic Neurons in Mice

GRF: A Novel CCK Receptor Regulates the Long-term Potentiation of Inhibition in the Auditory Cortex

Cite this

Cholecystokinin facilitates the formation of long-term heterosynaptic plasticity in the distal subiculum

Abstract

Funding

Research Keywords

Publisher's Copyright Statement

RGC Funding Information

Access Output

Other Access Options

Permanent Link

Other Files and Links

Fingerprint

Projects

HMRF: CCK-B Receptor Antagonist for the Treatment of Depression in the Mouse Model

GRF: Gene Therapy for Epilepsy through Enhancing Inhibition with High-Frequency Activation of GABAergic Neurons in Mice

GRF: A Novel CCK Receptor Regulates the Long-term Potentiation of Inhibition in the Auditory Cortex

Cite this