Artificial fluorescent sensor reveals pre-synaptic NMDA receptors switch cholecystokinin release and LTP in the hippocampus

Yin-Ting Wong; Xuejiao Zheng; Siu-Hin Lau; Ka-Hei Murphy Sun; Xi Chen; Huangcan Li; Siu-Lung Ng; He Hai Jiang; Geoffrey Chun Yue Lau; Jufang He

doi:10.1111/jnc.16128

Artificial fluorescent sensor reveals pre-synaptic NMDA receptors switch cholecystokinin release and LTP in the hippocampus

Yin-Ting Wong, Xuejiao Zheng, Siu-Hin Lau, Ka-Hei Murphy Sun, Xi Chen, Huangcan Li, Siu-Lung Ng, He Hai Jiang, Geoffrey Chun Yue Lau, 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

Cholecystokinin (CCK) has been confirmed to be essential in NMDA-dependent long-term potentiation (LTP) at mouse cortical synapses. This paper has proven that CCK is necessary for LTP induced by high-frequency stimulation of mouse hippocampal synapses projected from the entorhinal cortex. We show that the subunit of the axonal NMDA receptor dominant modulates the activity-induced LTP by triggering pre-synaptic CCK release. A functional pre-synaptic NMDA receptor is required to induce LTP mediated by the axonal Ca²⁺elevation and CCK exocytosis at CCK-specific neurons. Genetic depletion of the GluN1 subunit of NMDA receptors on CCK neurons, which projected from the entorhinal cortex largely abolished the axonal Ca²⁺ elevation and disturbed the secretion of CCK in hippocampus. These results demonstrate that activity-induced LTP at the hippocampal synapse is CCK-dependent, and CCK secretion from the axonal terminal is modulated by pre-synaptic NMDA receptors. (Figure presented.) © 2024 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

Original language	English
Pages (from-to)	2621-2639
Journal	Journal of Neurochemistry
Volume	168
Issue number	9
Online published	15 May 2024
DOIs	https://doi.org/10.1111/jnc.16128
Publication status	Published - Sept 2024

Funding

This work was supported by the General Research Fund under the Hong Kong Research Grants Council (Project Ref. Number: CityU 11101521; CityU 11103922; CityU 11104923), The Collaborative Research Fund under Hong Kong Research Grants Council (Project Ref. Number: C1043\u201021G), The Innovation and Technology Fund of the Hong Kong SAR (Project Ref. Number: GHP_075_19GD), Innovation Technology Commission of the Hong Kong SAR (Project Ref. Number: Health@InnoHK program), Hong Kong Health Bureau, Health and Medical Research Fund (Project Ref. Number: 09203656; 08194106), Theme\u2010Based Research Scheme under Hong Kong Research Grants Council (Project Ref. Number: T13\u2010605/18\u2010W), Senior Research Fellow Scheme under Hong Kong Research Grants Council (Project Ref. Number: SRFS2324\u20101S02), and The College Research Grant from Hong Kong Tung Wah College (Ref: 2023\u201000\u201051 CRG230204). We would like to acknowledge the technical office of the Department of Biomedical Science and the Department of Neuroscience, The City University of Hong Kong, for providing the equipment support and Mr. Eduardo Lau for administrative and technicalassistance. We also thank the following charitable foundations for their generous support to J.H: Wong Chun Hong Endowed Chair Professorship, Charlie Lee Charitable Foundation, and Fong Shu Fook Tong Foundation.

Research Keywords

Ca2+
cholecystokinin
hippocampus
long-term potentiation
NMDA receptor

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

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title = "Artificial fluorescent sensor reveals pre-synaptic NMDA receptors switch cholecystokinin release and LTP in the hippocampus",

abstract = "Cholecystokinin (CCK) has been confirmed to be essential in NMDA-dependent long-term potentiation (LTP) at mouse cortical synapses. This paper has proven that CCK is necessary for LTP induced by high-frequency stimulation of mouse hippocampal synapses projected from the entorhinal cortex. We show that the subunit of the axonal NMDA receptor dominant modulates the activity-induced LTP by triggering pre-synaptic CCK release. A functional pre-synaptic NMDA receptor is required to induce LTP mediated by the axonal Ca2+ elevation and CCK exocytosis at CCK-specific neurons. Genetic depletion of the GluN1 subunit of NMDA receptors on CCK neurons, which projected from the entorhinal cortex largely abolished the axonal Ca2+ elevation and disturbed the secretion of CCK in hippocampus. These results demonstrate that activity-induced LTP at the hippocampal synapse is CCK-dependent, and CCK secretion from the axonal terminal is modulated by pre-synaptic NMDA receptors. (Figure presented.) {\textcopyright} 2024 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.",

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author = "Yin-Ting Wong and Xuejiao Zheng and Siu-Hin Lau and Sun, {Ka-Hei Murphy} and Xi Chen and Huangcan Li and Siu-Lung Ng and Jiang, {He Hai} and Lau, {Geoffrey Chun Yue} and Jufang He",

year = "2024",

month = sep,

doi = "10.1111/jnc.16128",

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issn = "0022-3042",

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AU - Wong, Yin-Ting

AU - Zheng, Xuejiao

AU - Lau, Siu-Hin

AU - Sun, Ka-Hei Murphy

AU - Chen, Xi

AU - Li, Huangcan

AU - Ng, Siu-Lung

AU - Jiang, He Hai

AU - Lau, Geoffrey Chun Yue

AU - He, Jufang

PY - 2024/9

Y1 - 2024/9

N2 - Cholecystokinin (CCK) has been confirmed to be essential in NMDA-dependent long-term potentiation (LTP) at mouse cortical synapses. This paper has proven that CCK is necessary for LTP induced by high-frequency stimulation of mouse hippocampal synapses projected from the entorhinal cortex. We show that the subunit of the axonal NMDA receptor dominant modulates the activity-induced LTP by triggering pre-synaptic CCK release. A functional pre-synaptic NMDA receptor is required to induce LTP mediated by the axonal Ca2+ elevation and CCK exocytosis at CCK-specific neurons. Genetic depletion of the GluN1 subunit of NMDA receptors on CCK neurons, which projected from the entorhinal cortex largely abolished the axonal Ca2+ elevation and disturbed the secretion of CCK in hippocampus. These results demonstrate that activity-induced LTP at the hippocampal synapse is CCK-dependent, and CCK secretion from the axonal terminal is modulated by pre-synaptic NMDA receptors. (Figure presented.) © 2024 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

AB - Cholecystokinin (CCK) has been confirmed to be essential in NMDA-dependent long-term potentiation (LTP) at mouse cortical synapses. This paper has proven that CCK is necessary for LTP induced by high-frequency stimulation of mouse hippocampal synapses projected from the entorhinal cortex. We show that the subunit of the axonal NMDA receptor dominant modulates the activity-induced LTP by triggering pre-synaptic CCK release. A functional pre-synaptic NMDA receptor is required to induce LTP mediated by the axonal Ca2+ elevation and CCK exocytosis at CCK-specific neurons. Genetic depletion of the GluN1 subunit of NMDA receptors on CCK neurons, which projected from the entorhinal cortex largely abolished the axonal Ca2+ elevation and disturbed the secretion of CCK in hippocampus. These results demonstrate that activity-induced LTP at the hippocampal synapse is CCK-dependent, and CCK secretion from the axonal terminal is modulated by pre-synaptic NMDA receptors. (Figure presented.) © 2024 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

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Artificial fluorescent sensor reveals pre-synaptic NMDA receptors switch cholecystokinin release and LTP in the hippocampus

Abstract

Funding

Research Keywords

Publisher's Copyright Statement

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GRF: Cholecystokinin from the Thalamocortical Projection Facilitates Heterosynaptic Visual Inputs in the Auditory Cortex and Visuoauditory Association

SRFS: The Medial Prefrontal Cortex Facilitates Learning and Memory in the Auditory Cortex Through the Medial Temporal Lobe

GRF: Heterosynaptic Neuroplasticity of the Ascending Inputs in the Auditory Thalamus by Corticothalamic Modulation

Cite this

Artificial fluorescent sensor reveals pre-synaptic NMDA receptors switch cholecystokinin release and LTP in the hippocampus

Abstract

Funding

Research Keywords

Publisher's Copyright Statement

RGC Funding Information

Access Output

Other Access Options

Permanent Link

Other Files and Links

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Projects

GRF: Cholecystokinin from the Thalamocortical Projection Facilitates Heterosynaptic Visual Inputs in the Auditory Cortex and Visuoauditory Association

SRFS: The Medial Prefrontal Cortex Facilitates Learning and Memory in the Auditory Cortex Through the Medial Temporal Lobe

GRF: Heterosynaptic Neuroplasticity of the Ascending Inputs in the Auditory Thalamus by Corticothalamic Modulation

Cite this