Adrenergic signalling to astrocytes in anterior cingulate cortex contributes to pain-related aversive memory in rats

Zafar Iqbal; Zhuogui Lei; Aruna S. Ramkrishnan; Shu Liu; Mahadi Hasan; Mastura Akter; Yuk Yan Lam; Ying Li

doi:10.1038/s42003-022-04405-6

Adrenergic signalling to astrocytes in anterior cingulate cortex contributes to pain-related aversive memory in rats

Zafar Iqbal, Zhuogui Lei, Aruna S. Ramkrishnan, Shu Liu, Mahadi Hasan, Mastura Akter, Yuk Yan Lam, Ying Li^*

^*Corresponding author for this work

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

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Abstract

Pain contains both sensory and affective dimensions. We identify the role of norepinephrine in colorectal distention (sub-threshold for acute pain) induced conditioned place avoidance and plasticity gene expression in the anterior cingulate cortex (ACC). Activating locus coeruleus (LC)-projecting ACC neurons facilitates pain-evoked aversive consolidation and memory, while inhibiting LC-projecting ACC neurons reversibly blocks it. Optogenetic activation of ACC astrocytes facilitates aversive behaviour. ACC astrocytic Gi manipulation suppressed aversive behaviour and early plasticity gene expression induced by opto-activation of LC neurons projecting to ACC. Evidences for the critical role of β2AR in ACC astrocytes were provided using AAV encoding β2AR miRNAi to knockdown β2AR in astrocytes. In contrast, opto-activation of ACC astrocytic β2ARs promotes aversion memory. Our findings suggest that projection-specific adrenergic astrocytic signalling in ACC is integral to system-wide neuromodulation in response to visceral stimuli, and plays a key role in mediating pain-related aversion consolidation and memory formation.

Original language	English
Article number	10
Journal	Communications Biology
Volume	6
Issue number	1
Online published	5 Jan 2023
DOIs	https://doi.org/10.1038/s42003-022-04405-6
Publication status	Published - 2023

Funding

This work was supported by the General Research Fund (GRF) of Research Grants Council of Hong Kong (11103721, 11102820, and 11100018), the National Natural Science Foundation of China (NSFC) and RGC Joint Research Scheme (3171101014, N_CityU114/17), Innovation and Technology Fund Hong Kong (CityU 9445909), the Shenzhen-Hong Kong Institute of Brain Science Innovation Open Project Contract (NYKFKT2019012). This work was also supported by City University of Hong Kong Neuroscience Research Infrastructure Grant (9610211), and Centre for Biosystems, Neuroscience, and Nanotechnology Grant (9360148). We would like to thank Dr. Suresh M Kanna for his assistance with VMR analysis.

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

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title = "Adrenergic signalling to astrocytes in anterior cingulate cortex contributes to pain-related aversive memory in rats",

abstract = "Pain contains both sensory and affective dimensions. We identify the role of norepinephrine in colorectal distention (sub-threshold for acute pain) induced conditioned place avoidance and plasticity gene expression in the anterior cingulate cortex (ACC). Activating locus coeruleus (LC)-projecting ACC neurons facilitates pain-evoked aversive consolidation and memory, while inhibiting LC-projecting ACC neurons reversibly blocks it. Optogenetic activation of ACC astrocytes facilitates aversive behaviour. ACC astrocytic Gi manipulation suppressed aversive behaviour and early plasticity gene expression induced by opto-activation of LC neurons projecting to ACC. Evidences for the critical role of β2AR in ACC astrocytes were provided using AAV encoding β2AR miRNAi to knockdown β2AR in astrocytes. In contrast, opto-activation of ACC astrocytic β2ARs promotes aversion memory. Our findings suggest that projection-specific adrenergic astrocytic signalling in ACC is integral to system-wide neuromodulation in response to visceral stimuli, and plays a key role in mediating pain-related aversion consolidation and memory formation.",

author = "Zafar Iqbal and Zhuogui Lei and Ramkrishnan, {Aruna S.} and Shu Liu and Mahadi Hasan and Mastura Akter and Lam, {Yuk Yan} and Ying Li",

year = "2023",

doi = "10.1038/s42003-022-04405-6",

language = "English",

volume = "6",

journal = "Communications Biology",

issn = "2399-3642",

publisher = "Springer Nature",

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T1 - Adrenergic signalling to astrocytes in anterior cingulate cortex contributes to pain-related aversive memory in rats

AU - Iqbal, Zafar

AU - Lei, Zhuogui

AU - Ramkrishnan, Aruna S.

AU - Liu, Shu

AU - Hasan, Mahadi

AU - Akter, Mastura

AU - Lam, Yuk Yan

AU - Li, Ying

PY - 2023

Y1 - 2023

N2 - Pain contains both sensory and affective dimensions. We identify the role of norepinephrine in colorectal distention (sub-threshold for acute pain) induced conditioned place avoidance and plasticity gene expression in the anterior cingulate cortex (ACC). Activating locus coeruleus (LC)-projecting ACC neurons facilitates pain-evoked aversive consolidation and memory, while inhibiting LC-projecting ACC neurons reversibly blocks it. Optogenetic activation of ACC astrocytes facilitates aversive behaviour. ACC astrocytic Gi manipulation suppressed aversive behaviour and early plasticity gene expression induced by opto-activation of LC neurons projecting to ACC. Evidences for the critical role of β2AR in ACC astrocytes were provided using AAV encoding β2AR miRNAi to knockdown β2AR in astrocytes. In contrast, opto-activation of ACC astrocytic β2ARs promotes aversion memory. Our findings suggest that projection-specific adrenergic astrocytic signalling in ACC is integral to system-wide neuromodulation in response to visceral stimuli, and plays a key role in mediating pain-related aversion consolidation and memory formation.

AB - Pain contains both sensory and affective dimensions. We identify the role of norepinephrine in colorectal distention (sub-threshold for acute pain) induced conditioned place avoidance and plasticity gene expression in the anterior cingulate cortex (ACC). Activating locus coeruleus (LC)-projecting ACC neurons facilitates pain-evoked aversive consolidation and memory, while inhibiting LC-projecting ACC neurons reversibly blocks it. Optogenetic activation of ACC astrocytes facilitates aversive behaviour. ACC astrocytic Gi manipulation suppressed aversive behaviour and early plasticity gene expression induced by opto-activation of LC neurons projecting to ACC. Evidences for the critical role of β2AR in ACC astrocytes were provided using AAV encoding β2AR miRNAi to knockdown β2AR in astrocytes. In contrast, opto-activation of ACC astrocytic β2ARs promotes aversion memory. Our findings suggest that projection-specific adrenergic astrocytic signalling in ACC is integral to system-wide neuromodulation in response to visceral stimuli, and plays a key role in mediating pain-related aversion consolidation and memory formation.

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JO - Communications Biology

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Adrenergic signalling to astrocytes in anterior cingulate cortex contributes to pain-related aversive memory in rats

Abstract

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GRF: Astrocyte Adrenergic Signaling in the Anterior Cingulate Cortex Contributes to Visceral Pain-Evoked Aversion in Rats

ITF-InnoHK-ExtU-Lead: Large-scale Neural Oscillations Play a Primary Role in Fundamental Cognitive Functions

GRF: Chronic Pain Induces Hypomyelination: A Causal Mechanism for Brain Circuitry Desynchronization and Impaired Decision Making.

Cite this

Adrenergic signalling to astrocytes in anterior cingulate cortex contributes to pain-related aversive memory in rats

Abstract

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Publisher's Copyright Statement

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GRF: Astrocyte Adrenergic Signaling in the Anterior Cingulate Cortex Contributes to Visceral Pain-Evoked Aversion in Rats

ITF-InnoHK-ExtU-Lead: Large-scale Neural Oscillations Play a Primary Role in Fundamental Cognitive Functions

GRF: Chronic Pain Induces Hypomyelination: A Causal Mechanism for Brain Circuitry Desynchronization and Impaired Decision Making.

Cite this