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Astrocyte L-Lactate Signaling in the ACC Regulates Visceral Pain Aversive Memory in Rats.
Zafar Iqbal1,2,3, Shu Liu1,2, Zhuogui Lei1,2,3
1Department of Neuroscience, College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong 999077, China.
Cells
|January 8, 2023
Summary
Lactate released from astrocytes in the anterior cingulate cortex (ACC) drives aversive memory formation after visceral pain. This process is crucial for understanding chronic visceral pain conditions like irritable bowel syndrome (IBS).
Area of Science:
- Neuroscience
- Pain Research
- Astrocytes and Metabolism
Background:
- Pain perception involves sensory and affective components, with emotional feelings contributing to its sustained unpleasantness.
- The brain circuitry underlying pain, including memory and attention, is of significant research interest, yet specific signaling mechanisms remain unclear.
- Chronic visceral pain is a key factor in the development of irritable bowel syndrome (IBS).
Purpose of the Study:
- To investigate the role of lactate in the anterior cingulate cortex (ACC) in aversive learning and memory following visceral pain insults.
- To elucidate the signaling mechanisms by which lactate influences pain-related memory consolidation and gene expression.
- To explore the involvement of astrocytes in lactate release and their contribution to visceral pain processing.
Main Methods:
- Utilized a conditioned place avoidance (CPA) paradigm in rats with subthreshold colorectal distention (CRD) to induce pain-related aversion.
- Measured L-lactate concentrations in the ACC and administered exogenous lactate or inhibitors.
- Investigated the effects of astrocyte activation and pharmacological interventions on aversive learning, memory consolidation, and plasticity gene expression (pCREB, CREB, Erk1/2).
Main Results:
- CRD paired with a specific environment led to significant aversion, indicating pain-related aversive learning.
- L-lactate levels in the ACC increased post-CPA training; exogenous lactate enhanced aversive memory and plasticity gene expression.
- Inhibition of glycogen phosphorylation impaired memory consolidation, while astrocyte activation reduced lactate levels and suppressed aversive learning, effects reversible by lactate infusion.
Conclusions:
- Lactate is released from ACC astrocytes in vivo during visceral pain-related aversive learning and memory retrieval.
- Astrocyte-derived lactate in the ACC is essential for inducing plasticity-related immediate early genes and consolidating aversive memories.
- Astrocytic activity in the ACC plays a critical role in visceral pain-related aversive learning and memory, offering potential therapeutic targets for IBS.
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