Abstract
Primarily regarded as immune proteins, chemokines are emerging as a family of molecules serving neuromodulatory functions in the developing and adult brain. Among them, CXCL12 is constitutively and widely expressed in the CNS, where it was shown to act on cellular, synaptic, network, and behavioral levels. Its receptor, CXCR4, is abundant in the amygdala, a brain structure involved in pathophysiology of anxiety disorders. Dysregulation of CXCL12/CXCR4 signaling has been implicated in anxiety-related behaviors. Here we demonstrate that exogenous CXCL12 at 2 nM but not at 5 nM increased neuronal excitability in the lateral division of the rat central amygdala (CeL) which was evident in the Late-Firing but not Regular-Spiking neurons. These effects were blocked by AMD3100, a CXCR4 antagonist. Moreover, CXCL12 increased the excitability of the neurons of the basolateral amygdala (BLA) that is known to project to the CeL. However, CXCL12 increased neither the spontaneous excitatory nor spontaneous inhibitory synaptic transmission in the CeL. In summary, the data reveal specific activation of Late-Firing CeL cells along with BLA neurons by CXCL12 and suggest that this chemokine may alter information processing by the amygdala that likely contributes to anxiety and fear conditioning.
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Data Availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.
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The code used for analysis and visualization in the current study was written in R and is available from the corresponding author upon reasonable request.
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This work was supported by the National Science Center grant number 2016/21/N/NZ4/03621 and 2019/32/T/NZ4/00592.
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All authors contributed to the study’s conception and design. Joanna Ewa Sowa performed the experiments, analyzed the data, and wrote the first draft of the manuscript. Grzegorz Hess commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Sowa, J.E., Tokarski, K. & Hess, G. Activation of the CXCR4 Receptor by Chemokine CXCL12 Increases the Excitability of Neurons in the Rat Central Amygdala. J Neuroimmune Pharmacol 19, 9 (2024). https://doi.org/10.1007/s11481-024-10112-2
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DOI: https://doi.org/10.1007/s11481-024-10112-2