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Rac1 GTPase activation impairs fear conditioning-induced structural changes in basolateral amygdala neurons and long-term fear memory formation

Neuropsychopharmacology volume 48, pages 1338–1346 (2023)Cite this article

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Abstract

Long-term memory formation leads to enduring alterations in synaptic efficacy and neuronal responses that may be created by changes in neuronal morphology. We show that fear conditioning leads to a long-lasting increase in the volume of the primary and secondary dendritic branches, but not of distal branches, of neurons located at the basolateral amygdala (BLA). The length of the dendritic branches is not affected by fear conditioning. Fear conditioning leads to an enduring increase in the length and volume of dendritic spines, especially in the length of the spine neck and the volume of the spine head. Fear conditioning does not affect dendritic spine density. We further reveal that activation of Rac1 in BLA during fear conditioning impairs long-term auditory, but not contextual, fear conditioning memory. Activation of Rac1 during fear conditioning prevents the enduring increase in the dendritic primary branch volume and dendritic spines length and volume. Rac1 activation per se has no effect on neuronal morphology. These results show that fear conditioning induces changes known to reduce the inhibition of signal propagation along the dendrite and the increase in synaptic efficacy whereas preventing these changes, by Rac1 activation, impairs fear memory formation.

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Fig. 1: Activation of PA-Rac1 in basolateral amygdala impairs auditory, but not contextual, fear memory formation.
Fig. 2: Fear conditioning alters dendritic shaft morphology in basolateral amygdala neurons which is prevented by Rac1 activation.
Fig. 3: Dendritic branch points in BLA neurons are increased following PA-Rac1 activation during fear conditioning.
Fig. 4: Fear conditioning induces changes in spines morphology that are prevented by Rac1 activation.

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Acknowledgements

We would like to thank Boris Shklyar from the Bioimaging Unit, Faculty of Natural Sciences, University of Haifa, for his help with the imaging. This research was supported by a grant from the Ministry of Science and Technology, Israel and the Israel Science Foundation for RL.

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  1. Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, Haifa, Israel

    Joana Freitas Costa, Monica Dines, Karishma Agarwal & Raphael Lamprecht

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Contributions

JFC performed the experiments and analyzed the data, MD performed part of the behavioral experiments, KA performed part of the behavioral experiments and RL performed the statistical analysis and wrote the paper with inputs from all authors.

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Correspondence to Raphael Lamprecht.

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Costa, J.F., Dines, M., Agarwal, K. et al. Rac1 GTPase activation impairs fear conditioning-induced structural changes in basolateral amygdala neurons and long-term fear memory formation. Neuropsychopharmacol. 48, 1338–1346 (2023). https://doi.org/10.1038/s41386-022-01518-8

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