Abstract
Degradation of the chondroitin sulfate proteoglycans of the extracellular matrix (ECM) by injections of the bacterial enzyme chondroitinase ABC (ChABC) in the basolateral amygdala (BLA) does not impair fear memory formation but accelerates its extinction and disrupts its reactivation. These observations suggest that the treatment might selectively interfere with the post-extinction features of neurons that mediate the reinstatement of fear. Here, we report that ChABC mice show regular fear memory and memory-driven c-fos activation and dendritic spine formation in the BLA. These mice then rapidly extinguish their fear response and exhibit a post-extinction concurrent reduction in c-fos activation and large dendritic spines that extends to the anterior cingulate cortex 7 days later. At this remote time point, fear renewal and fear retrieval are impaired. These findings show that a non-cellular component of the brain tissue controls post-extinction levels of neuronal activity and spine enlargement in the regions sequentially remodelled during the formation of recent and remote fear memory. By preventing BLA and aCC neurons to retain neuronal features that serve to reactivate an extinguished fear memory, ECM digestion might offer a therapeutic strategy for durable attenuation of traumatic memories.
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19 September 2022
A Correction to this paper has been published: https://doi.org/10.1007/s00429-022-02567-x
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Acknowledgements
This work was supported by CNR-National Research Council of Italy (AGESPAN Project), Fondazione Santa Lucia, and Ministry of Health (Progetto di ricerca finalizzata No. RF-2009-153607).
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Supplementary Fig. 5 Confirming that the treatment did not interfere with the formation of the tone-shock association, ChABC- and PBS-injected mice showed the same amount of freezing during the first minute of exposure to the CS alone on the first extinction trial (PDF 438 kb)
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Pignataro, A., Pagano, R., Guarneri, G. et al. Extracellular matrix controls neuronal features that mediate the persistence of fear. Brain Struct Funct 222, 3889–3898 (2017). https://doi.org/10.1007/s00429-017-1440-0
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DOI: https://doi.org/10.1007/s00429-017-1440-0