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bioRxiv · 10.1101/2020.10.09.332965

Sex-specific maturational trajectory of endocannabinoid plasticity in the rat prefrontal cortex

Bernabeu, A.·Bara, A.·Manduca, A.·Borsoi, M.·Lassalle, O.·Pelissier-Alicot, A.-L.·MANZONI, O. J.
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Abstract

The prefrontal cortex (PFC) develops until early adulthood in rodents and humans, but how synaptic plasticity evolves throughout postnatal development is not known. Here, we used a cross-sectional approach to establish the postnatal maturational trajectories of intrinsic properties and synaptic plasticity in the PFC of rats of both sexes. We found that while layer 5 PFC pyramidal neurons from rats of both sexes displayed similar current-voltage relationships, rheobases and resting potentials across all age groups, excitability was lower in female adults compared to the other developmental stages. NMDAR-dependent long-term potentiation and mGluR2/3-mediated long-term depression (LTD) were equally expressed at the juvenile, pubescent and adult developmental stages in animals of both sexes. However, the developmental course of endocannabinoid (eCB)-mediated LTD was sexually dimorphic. First, eCB-LTD emerged during the juvenile period in females. However, although CB1Rs were functional in both sexes at all developmental stages, eCB-LTDs first emerged during pubescence in male. Second, eCB-LTD engaged distinct receptors in males and females depending on their developmental stages. Female rats employ both CB1R and TRPV1R to produce eCB-LTD at the juvenile stage but solely CB1R at pubescence followed by only TRPV1R at adulthood. In contrast, in pubescent and adult males eCB-LTD always and exclusively depended on CB1R. Pharmacological blockade of 2AGs principal degrading enzyme allowed incompetent male juvenile synapses to express eCB-LTD. The data reveal different maturational trajectories in the PFC of male and female rats and provide new cellular substrates to the sex-specific behavioral and synaptic abnormalities caused by adolescent exposure to cannabinoids.

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Bernabeu, A., Bara, A., Manduca, A., Borsoi, M., Lassalle, O., Pelissier-Alicot, A.-L., MANZONI, O. J.. 2020-10-10. Sex-specific maturational trajectory of endocannabinoid plasticity in the rat prefrontal cortex. https://doi.org/10.1101/2020.10.09.332965

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