Sexually dimorphic organization of extracellular matrix and perineuronal nets in the prairie vole (Microtus ochrogaster) social brain.

The extracellular matrix (ECM) is a fundamental component of the central nervous system that shapes neuronal communication, synaptic stability, and plasticity. Among its specialized forms, perineuronal nets (PNN) provide structural support and contribute to the regulation of circuit dynamics. Despite increasing interest in ECM function in the adult brain, its organization across species and sexes remains incompletely understood, particularly in non-traditional rodent models. Prairie voles (Microtus ochrogaster), a socially monogamous and biparental rodent, offer a valuable framework to explore ECM organization within the social brain. Here, we characterized ECM and PNN organization of social brain areas in sexually naïve adult male and female prairie voles. Using Wisteria floribunda agglutinin labeling and NeuN immunofluorescence, we quantified both ECM density and the number of PNN-positive neurons. ECM labeling revealed a heterogeneous organization, with diffuse components predominating in the olfactory bulb and more defined PNN structures in cortical and limbic regions, with a pronounced and region-specific sexual dimorphism. Males exhibited higher PNN expression or greater number of PNN-positive neurons in nucleus accumbens, lateral septum, and dentate gyrus regions, while females showed higher number of PNN-positive neurons in the anterior and posterior medial preoptic area, as well as increased labeling in hippocampal CA3. These findings reveal a mosaic pattern of ECM organization across the prairie vole brain, suggesting that PNN distribution is tailored to the functional demands of specific circuits. This work establishes a structural framework for understanding how extracellular matrix specializations may contribute to sex-dependent regulation of social and reproductive behaviors in adult mammals.