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In vivo calcium imaging through microendoscopic lenses enables imaging of previously inaccessible neuronal populations deep within the brains of freely moving animals. However, it is computationally challenging to extract single-neuronal activity from microendoscopic data, because of the very large background fluctuations and high spatial overlaps intrinsic to this recording modality. Here, we describe a new constrained matrix factorization approach to accurately separate the background and then demix and denoise the neuronal signals of interest. We compared the proposed method against previous independent components analysis and constrained nonnegative matrix factorization approaches. On both simulated and experimental data recorded from mice, our method substantially improved the quality of extracted cellular signals and detected more well-isolated neural signals, especially in noisy data regimes. These advances can in turn significantly enhance the statistical power of downstream analyses, and ultimately improve scientific conclusions derived from microendoscopic data.

Prairie vole breeder pairs form monogamous pair bonds, which are maintained through the expression of selective aggression toward novel conspecifics. Here, we utilize behavioral and anatomical techniques to extend the current understanding of neural mechanisms that mediate pair bond maintenance. For both sexes, we show that pair bonding up-regulates mRNA expression for genes encoding D1-like dopamine (DA) receptors and dynorphin as well as enhances stimulated DA release within the nucleus accumbens (NAc). We next show that D1-like receptor regulation of selective aggression is mediated through downstream activation of kappa-opioid receptors (KORs) and that activation of these receptors mediates social avoidance. Finally, we also identified sex-specific alterations in KOR binding density within the NAc shell of paired males and demonstrate that this alteration contributes to the neuroprotective effect of pair bonding against drug reward. Together, these findings suggest motivational and valence processing systems interact to mediate the maintenance of social bonds.