Perineuronal nets preferentially surround parvalbumin interneurons in the prelimbic cortex: A rat and mouse comparison.

Recent work has shown the importance of perineuronal nets (PNNs) in modulating neuronal function and plasticity. Functional studies increasingly manipulate PNNs to probe their role in learning and memory, yet interpreting these manipulations requires knowing which cell types PNNs surround, information that remains incomplete for several brain regions. This study focuses on the prelimbic cortex to determine the percentage of specific interneurons and pyramidal cells that are surrounded by PNNs in male rats and mice. We used immunohistochemistry to assess prelimbic cortex cells containing parvalbumin (PV), glutamate decarboxylase (GAD65/67), and/or calcium kinase II (CamKII), and Wisteria floribunda agglutinin to identify PNNs. Cells with PV, GAD65/67 and/or CamKII were counted and the percentage with PNNs was calculated. Among the cell types examined, PV-expressing interneurons showed the highest frequency of PNN association in the prelimbic cortex of both rats and mice, followed by GAD65/67-expressing interneurons. No CamKII-positive cells had PNNs in rats or mice. PV-only and GAD-only cells were much more likely to have PNNs in mice than in rats. In both species, a small percentage of PNNs surround cells that had no detectable immunolabeling. These findings indicate that PV interneurons are most likely to have PNNs in layers 5/6 of the prelimbic cortex, but species differences suggest caution in designing and interpreting experiments that manipulate PNNs, particularly when generalizing between rat and mouse models.