Selenium deficiency impedes maturation of parvalbumin interneurons, perineuronal nets, and neural network activity.

Selenoproteins are fundamental players in redox signaling that are essential for proper brain development and function. They are indispensable for the vitality of GABAergic parvalbumin-expressing interneurons (PVIs), a cell type characterized by fast-spiking activity and heightened rates of metabolism. During development, PVIs are preferentially encapsulated by specialized extracellular matrix structures, termed perineuronal nets (PNNs), which serve to stabilize synaptic structure and act as protective barriers against redox insults. Consequently, alterations in PVIs and PNNs are well chronicled in neuropsychiatric disease, and evidence from animal models indicates that redox imbalance during adolescence impedes their maturation. Herein, we examined the influence of selenium on maturation of neural network structure and activity in primary cortical cultures. Cultures grown in selenium-deficient media exhibited reduced antioxidant activity, impaired PNN formation, and decreased synaptic input onto PVIs at 28 days in vitro, which coincided with increased oxidative stress. Parallel studies to monitor longitudinal maturation of in vitro electrophysiological activity were conducted using microelectrode arrays (MEA). Selenium content affected the electrophysiological profile of developing cultures, as selenium-deficient cultures exhibited impairments in long-term potentiation in conjunction with reduced spike counts for both network bursts and in response to stimulation. Finally, similar PNN deficits were observed in the cortex of mice raised on a selenium-deficient diet, providing corroborative evidence for the importance of selenium in PNN development. In sum, these findings show the vital role of selenium for the development of GABAergic inhibitory circuits.