Kv3.1 Voltage-gated Potassium Channels Modulate Anxiety-like Behaviors in Female Mice

Neuroscience. 2024 Feb 6:538:68-79. doi: 10.1016/j.neuroscience.2023.12.011. Epub 2023 Dec 28.

Abstract

Inhibitory parvalbumin (PV) interneurons regulate the activity of neural circuits within brain regions involved in emotional processing, including the prefrontal cortex (PFC). Recently, rodent studies have implicated a stress-induced increase in prefrontal PV neuron activity in the development of anxiety behaviors, particularly in females. However, the mechanisms through which stress increases activity of prefrontal PV neurons remain unknown. The fast-spiking properties of PV neurons in part come from their expression of voltage-gated potassium (K+) ion channels, particularly Kv3.1 channels. We therefore suggest that stress-induced changes in Kv3.1 channels contribute to the appearance of an anxious phenotype following chronic stress in female mice. Here, we first showed that unpredictable chronic mild stress (UCMS) increased expression of Kv3.1 channels on prefrontal PV neurons in female mice, a potential mechanism underlying the previously observed hyperactivity of these neurons after stress. We then showed that female mice deficient in Kv3.1 channels displayed resilience to UCMS-induced anxiety-like behaviors. Altogether, our findings implicate Kv3.1 channels in the development of anxiety-like behaviors following UCMS, particularly in females, providing a novel mechanism to understand sex-specific vulnerabilities to stress-induced psychopathologies.

Keywords: anxiety; chronic stress; parvalbumin neurons; potassium channels.

MeSH terms

  • Animals
  • Anxiety / metabolism
  • Brain / metabolism
  • Female
  • Interneurons / metabolism
  • Male
  • Mice
  • Neurons / metabolism
  • Potassium Channels, Voltage-Gated* / metabolism
  • Shaw Potassium Channels / metabolism

Substances

  • Potassium Channels, Voltage-Gated
  • Shaw Potassium Channels