Sex differences in endogenous cortical network activity: spontaneously recurring Up/Down states

Charalambos Sigalas, Eleni Konsolaki, Irini Skaliora

Several molecular and cellular processes in the vertebrate brain exhibit differences between males and females, leading to sexual dimorphism in the formation of neural circuits and brain organization. While studies on large-scale brain networks provide ample evidence for both structural and functional sex differences, smaller-scale local networks have remained largely unexplored. In the current study, we investigate sexual dimorphism in cortical dynamics by means of spontaneous Up/Down states, a type of network activity that is exhibited during slow-wave sleep, quiet wakefulness, and anesthesia and is thought to represent the default activity of the cortex. Up state activity was monitored by local field potential recordings in coronal brain slices of male and female mice across three ages with distinct secretion profiles of sex hormones: (i) pre-puberty (17-21 days old), (ii) 3-9 adult (months old), and (iii) old (19-24 months old). Female mice of all ages exhibited longer and more frequent Up states compared to aged-matched male mice. Power spectrum analysis revealed sex differences in the relative power of Up state events, with female mice showing reduced power in the delta range (1-4 Hz) and increased power in the theta range (4-8 Hz) compared to male mice. No sex differences were found in the characteristics of Up state peak voltage and latency. The present study revealed for the first time sex differences in intracortical network activity, using an ex vivo paradigm of spontaneously occurring Up/Down states. We report significant sex differences in Up state properties that are already present in pre-puberty animals and are maintained through adulthood and old age.