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

Charalambos Sigalas,Eleni Konsolaki,Irini Skaliora

doi:10.1186/s13293-017-0143-9

Charalambos Sigalas, Eleni Konsolaki + Show 1 more

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https://doi.org/10.1186/s13293-017-0143-9

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Abstract

BackgroundSeveral 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.MethodsUp 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).ResultsFemale 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.ConclusionsThe 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.

Highlights

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
Female mice exhibit increased Up state activity local field potential (LFP) recordings of spontaneous network activity were obtained from the primary somatosensory cortex of male and female mice
Our data were obtained in isolated cortical slices, we have previously shown that the stimulation of nicotinic acetylcholine receptors by endogenously released ACh reduces Up state duration and occurrence in brain slices of the somatosensory cortex of adult and old male mice [19]

Summary

Introduction

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. We employed an ex vivo preparation of network activity in the form of spontaneously recurring Up states to examine sex differences in the function of cortical microcircuits This type of synchronized activity, a characteristic of quiescent brain states, such as slow-wave sleep, anesthesia, and quiet wakefulness, is generated by the intrinsic properties of the cortical networks and is present in brain slices [35, 36]. We use animals across different stages of their reproductive life––pre-puberty, adult, and old mice––to examine the developmental trajectory between the two sexes To our knowledge, this the first study that investigates the sexual dimorphism in intrinsic cortical network function along the mouse lifespan

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