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Authors & Affiliations
Benjamin Campbell, Pegah Chehrazi, Maria Isabel Carreño-Muñoz, Graziella Di Cristo
Abstract
Hormones regulate brain function to achieve adaptive cognitive and behavioural responses. Consequently, disruption of sex hormone signaling may underlie some aspects of sex and gender bias in psychiatric and developmental brain disorder frequency and presentation. Currently, the basis by which sex steroid hormones (e.g. estradiol) alter sensory processing and cortical function is largely unexplored, as most research focuses on impacts within the hypothalamus and limbic system. Therefore, mechanistic insight is needed to understand the fundamental organization of sex hormone action on cortical cell types and circuits. Estradiol, the major estrogen in mammals, alters neuronal activity and transcriptional programs to affect neuron function. The ovarian cycle (estrous cycle in mice), presents with four main phases characterized by a large variation in circulating sex hormone levels, importantly including estradiol. The auditory cortex is a useful comparative model to study the cell, circuit, and molecular mechanisms of sex hormone signaling, as it is modified by the ovarian cycle and estradiol across species (including in mice and humans). We used chronic in vivo electrode recordings to measure auditory cortical electrical activity across estrous phases in female mice, revealing effects on cortical responses. Furthermore, we identify that estrogen receptor alpha (ERα) is importantly expressed within the auditory cortex, displaying cell-type-specific expression patterns including enrichment in inhibitory neuron sub-populations. Further dissection of the molecular and cellular basis of estrogenic control of auditory cortical function will lay the foundation for understanding the organization of estrogenic signaling in the cortex.