Graphical AbstractHighlights d Fast-spiking interneurons are strongly activated with social facial touch in rats d Fast-spiking neuron firing is regulated by the estrus cycle and estrogen d Esr2 is expressed in cortical parvalbumin neurons and is regulated by estrus d Excitability of PV neurons is mediated by an estrogen receptor b (Esr2) mechanism Correspondence michael.brecht@bccn-berlin.de In BriefClemens et al. perform in vivo and in vitro electrophysiology in barrel cortex of female rats. Fast-spiking neurons are strongly activated with social touch and vary their firing with the estrus cycle and estradiol. Estrogen acts locally to increase cortical fast-spiking neuron excitability with an estrogen receptor b (Esr2) mechanism. SUMMARYFemale mammals experience cyclical changes in sexual receptivity known as the estrus cycle. Little is known about how estrus affects the cortex, although alterations in sensation, cognition and the cyclical occurrence of epilepsy suggest brain-wide processing changes. We performed in vivo juxtacellular and whole-cell recordings in somatosensory cortex of female rats and found that the estrus cycle potently altered cortical inhibition. Fast-spiking interneurons were strongly activated with social facial touch and varied their ongoing activity with the estrus cycle and estradiol in ovariectomized females, while regular-spiking excitatory neurons did not change. In situ hybridization for estrogen receptor b (Esr2) showed co-localization with parvalbuminpositive (PV + ) interneurons in deep cortical layers, mirroring the laminar distribution of our physiological findings. The fraction of neurons positive for estrogen receptor b (Esr2) and PV co-localization (Esr2 + PV + ) in cortical layer V was increased in proestrus. In vivo and in vitro experiments confirmed that estrogen acts locally to increase fast-spiking interneuron excitability through an estrogen-receptorb-dependent mechanism.

Female mammals experience cyclical changes in sexual receptivity known as the estrus-cycle. Little is known about how estrus affects the cortex although alterations in sensation, cognition and the cyclic occurrence of epilepsy suggest brain-wide processing changes. We performed in vivo juxtacellular and whole-cell recordings in somatosensory cortex of female rats and found that the estrus-cycle potently altered cortical inhibition. Fast-spiking interneurons strongly varied their activity with the estrus-cycle and estradiol in ovariectomized females, while regular-spiking excitatory neurons did not change. In vivo whole-cell recordings revealed a varying excitation-to-inhibition-ratio with estrus. In situ hybridization for estrogen receptor β (Esr2) showed co-localization with parvalbumin-positive interneurons in deep cortical layers, mirroring the laminar distribution of our physiological findings. In vivo and in vitro experiments confirmed that estrogen acts locally to increase fastspiking interneuron excitability through an estrogen receptor β mechanism. We conclude that sex hormones powerfully modulate cortical inhibition in the female brain.Clemens et al.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding the influence of mutations in the SARS-CoV-2 gene on clinical outcomes is critical for treatment and prevention. Here, we analyzed all high-coverage complete SARS-CoV-2 sequences from GISAID database from January 1, 2020, to January 1, 2021, to mine the mutation hotspots associated with clinical outcome and developed a model to predict the clinical outcome in different epidemic strains. Exploring the cause of mutation based on RNA-dependent RNA polymerase (RdRp) and RNA-editing enzyme, mutation was more likely to occur in severe and mild cases than in asymptomatic cases, especially A > G, C > T, and G > A mutations. The mutations associated with asymptomatic outcome were mainly in open reading frame 1ab (ORF1ab) and N genes; especially R6997P and V30L mutations occurred together and were correlated with asymptomatic outcome with high prevalence. D614G, Q57H, and S194L mutations were correlated with mild and severe outcome with high prevalence. Interestingly, the single-nucleotide variant (SNV) frequency was higher with high percentage of nt14408 mutation in RdRp in severe cases. The expression of ADAR and APOBEC was associated with clinical outcome. The model has shown that the asymptomatic percentage has increased over time, while there is high symptomatic percentage in Alpha, Beta, and Gamma. These findings suggest that mutation in the SARS-CoV-2 genome may have a direct association with clinical outcomes and pandemic. Our result and model are helpful to predict the prevalence of epidemic strains and to further study the mechanism of mutation causing severe disease.