Identification of midbrain neurons essential for vocal communication

Abstract

8Vocalizations are an essential medium for communication and courtship in numerous 9 mammalian species ranging from mice to humans. In mammals, the midbrain PAG serves as 10 an obligatory node in a vocalization-related network that spans the forebrain and brainstem 1-3 , 11as bilateral lesions of the PAG result in mutism 2-5 . Despite the PAG's importance for vocal 12 production, the identity, function, and connectivity of PAG neurons involved in vocalization has 13 remained elusive, in part because the PAG is a functionally and anatomically heterogeneous 14 structure that serves myriad roles including nociception, defensive behaviors, and autonomic 15 regulation 6-9 . Here we used a viral genetic "tagging" method 10,11 to identify a distinct subset of 16 PAG neurons in the male mouse that are selectively activated during the production of 17 ultrasonic vocalizations (USVs) elicited by female cues. Silencing these PAG-USV neurons 18 rendered males mute without affecting their other courtship behaviors and also impaired their 19 ability to attract female mice in a social choice assay. Activating these neurons using 20 chemogenetic or optogenetic methods strongly elevated USV production, even in the absence 21 of female cues. Notably, the timing of individual USVs was entrained to the expiratory phase of 22

Evaluating the landscape of gene cooperativity with receptor tyrosine kinases in liver tumorigenesis using transposon-mediated mutagenesis

“…The comparison we performed between the outcomes of SB transposon mutagenesis carried out in the present Alb-R26 Met genetic setting and in other settings[21, [31][32][33][34][35] revealed that among the 275 Alb-R26 Met -transposon genes, aside from a large group of common hits, 49 genes were only found in the Alb-R26 Met context, which we named 'putative RTK-specific genes'. For a proportion of them, it is possible that they could have been missed in previous screens because transposon mutagenesis does not reach saturation levels, particularly with small numbers of analysed tumours.…”

“…Next, we assessed the level of specificity in gene cooperation with enhanced MET levels by comparing the Alb-R26 Met -transposon genes with those identified in other liver SB screens: p53 mut [21]), Myc over [31], HBV tg [32], chemically induced chronic liver injury [33], hepatic steatosis [34], epithelial-mesenchymal transition [35]. Among the 275 Alb-R26 Met -transposon genes, 226 (82%) were found in one or more SB screen cohorts.…”