Sex-specific topology of the nociceptive circuit shapes dimorphic behavior in C. elegans

How sexually dimorphic behavior is encoded in the nervous system is poorly understood. Here, we characterize the dimorphic nociceptive behavior in C. elegans and study the underlying circuits, which are composed of the same neurons but are wired differently. We show that while sensory transduction is similar in the two sexes, the downstream network topology markedly shapes behavior. We fit a network model that replicates the observed dimorphic behavior in response to external stimuli, and use it to predict simple network rewirings that would switch the behavior between the sexes. We then show experimentally that these subtle synaptic rewirings indeed flip behavior. Strikingly, when presented with aversive cues, rewired males were compromised in finding mating partners, suggesting that network topologies that enable efficient avoidance of noxious cues have a reproductive "cost". Our results present a deconstruction of the design of a neural circuit that controls sexual behavior, and how to reprogram it.

Sex differences in vocalizations to familiar or unfamiliar females in mice

Mice, both wild and laboratory strains, emit ultrasound to communicate. The sex differences between male to female (male–female) and female to female (female– female) ultrasonic vocalizations (USVs) have been discussed for decades. In the present study, we compared the number of USVs emitted to familiar and unfamiliar females by both males (male–female USVs) and females (female–female USVs). We found that females vocalized more to unfamiliar than to familiar females. In contrast, males exhibited more USVs to familiar partners. This sexually dimorphic behavior suggests that mice change their vocal behavior in response to the social context, and their perception of the context is based on social cognition and memory. In addition, because males vocalized more to familiar females, USVs appear to be not just a response to novel things or individuals, but also to be a social response.

Rapid acclimation of the cortisol stress response in adult turquoise killifish Nothobranchius furzeri

The turquoise killifish Nothobranchius furzeri is an increasingly popular model species for comparative vertebrate research, and the basic physiology including responses to stressful stimuli are of primary interest. We exposed adult killifish to a single or repeated periods of acute confinement followed by analysis of tissue cortisol and plasma cortisol concentrations. Individuals were also sampled for messenger RNA (mRNA) expression of corticotropin-releasing hormone ( CRH), mineralocorticoid receptor ( MR), and glucocorticoid receptor ( GR) in the brain to examine the effects of repeated stress events on constitutive expression of these important stress axis components. Following a single 30-minute confinement stress, male plasma cortisol significantly differed from baseline ( p = 0.04). Both male and female whole-body cortisol were significantly increased ( p = 0.004 and p = 0.04, respectively) at 15 and 30 minutes poststress. Despite obvious dimorphic behavior and morphology, cortisol concentrations did not differ between the sexes. Exposure to daily repeated confinement for one week altered the cortisol response in both sexes. Time 0, 15, and 60 minutes poststress cortisol concentrations were depressed in repeatedly stressed males ( p ≤ 0.05), and times 0, 30 and 120 minutes poststress cortisol concentrations were depressed in repeatedly stressed females ( p ≤ 0.05). Constitutive expression of CRH, MR, and GR mRNA in the brain following one week of repeated stress events did not differ among treatments or sexes. This study introduces the first description of hypothalamic-pituitary-interrenal axis activity in this important model species. Reduced cortisol production in repeatedly stressed adult killifish suggests acclimation to repeated stressors. Furthermore, acclimation was rapid, and plasma cortisol concentrations altered significantly in as little as one week.

Sex-specific regulation ofLgr3inDrosophilaneurons

The development of sexually dimorphic morphology and the potential for sexually dimorphic behavior inDrosophilaare regulated by the Fruitless (Fru) and Doublesex (Dsx) transcription factors. Several direct targets of Dsx have been identified, but direct Fru targets have not been definitively identified. We show thatDrosophilaleucine-rich repeat G protein-coupled receptor 3 (Lgr3) is regulated by Fru and Dsx in separate populations of neurons.Lgr3is a member of the relaxin-receptor family and a receptor for Dilp8, necessary for control of organ growth.Lgr3expression in the anterior central brain of males is inhibited by the B isoform of Fru, whose DNA binding domain interacts with a short region of anLgr3intron. Fru A and C isoform mutants had no observed effect onLgr3expression. The female form of Dsx (DsxF) separately up- and down-regulatesLgr3expression in distinct neurons in the abdominal ganglion through female- and male-specificLgr3enhancers. Excitation of neural activity in the DsxF–up-regulated abdominal ganglion neurons inhibits female receptivity, indicating the importance of these neurons for sexual behavior. Coordinated regulation ofLgr3by Fru and Dsx marks a point of convergence of the two branches of the sex-determination hierarchy.

Large-scale identification of proteins involved in the development of a sexually dimorphic behavior

Sexually dimorphic behaviors develop under the influence of sex steroids, which induce reversible changes in the underlying neural network of the brain. However, little is known about the proteins that mediate these activational effects of sex steroids. Here, we used a proteomics approach for large-scale identification of proteins involved in the development of a sexually dimorphic behavior, the electric organ discharge of brown ghost knifefish, Apteronotus leptorhynchus. In this weakly electric fish, the discharge frequency is controlled by the medullary pacemaker nucleus and is higher in males than in females. After lowering the discharge frequency by chronic administration of β-estradiol, 2-dimensional difference gel electrophoresis revealed 62 proteins spots in tissue samples from the pacemaker nucleus that exhibited significant changes in abundance of >1.5-fold. The 20 identified protein spots indicated, among others, a potential involvement of astrocytes in the establishment of the behavioral dimorphism. Indeed, immunohistochemical analysis demonstrated higher expression of the astrocytic marker protein GFAP and increased gap-junction coupling between astrocytes in females compared with males. We hypothesize that changes in the size of the glial syncytium, glial coupling, and/or number of glia-specific potassium channels lead to alterations in the firing frequency of the pacemaker nucleus via a mechanism mediating the uptake of extracellular potassium ions from the extracellular space.