Publications

Correction to: Scientific Reports, published on 16 August 2023 In the original version of this Article, Tali Kimchi was omitted as a corresponding author. Correspondence and requests for materials should also be addressed to tali.kimchi@weizmann.ac.il Also, The Funding section in the original version of this Article was omitted. The Funding section now reads: “Support from the Minerva Foundation (Germany), the Israel Science Foundation (grants 3594/21, 2141/21 and 1874/22) and the Perlman Family Foundation, are gratefully acknowledged. OC is the recipient from an Israel Ministry of Absorption fellowship. LF holds the Bertha and Isadore Gudelsky Professorial Chair and Heads the Clore Institute for High-Field Magnetic Resonance Imaging and Spectroscopy (Weizmann Institute) whose support is also acknowledged” The original Article has been corrected.

Ultraviolet (UV) light affects endocrinological and behavioral aspects of sexuality via an unknown mechanism. Here we discover that ultraviolet B (UVB) exposure enhances the levels of sex-steroid hormones and sexual behavior, which are mediated by the skin. In female mice, UVB exposure increases hypothalamus-pituitary-gonadal axis hormone levels, resulting in larger ovaries; extends estrus days; and increases anti-Mullerian hormone (AMH) expression. UVB exposure also enhances the sexual responsiveness and attractiveness of females and male-female interactions. Conditional knockout of p53 specifically in skin keratinocytes abolishes the effects of UVB. Thus, UVB triggers a skin-brain-gonadal axis through skin p53 activation. In humans, solar exposure enhances romantic passion in both genders and aggressiveness in men, as seen in analysis of individual questionaries, and positively correlates with testosterone level. Our findings suggest opportunities for treatment of sex-steroid-related dysfunctions.

Microglia, the brain-resident immune cells, are critically involved in many physiological and pathological brain processes, including neurodegeneration. Here we characterize microglia morphology and transcriptional programs across ten species spanning more than 450 million years of evolution. We find that microglia express a conserved core gene program of orthologous genes from rodents to humans, including ligands and receptors associated with interactions between glia and neurons. In most species, microglia show a single dominant transcriptional state, whereas human microglia display significant heterogeneity. In addition, we observed notable differences in several gene modules of rodents compared with primate microglia, including complement, phagocytic, and susceptibility genes to neurodegeneration, such as Alzheimer's and Parkinson's disease. Our study provides an essential resource of conserved and divergent microglia pathways across evolution, with important implications for future development of microglia-based therapies in humans.

This interesting study from the Bartolomucci lab provides a new insight on the long-term impact of social stress, specifically stemming from the individual ranking in a dominance hierarchy.

Assigning the appropriate animal model for the scientific question, rather than adapting the scientific question to the available/convenient animal model.

Female-emitted pheromonal inputs possess an intrinsic rewarding value for conspecific males, promoting approach and investigation of the potential mating partner. In mice these inputs are detected mainly by the vomeronasal organ (VNO) and the main olfactory epithelium (MOE). We investigated the role of VNO-mediated inputs in experience-dependent plasticity of reproductive responses. We applied a sex-specific conditioned odor aversion (COA) paradigm on adult, wild-type (WT) male mice and on male mice impaired in VNO-mediated signal transduction (TrpC2^−/−). We found that WT males, which underwent COA to female-soiled bedding, lost their innate preference to female odors and presented lower motivation to approach a sexually receptive female. COA also abolished the testosterone surge normally seen following exposure to female odors. Moreover, the conditioned males displayed impairments in copulatory behaviors, which lasted for several weeks. Surprisingly, these males also exhibited phobic behaviors towards receptive females, including freezing and fleeing responses. In contrast, WT males which underwent COA specifically to male pheromones showed no change in olfactory preference and only a marginally significant elevation in intermale aggression. Finally, we show that TrpC2^−/− males were able to acquire aversion to female-soiled bedding and presented similar behavioral alterations following COA in their responses to female cues. Our results demonstrate that the intrinsic rewarding value of female pheromones can be overridden through associative olfactory learning, which occurs independently of VNO inputs, probably through MOE signaling.

It is commonly assumed, but has rarely been demonstrated, that sex differences in behaviour arise from sexual dimorphism in the underlying neural circuits. Parental care is a complex stereotypic behaviour towards offspring that is shared by numerous species. Mice display profound sex differences in offspring-directed behaviours. At their first encounter, virgin females behave maternally towards alien pups while males will usually ignore the pups or attack them. Here we show that tyrosine hydroxylase (TH)-expressing neurons in the anteroventral periventricular nucleus (AVPV) of the mouse hypothalamus are more numerous in mothers than in virgin females and males, and govern parental behaviours in a sex-specific manner. In females, ablating the AVPV TH⁺ neurons impairs maternal behaviour whereas optogenetic stimulation or increased TH expression in these cells enhance maternal care. In males, however, this same neuronal cluster has no effect on parental care but rather suppresses inter-male aggression. Furthermore, optogenetic activation or increased TH expression in the AVPV TH⁺ neurons of female mice increases circulating oxytocin, whereas their ablation reduces oxytocin levels. Finally, we show that AVPV TH⁺ neurons relay a monosynaptic input to oxytocin-expressing neurons in the paraventricular nucleus. Our findings uncover a previously unknown role for this neuronal population in the control of maternal care and oxytocin secretion, and provide evidence for a causal relationship between sexual dimorphism in the adult brain and sex differences in parental behaviour.

All species perceive sensory stimuli from the environment through dedicated sensory modalities, and respond with appropriate behaviours designed to maximize fitness and reproductive success. In most mammalian species, information regarding sex, age and other species-specific social and reproductive characteristics is conveyed by pheromones, which are detected by the vomeronasal and olfactory systems. Traditionally, pheromone signals have been thought to possess intrinsic rewarding meanings and to trigger 'innate' hardwired social behavioural responses. In contrast, odorants are considered to possess mostly neutral reward value, but may induce approach or avoidance behaviours as a result of experience or through conditioning following pairing with stimuli that possess intrinsic rewarding properties. This review describes studies demonstrating that innate behavioural responses, with particular emphasis on reproductive responses mediated by pheromonal signals, are actually flexible and substantially influenced by past experience and associative learning. These attributes allow the animal to assign new motivational incentives to pheromones associated with social and reproductive behaviours, thus providing adaptive ability to cope with unique changes in internal and external environmental conditions. We argue that responses to pheromones are far more easily modified by experience than would be expected from hardwired innate responses, and that the behaviours they elicit are chiefly plastic and sensitive to modification throughout life by sensory-mediated emotional experience.

From invertebrates to humans, males and females of a given species display identifiable differences in behaviors, mostly but not exclusively pertaining to sexual and social behaviors. Within a species, individuals preferentially exhibit the set of behaviors that is typical of their sex. These behaviors include a wide range of coordinated and genetically pre-programmed social and sexual displays that ensure successful reproductive strategies and the survival of the species. What are the mechanisms underlying sex-specific brain function? Although sexually dimorphic behaviors represent the most extreme examples of behavioral variability within a species, the basic principles underlying the sex specificity of brain activity are largely unknown. Moreover, with few exceptions, the quest for fundamental differences in male and female brain structures and circuits that would parallel that of sexual behaviors and peripheral organs has so far uncovered modest quantitative rather than the expected clear qualitative differences. As will be detailed in this review, recent advances have directly challenged the established notion of the unique role of steroid hormones in organizing and activating male- and female-specific brain circuits and have uncovered new mechanisms underlying the neural control of sex-specific behaviors.

We compared the role of tactile perception in maze learning in the blind mole rat and in the laboratory rat. Both species were tested in each of two mazes that were identical in complexity but differed in tunnel width and height: the first was only slightly wider than the animal's body width (narrow maze) while the second was about twice the animal's body width (wide maze). We found that the performances of rats tested in the narrow maze were significantly lower than those tested in the wide maze, as measured by time and number of errors to reach the end of the maze (food reward). The mole rats, in contrast, performed significantly better in the narrow maze than in the wide maze. Further, in contrast to the rats, the mole rats' locomotion in the wide maze was much less continuous than in the narrow maze, reflected in longer and more frequent stops at maze junctions, where they pressed the side of their body tightly against the tunnel walls. Two main conclusions are derived from this experiment. First, subterranean mammals, such as the blind mole rat, appear to rely more on tactile stimuli while exploring and learning a complex maze than do sighted surface-dwelling rodents, such as rat. The extensive use of this somatosensory channel may compensate for the mole rats' visual deficiency, and thus substantially contribute to their excellent spatial orientation ability, previously demonstrated in field and laboratory conditions. Second, poor performance of surface-dwelling rodents, such as the rats, in spatial-maze learning tasks might not be a consequence of impaired cognitive learning ability, but rather due to testing the animal in a physical situation that does not provide the necessary somatosensory stimuli found in their natural habitat.

Orientation by an animal inhabiting an underground environment must be extremely efficient if it is to contend effectively with the high energetic costs of excavating soil for a tunnel system. We examined, in the field, the ability of a fossorial rodent, the blind mole-rat, Spalax ehrenbergi, to detour different types of obstacles blocking its tunnel and rejoin the disconnected tunnel section. To create obstacles, we dug ditches, which we either left open or filled with stone or wood. Most (77%) mole-rats reconnected the two parts of their tunnel and accurately returned to their orginal path by digging a parallel bypass tunnel around the obstacle at a distance of 10-20 cm from the open ditch boundaries or 3-8 cm from the filled ditch boundaries. When the ditch was placed asymmetrically across the tunnel, the mole-rats detoured around the shorter side. These findings demonstrate that mole-rats seem to be able to assess the nature of an obstacle ahead and their own distance from the obstacle boundaries, as well as the relative location of the far section of disconnected tunnel. We suggest that mole-rats mainly use reverberating self-produced seismic vibrations as a mechanism to determine the size, nature and location of the obstacle, as well as internal self-generated references to determine their location relative to the disconnected tunnel section.

Studies dealing with spatial orientation in mammals have mostly dealt with surface-dwelling species. We studied the ability of a subterranean rodent to orient in space and compared it with two species of rodents that spend most of their lives above ground. The solitary blind mole-rat, Spalax ehrenbergi, inhabits an extensive, branching tunnel system that it digs itself and in which it spends its entire life. We examined its ability to learn and remember a winding path towards a goal in a multiple labyrinth and compared it with Levant voles, Microtus guentheri, and laboratory rats, Rattus norvegicus. The mole-rats learned significantly faster than the rats and voles. Furthermore, their ability to remember the maze was significantly better than that of the rats after 2, 7, 30 and 60 days from the end of the learning experiment and significantly better than the voles after 120 days. The mole-rats still retained ca. 45% of their optimal performance at the end of the learning experiment after 4 months compared with 20% for the voles after 4 months and less than 20% for the rats after 2 months. Despite having lost its vision, the mole-rat was thus more able to orient in a complex maze than the surface-dwelling vole and laboratory rat. We suggest that the mole-rat compensates for the sensory limitations imposed by the subterranean niche and for its loss of vision by relying on the Earth's magnetic field and internal cues to steer its course efficiently. We discuss the possible mechanisms of orientation.