לוח שנה משולב

Aggression and dominance hierarchy are basic social behaviors that are essential for the survival and reproductive success of most mammalian species. Typically, they are displayed whenever conspecifics have to compete for limited resources, such as food, water, territory, or access to mates. As a result, and due to sexual selection, intra-sexual competition is higher in males compared to females as fertile females are a limited resource to males. Thus, males often express a higher level of aggression and are most likely to form a dominance hierarchy in a group. Therefore, most studies of the biological basis of intra-sexual aggression and dominance hierarchy have been focused on males. However, it has long been observed that females also compete with each other and can form dominant hierarchies.
In this study, we aimed to investigate the role of OT+ PVN neurons in the aggression of wild-derived female mice by comparing them to males. Wild-derived mice were chosen for their higher levels of aggression compared to the lab mouse strains, which might have lost these behavioral traits due to artificial selection and socially restricted environment while in captivity.
To manipulate OT+ PVN neurons, we established a wild OT:Cre mouse line by backcrossing wild-derived mice with transgenic lab mice and validated that its phenotype resembles the wild-derived mice. Using these novel wild-backcrossed OT:Cre (Wild-BX) mice, we found that OT+ PVN neurons of females are activated due to agonistic interaction.
Next, we virally ablated, using Casp3, or activated, using DREADD, OT+ PVN neurons in wild-BX males and females, and performed a standard resident-intruder assay (RI) to examine territorial aggression towards same-sex adults and unfamiliar pups. We found that ablation of OT+ PVN neurons in wild-BX females reduces adult and pup-directed aggression and increases sniffing behavior. In contrast, activation of this neuronal population promotes aggressive behavior toward adults and pups and decrees sniffing behavior. In males, similar manipulations did not affect either of these aggressive or sniffing behaviors, except a weak impact on pup-directed aggression.
Moreover, by examining group behavior in a semi-natural environment, we found that ablation of OT+ PVN neurons suppresses dominant hierarchy formation in groups of wild-BX females. In contrast, activation strengthened the hierarchy and increased agonistic behavior in the group. In males, in contrast to the RI, the OT+ PVN ablation delayed the formation of the hierarchy and increased the anxiety in the group, whereas activation weakened the hierarchy and increased pro-social behavior.
These findings suggest that OT PVN neurons have a sexually-dimorphic effect in aggression and dominance hierarchy behaviors, and they emphasize the importance of investigating both sexes in ethologically-relevant animal models and social contexts, in the study of socially relevant neuromodulators.

Zoom link: https://weizmann.zoom.us/j/96648920836?pwd=OXlvV0NPTHIrVHNLYUpvZ2lNTnJZdz09
Meeting ID: 966 4892 0836
Password: 248477

Abstract:

Evolution is driven by random mutations, whose fitness outcome is tested over time. In vitro evolution of a library of a randomly mutated protein mimics this process, however, on a short time-scale, driven by a specific outcome (such as binding to a bait). Here, we used directed in vitro evolution to investigate the role of molecular chaperones in curbing promiscuity in favor of specificity of protein-protein interactions. Using yeast surface display, we generated a random library of the E. coli protein Uracil glycosylase (UNG), and selected it against various baits. Those included the purified chaperones GroEL, DnaK+DnaJ+ATP, or total protein extracts from WT or delta DnaK+DnaJ cells. We show that in-vitro evolution differs from natural evolution in cells, both physically and thermodynamically. We found that chaperones, whether purified or as ! part of the protein-extract, select for, and thus enrich uracil glycosylase (UNG) misfolded species during this in vitro evolution process. In a more general context, our results show that chaperones purge promiscuous misfolded clones from the system, and thereby avoiding their detrimental effects, such as forming wrong interactions with other macromolecules, including proteins, which can harm proteostasis.

Navigation, the ability to reach a desired goal location, is a complex behavior that occurs in complex environments. It requires the animal to know its own location in the environment, but also be attentive to other things in the environment that could influence its route – such as the navigational goal or other alternative goals, landmarks and obstacles along the route, as well as other conspecifics it may encounter. Despite the complexity and richness of real-world navigation, most studies of the neural basis of navigation were done in small empty setups. During my PhD, I focused on how the hippocampus represents navigation in more naturalistic and dynamic scenarios. In my first PhD project I found a vectorial representation of spatial goals in the bat hippocampus, which could support goal-directed navigation. In my second PhD project I found that during dynamic ‘cross-overs’ between two bats, hippocampal neurons switched from representing the bat’s self-position to a conjunctive representation of position × distance to the other bat – an extremely rapid neuronal switch. Taken together, in my PhD I studied the neural basis of dynamic natural navigation by adding more naturalistic aspects of navigation – such as navigation to goals and collision-avoidance behavior – and this allowed me to reveal interesting and surprising new representations in the hippocampus.