Past events

The architecture of the primate visual system is based on the fovea-fixation-saccade system for high-acuity vision. This talk will describe an analogous system in night vision of monkeys. Processing is based not on the fovea but on a ‘scotopic center’. Unlike the fovea, which is fixed in the retina, the scotopic center relocates over a ‘scotopic band’, according to the intensity of the ambient light and, more generally, perceptual uncertainty. The eye movements involved have sensorimotor transformations specific to night vision. The discussion will touch on the evolution of vision, including relevance for humans. Link: https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421  

To unravel the functional properties of the brain, we need to untangle how neurons interact with each other and coordinate in large-scale recurrent networks. One way to address this question is to measure the functional influence of individual neurons on each other by perturbing them in vivo. Application of such single-neuron perturbations in mouse visual cortex has recently revealed feature- specific suppression between excitatory neurons, despite the presence of highly specific excitatory connectivity, which was deemed to underlie feature-specific amplification. Here, we studied which connectivity profiles are consistent with these seemingly contradictory observations, by modeling the effect of single-neuron perturbations in large-scale neuronal networks. Our numerical simulations and mathematical analysis revealed that, contrary to the prima facie assumption, neither inhibition dominance nor broad inhibition alone were sufficient to explain the experimental findings; instead, strong and functionally specific excitatory–inhibitory connectivity was necessary, consistent with recent findings in the primary visual cortex of rodents. Such networks had a higher capacity to encode and decode natural images, and this was accompanied by the emergence of response gain nonlinearities at the population level. Our study provides a general computational framework to investigate how single-neuron perturbations are linked to cortical connectivity and sensory coding and paves the road to map the perturbome of neuronal networks in future studies. Zoom Link: https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421

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. 

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 Physical activity plays a vital role in maintaining a healthy brain, augmenting memory and cognition in both humans and animals. Previous studies have identified multiple distinct molecular and cellular factors that mediate these effects, both within the brain and systemically. However, what remains unknown is how exercise affects the neural coding mechanisms that underlie these cognitive and memory abilities. In my work I addressed this question in the context of spatial cognition, and studied how chronic voluntary exercise affects the quality and the long-term stability of hippocampal place codes. I performed longitudinal imaging of calcium activity in the hippocampal CA1 of mice as they repeatedly explored initially novel environments over weeks, and compared the place codes of mice that voluntarily ran on wheels in their home cage to those of sedentary mice. As previously reported, physical activity enhanced adult neurogenesis rates in the hippocampal dentate gyrus in the running group. I found that running increased the firing rates and the information content that place cells carry about position. In addition, I discovered a surprising relationship between physical activity and long-term neural-code stability: although running mice demonstrated an overall more stable place code than sedentary mice, their place code exhibited a higher degree of representational drift when controlling for code quality level. Using a simulated neural network, I found that the combination of both improved code quality and faster representational drift in runners, but neither of these effects alone, could recapitulate my experimental results. Overall, these results imply a role for physical activity in both improving the spatial code and accelerating representational drift in the hippocampus. Zoom link-https://weizmann.zoom.us/j/93585241611?pwd=RGsxakU2aElVQ01nbUpuRjVqOWQ0QT09 Meeting ID: 935 8524 1611 Password: 243908

Depression and anxiety disorders are among the most common childhood psychiatric disorders. Selective serotonin reuptake inhibitors (SSRIs) are generally considered first-line treatment for both depression and anxiety in this age group. However, 30%–40% of all patients who receive a sufficient dose and duration of treatment fail to respond. Moreover, SSRI use is frequently associated with adverse events (AEs), including activation symptoms, manic switch and increased suicidal behavior (SBs). These are particularly relevant in pediatric populations because of concerns about the suicide threat of SSRIs, resulting in a "black-box" warning. There are currently no biomarkers that can predict treatment response or AEs. Identification of such biomarkers could help to maximize the benefit-risk ratio for the use of SSRIs and speed the matching of treatment to patient. Given the fact that depression / anxiety risk is influenced by both genetic and environmental factors and that both state and trait factors will be important in treatment response prediction, a multidimensional biomarker panel covering several levels of biological information would likely be necessary. The main objective of this research thesis is to identify biomarkers that will aid in the prediction of response and suicidal and other AEs of SSRI treatment in children and adolescents treated for depression and/or anxiety disorders. We examined the involvement of specific biomarkers (miRNA’s, DNA methylation, single nucleotide polymorphism [SNP's] and metabolites) in the response to SSRIs treatment in children and adolescents and in the differences observed between individuals exhibiting response or non-response/AEs to treatment with SSRIs. Two hundred and sixty-six children and adolescents with depression and/or anxiety disorders were recruited and treated with fluoxetine. The overall response rate was 55%. Several targets from several biological domains (DNA methylation profile, miRNA’s and metabolites) were identifies as differentially expressed between responders and non-responders at baseline test. Pathway analysis of the predicted targets was carried out to assess their putative biological functions. Interestingly, when combining targets from the four biological domains, the targets were predicted to regulate specific biological pathways associated with immune system pathways and/or developmental pathways. Dysregulation of complex gene networks in the developing brain is thought to underlie depression with childhood or adolescent onset. Thus, the identified molecules might play critical roles in transcriptional networks related to treatment response and AEs. These transcriptional networks are particularly relevant to the developing human brain and to neurodevelopmental disorders with childhood/adolescent onset, such as depression and anxiety disorders. Zoom link: https://weizmann.zoom.us/j/91093085114?pwd=RVBKbEZXbjlsaVZrUVRuNThtVHB1UT09 Meeting ID: 910 9308 5114 Password : 419366

Dopamine regulates multiple brain functions including learning, motivation and movement. Furthermore, the striatum, a major target of dopamine neurons, is parceled into multiple subregions that are associated with different types of behavior, such as Pavlovian, goal-directed, and habitual behaviors. An important question in the field is how dopamine regulates these diverse functions. It has been thought that midbrain dopamine neurons broadcast reward prediction error signals to drive reinforcement learning. However, recent studies have found more diverse dopamine signals than originally thought. How can we reconcile these results? In this talk, I will discuss our recent studies characterizing diverse dopamine signals, and how these findings can be understood in a coherent theoretical framework. Zoom Link: https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421