All events, All years

The impact of metabolic processes at the brain’s choroid plexus and of the gut microbiome on Alzheimer’s disease manifestation

Lecture
Date:
Thursday, March 24, 2022
Hour: 16:00
Location:
Afroditi Tsitsou-Kampeli
|
Prof. Michal Schwartz Lab Dept of Brain Sciences

The immune system and the gut microbiome are becoming major players in chronic neurodegenerative conditions. One of the key interfaces between the brain and the immune system with an impact on brain function is the choroid plexus (CP). The CP interface is central to the maintenance of brain homeostasis by exerting a plethora of different biological processes. However, in aging and Alzheimer’s disease (AD), interferon type-I (IFN-I) signaling accumulates at the CP and impedes part of its beneficial function by inducing a CP-pro-aging signature. My research contributed to the finding that IFN-I signaling at the CP induces an aging-like signature in microglia and impedes cognitive abilities in middle-aged mice in a microglia-dependent manner. In addition, I demonstrated that the brain-specific enzyme, cholesterol 24-hydroxylase (CYP46A1), is expressed by the CP epithelium and that its product, 24-hydroxycholesterol (24-OH), downregulates CP-pro-inflammatory signatures. Furthermore, in AD, CP CYP46A1 protein levels were decreased in both mice and humans and overexpression of Cyp46a1 at the CP in 5xFAD mice reversed brain inflammation, microglial dysfunction signatures, and cognitive loss. Finally, while the pro-inflammatory cytokine TNF-α impaired CP Cyp46a1 expression in vitro, boosting systemic immunity in vivo increased its levels in an IFNGR2-dependent manner. These results highlight CYP46A1 at the CP as a remote regulator of brain inflammation, which diminishes with neurodegeneration, but is amenable to rescue. Focusing on the gut microbiome, I found that 5xFAD mice devoid of microbiome exhibited a striking decrease of long-term spatial memory deficit and increased synaptic and neuronal survival. Spatial memory deficit in 5xFAD mice kept in germ free (GF) or specific-pathogen free (SPF) conditions, negatively correlated with the abundance of 2-hydroxypyridine, while systemic, chronic supply of 2-hydroxypyridine in SPF 5xFAD mice improved spatial memory deficits in comparison to phosphate-buffered saline (PBS)-supplied 5xFAD mice. Overall, these findings demonstrate a microbiome-dependent effect on AD pathology in the 5xFAD mouse model and suggest a connection between 2-hydroxypyridine and AD manifestation. In general, this research thesis addresses novel aspects of choroid plexus and gut microbiome metabolism and their relation to AD progression. Zoom link https://weizmann.zoom.us/j/98658552127?pwd=ZkZmWTBkd1AxZ0xPbGlpU3FPUWpzUT09 Meeting ID:986 5855 2127 Password:495213

Cracking the olfactory code using behavior

Lecture
Date:
Sunday, March 13, 2022
Hour: 10:00 - 11:00
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Dmitry Rinberg
|
Dept of Neuroscience and Physiology, NYU

Two of the most fundamental questions of sensory neuroscience are: 1) how is stimulus information represented by neuronal activity? and 2) what features of this activity are read out to guide behavior? The first question has been the subject of a large body of work across different sensory modalities. The second question remains a significant challenge, since one needs to establish a causal link between neuronal activity and behavior. In olfaction, it has been proposed that information about odors is encoded in spatial distribution of receptor activation and the next level mitral/tufted cells, as well as in their relative timing and synchrony. However, the role of different features of neural activity in guiding behavior remains unknown. Using mouse olfaction as a model system, we developed both technological and conceptual approaches to study sensory coding by perturbing neural activity at different levels of information processing during sensory driven behavioral tasks. We developed methods for both one-photon spatiotemporal pattern stimulation using digital mirror devices at the glomerulus level in the olfactory bulb, and two-photon holographic pattern stimulation deeper in the brain, at the level of mitral/tufted cells. Using these techniques, we performed quantitative behavioral experiments to, first, measure psychophysical limits of the readability of different features of the neural code, and, second, to quantify their behavioral relevance. Based on these results, we built a detailed mathematical model of the behavioral relevance of the different features of spatiotemporal neural activity. Our approach can be potentially generalized to other sensory systems. Link: https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421

Brain-computer interfaces for basic science

Lecture
Date:
Thursday, March 10, 2022
Hour: 12:30 - 13:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Byron Yu
|
Carnegie Mellon University, Pittsburgh

Abstract: Brain-computer interfaces (BCI) translate neural activity into movements of a computer cursor or robotic limb. BCIs are known for their ability to assist paralyzed patients. A lesser known, but increasingly important, use of BCIs is their ability to further our basic scientific understanding of brain function. In particular, BCIs are providing insights into the neural mechanisms underlying sensorimotor control that are currently difficult to obtain using limb movements. In this talk, I will demonstrate how a BCI can be leveraged to study how the brain learns. Specifically, I will address why learning some tasks is easier than others, as well as how populations of neurons change their activity in concert during learning. Brief bio: Byron Yu received the B.S. degree in Electrical Engineering and Computer Sciences from the University of California, Berkeley in 2001. He received the M.S. and Ph.D. degrees in Electrical Engineering in 2003 and 2007, respectively, from Stanford University. From 2007 to 2009, he was a postdoctoral fellow jointly in Electrical Engineering and Neuroscience at Stanford University and at the Gatsby Computational Neuroscience Unit, University College London. He then joined the faculty of Carnegie Mellon University in 2010, where he is a Professor in Electrical & Computer Engineering and Biomedical Engineering, and the Gerard G. Elia Career Development Professor. He is broadly interested in how large populations of neurons process information, from encoding sensory stimuli to driving motor actions. His group develops and applies novel statistical algorithms and uses brain-computer interfaces to study brain function. Link- https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421

Neural representation geometry: a mesoscale approach linking learning to complex behavior

Lecture
Date:
Monday, March 7, 2022
Hour: 14:00 - 15:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Stefano Recanatesi
|
University of Washington, Seattle

I will demonstrate how neural representation geometry may hold the key to linking animal behavior and learning to circuit mechanisms. We will proceed in three steps. 1) We will start by establishing a connection between the sequential dynamics of complex behavior and geometrical properties of neural representations. 2) We will then link these geometrical properties to underlying circuit components. Specifically, we will uncover connectivity mechanisms that allow the circuit to control the geometry of its representations. 3) Finally, we will investigate how key geometrical structures emerge, de novo, through learning. To answer this, we will analyze the learning of representations in feedforward and recurrent neural networks trained to perform predictive tasks using machine learning techniques. As a result, we will show how both learning mechanisms and behavioral demands shape the geometry of neural representations.

Looking at night vision

Lecture
Date:
Tuesday, March 1, 2022
Hour: 12:30
Location:
Prof. Shabtai Barash
|
Department of Brain Sciences, WIS

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  

Effects of physical exercise and adult neurogenesis on hippocampal neural codes

Lecture
Date:
Thursday, February 10, 2022
Hour: 09:00 - 10:00
Location:
Yoav Rechavi - PhD Thesis Defense on Zoom
|
Prof. Yaniv Ziv, Lab Department of Brain Sciences

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

Theory of neural perturbome

Lecture
Date:
Tuesday, February 1, 2022
Hour: 12:30
Location:
Prof. Claudia Clopath
|
Department of Bioengineering Imperial College London, UK

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

To be announced

Lecture
Date:
Tuesday, January 25, 2022
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Alex Borst
|
Max Planck

Hippocampal spatial representation during dynamic natural navigation

Lecture
Date:
Tuesday, January 25, 2022
Hour: 10:00 - 11:15
Location:
Ayelet Sare l- PhD Thesis Defense
|
Prof. Nachum Ulanovsky Lab Dept of Brain Sciences, WIS

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. 

Student Seminar on Zoom - PhD Thesis Defense by Maya Amitai

Lecture
Date:
Wednesday, January 19, 2022
Hour: 10:00 - 11:00
Location:
Maya Amitai, MD, PhD
|
Prof. Alon Chen Lab Dept of Brain Sciences,WIS

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

Pages

All events, All years

Cracking the olfactory code using behavior

Lecture
Date:
Sunday, March 13, 2022
Hour: 10:00 - 11:00
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Dmitry Rinberg
|
Dept of Neuroscience and Physiology, NYU

Two of the most fundamental questions of sensory neuroscience are: 1) how is stimulus information represented by neuronal activity? and 2) what features of this activity are read out to guide behavior? The first question has been the subject of a large body of work across different sensory modalities. The second question remains a significant challenge, since one needs to establish a causal link between neuronal activity and behavior. In olfaction, it has been proposed that information about odors is encoded in spatial distribution of receptor activation and the next level mitral/tufted cells, as well as in their relative timing and synchrony. However, the role of different features of neural activity in guiding behavior remains unknown. Using mouse olfaction as a model system, we developed both technological and conceptual approaches to study sensory coding by perturbing neural activity at different levels of information processing during sensory driven behavioral tasks. We developed methods for both one-photon spatiotemporal pattern stimulation using digital mirror devices at the glomerulus level in the olfactory bulb, and two-photon holographic pattern stimulation deeper in the brain, at the level of mitral/tufted cells. Using these techniques, we performed quantitative behavioral experiments to, first, measure psychophysical limits of the readability of different features of the neural code, and, second, to quantify their behavioral relevance. Based on these results, we built a detailed mathematical model of the behavioral relevance of the different features of spatiotemporal neural activity. Our approach can be potentially generalized to other sensory systems. Link: https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421

Brain-computer interfaces for basic science

Lecture
Date:
Thursday, March 10, 2022
Hour: 12:30 - 13:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Byron Yu
|
Carnegie Mellon University, Pittsburgh

Abstract: Brain-computer interfaces (BCI) translate neural activity into movements of a computer cursor or robotic limb. BCIs are known for their ability to assist paralyzed patients. A lesser known, but increasingly important, use of BCIs is their ability to further our basic scientific understanding of brain function. In particular, BCIs are providing insights into the neural mechanisms underlying sensorimotor control that are currently difficult to obtain using limb movements. In this talk, I will demonstrate how a BCI can be leveraged to study how the brain learns. Specifically, I will address why learning some tasks is easier than others, as well as how populations of neurons change their activity in concert during learning. Brief bio: Byron Yu received the B.S. degree in Electrical Engineering and Computer Sciences from the University of California, Berkeley in 2001. He received the M.S. and Ph.D. degrees in Electrical Engineering in 2003 and 2007, respectively, from Stanford University. From 2007 to 2009, he was a postdoctoral fellow jointly in Electrical Engineering and Neuroscience at Stanford University and at the Gatsby Computational Neuroscience Unit, University College London. He then joined the faculty of Carnegie Mellon University in 2010, where he is a Professor in Electrical & Computer Engineering and Biomedical Engineering, and the Gerard G. Elia Career Development Professor. He is broadly interested in how large populations of neurons process information, from encoding sensory stimuli to driving motor actions. His group develops and applies novel statistical algorithms and uses brain-computer interfaces to study brain function. Link- https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421

Neural representation geometry: a mesoscale approach linking learning to complex behavior

Lecture
Date:
Monday, March 7, 2022
Hour: 14:00 - 15:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Stefano Recanatesi
|
University of Washington, Seattle

I will demonstrate how neural representation geometry may hold the key to linking animal behavior and learning to circuit mechanisms. We will proceed in three steps. 1) We will start by establishing a connection between the sequential dynamics of complex behavior and geometrical properties of neural representations. 2) We will then link these geometrical properties to underlying circuit components. Specifically, we will uncover connectivity mechanisms that allow the circuit to control the geometry of its representations. 3) Finally, we will investigate how key geometrical structures emerge, de novo, through learning. To answer this, we will analyze the learning of representations in feedforward and recurrent neural networks trained to perform predictive tasks using machine learning techniques. As a result, we will show how both learning mechanisms and behavioral demands shape the geometry of neural representations.

Looking at night vision

Lecture
Date:
Tuesday, March 1, 2022
Hour: 12:30
Location:
Prof. Shabtai Barash
|
Department of Brain Sciences, WIS

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  

Effects of physical exercise and adult neurogenesis on hippocampal neural codes

Lecture
Date:
Thursday, February 10, 2022
Hour: 09:00 - 10:00
Location:
Yoav Rechavi - PhD Thesis Defense on Zoom
|
Prof. Yaniv Ziv, Lab Department of Brain Sciences

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

Theory of neural perturbome

Lecture
Date:
Tuesday, February 1, 2022
Hour: 12:30
Location:
Prof. Claudia Clopath
|
Department of Bioengineering Imperial College London, UK

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

To be announced

Lecture
Date:
Tuesday, January 25, 2022
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Alex Borst
|
Max Planck

Hippocampal spatial representation during dynamic natural navigation

Lecture
Date:
Tuesday, January 25, 2022
Hour: 10:00 - 11:15
Location:
Ayelet Sare l- PhD Thesis Defense
|
Prof. Nachum Ulanovsky Lab Dept of Brain Sciences, WIS

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. 

Student Seminar on Zoom - PhD Thesis Defense by Maya Amitai

Lecture
Date:
Wednesday, January 19, 2022
Hour: 10:00 - 11:00
Location:
Maya Amitai, MD, PhD
|
Prof. Alon Chen Lab Dept of Brain Sciences,WIS

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

OT+ PVN neurons regulate aggression and dominance hierarchy in wild-derived female mice

Lecture
Date:
Thursday, January 13, 2022
Hour: 12:00 - 13:00
Location:
Itsik Sofer- Phd Thesis Defense
|
Prof. Tali Kimchi, Lab Dept of Brain Sciences, WIS

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

Pages

All events, All years

There are no events to display

All events, All years

There are no events to display

Pages