All events, All years

Deciphering non-neuronal cells contribution to Alzheimer’s disease pathology using high throughput transcriptomic and proteomic methods

Lecture
Date:
Wednesday, November 30, 2022
Hour: 14:00 - 15:00
Location:
Dept of Brain Sciences,Dr. Michal Schwartz,Sedi Medina (PhD Thesis Defense Seminar) on Zoom

Alzheimer's disease (AD) is a devastating pathology of the central nervous system (CNS) of unknown etiology which represents the most common neurodegenerative disorder. For decades, AD was perceived as a disease of the neuron alone. However, research advances in recent years have challenged this concept and shed light on the critical roles of non-neuronal cells on the development and progression of AD. In my PhD, I focused on understanding how two non-neuronal cell types - the Astrocytes and Microglia - respond to AD and how they possibly affect pathological processes. Our research identified a unique population of Astrocytes that significantly increased in association with brain pathology, which we termed disease-associated astrocytes (DAAs). This novel population of DAAs appeared at an early disease stage, increased in abundance with disease progression, and was not observed in young or in healthy adult animals. In addition, similar astrocytes appeared in aged wild-type (WT) mice and in aging human brains, suggesting their linkage to genetic and age-related factors. Aging is considered the greatest risk factor for AD, although the mechanism underlying the aging-related susceptibility to AD is unknown. One emerging factor that is involved in biological aging is the accumulation of senescent cells. Cellular senescence is a process in which aging cells change their characteristic phenotype. Under physiological conditions senescent cells can be removed by the immune system, however with aging, senescent cells accumulate in tissues, either due to a failure of effective removal or due to the accelerated formation of senescent cells. Our data highlight the contribution of non neuronal cells to AD pathogenesis by demonstrating  that 1. Overexpression of a specific gene by astrocytes affected the microglia cells' state, leading to a more homeostatic and less reactive microglial phenotype in comparison to the control group. 2. Accumulation of senescent microglia cells was observed in the brain of aged WT mice and AD mouse model (5xFAD), and by applying different therapeutic strategies we managed to observe significant quantitative differences in these cells, followed by a cognitive amelioration.

Organization of long-term behavior and individuality across developmental timescales

Lecture
Date:
Tuesday, November 29, 2022
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Shay Stern
|
Faculty of Biology TECHNION Haifa

Animals generate complex patterns of behavior across life that can be modified over days, months, or even years. Across these long timescales individuals within the same population may show stereotyped behaviors, but also unique behaviors that distinguish them from each other. How are long-term patterns of behavior organized and regulated across development? And what are the underlying processes that establish and modify individual-to-individual behavioral variation? By utilizing parallel long-term behavioral monitoring at high spatiotemporal resolution of multiple C. elegans individuals across their complete development time we demonstrate temporal regulation of behavioral plasticity by neuromodulators across developmental stages, structuring shared and unique individual responses to early-life experiences. I will further describe our development of unsupervised analyses of individual biases across development based on locomotion trajectory and individual postures which uncovered a large spectrum of individuality types within the isogenic populations. Lastly, I will present preliminary results suggesting that specific neuronal pathways are required to robustly synchronize long-term behavior with development time.

Molecular maps for odor processing in the mouse olfactory system

Lecture
Date:
Tuesday, November 22, 2022
Hour: 12:30 - 13:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Alexander Fleischmann
|
Brown University, Providence, USA

We are interested in the organization and function of neural circuits for sensory processing and behavior. A main goal of the lab is to integrate complementary approaches of system interrogation: we study the molecular diversity of cell types, their connectivity and functional properties; we investigate network dynamics and core computational principles; and we explore how learning and experience shapes behavioral decisions. I will discuss ongoing work aimed at characterizing molecular maps for odor processing in the mouse olfactory bulb. I will present preliminary data using spatial transcriptomics to generate a comprehensive map of glomerular identity and domain structure of the olfactory bulb. Furthermore, I will discuss single cell sequencing experiments and gene regulatory network models that define the diversity and connectivity of olfactory bulb projection neurons. I will try to illustrate how the early olfactory system of mice provides an ideal model system to integrate molecular biology, functional imaging, and behavioral experiments to address fundamental questions in sensory processing and behavior.

Skeletal muscle differentiation and fusion across scales

Lecture
Date:
Wednesday, November 9, 2022
Hour: 10:00 - 11:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Ori Avinoam
|
Dept of Biomolecular Sciences

Selective vascular injury induces degeneration of the olfactory bulb and development of alternatives for functional olfaction

Lecture
Date:
Wednesday, October 26, 2022
Hour: 11:15 - 12:15
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Dr. Tamar Licht
|
Medical Neurobiology The Hebrew University of Jerusalem

The olfactory bulb is the only recipient of direct olfactory sensory input in the brain and is therefore considered indispensable for odor detection. However, some humans demonstrate normal olfaction despite OB absence. The mechanisms involved in preserving olfaction and the pathogenesis leading to this condition are unknown. We use a mouse model mimicking vascular injury typical of the premature brain. We mapped maturation of blood vessels during development and found selective vulnerability of olfactory bulb vasculature during a specific developmental stage. This injury led to the development of adult, healthy mice with 5% - 35% of the original OB size. Mice could perform innate and learned olfactory tasks, and odor-specific sniff-locked responses were recorded from Piriform cortex. Anatomically, olfactory sensory neurons connect to the rudimentary OB and other ectopic regions and lose typical glomerular convergence. Accordingly, mitral/tufted apical dendrite extends beyond the territory of a single glomerulus. These and additional anatomical findings present alternative nose-to-brain connectivity may underlie preservation of olfaction in humans with degenerated olfactory bulbs.

Mapping internal representations with adaptive sampling, massive online experiments and cross-cultural research

Lecture
Date:
Monday, October 24, 2022
Hour: 11:00 - 12:00
Location:
Nella and Leon Benoziyo Building for Biological Sciences
Dr. Nori Jacoby
|
Max Planck Institute for Empirical Aesthetics, Frankfurt Research Group Leader, “Computational Auditory Perception”

Our brain relies on internal representations to support perception, action, and decision-making. Internal representations are usually rich, multidimensional, and cannot be directly observed. How can these internal representations be characterized? How are they affected by experience? My work develops adaptive behavioral paradigms that integrate human decisions into computer algorithms via human-in-the-loop experiments. I combine these paradigms with a data-intensive expansion of the scale and scope of behavioral research by means of massive online experiments and cross-cultural comparative research. This talk presents “adaptive sampling,” a type of experimental paradigm inspired by Monte Carlo Markov Chain techniques. Each successive stimulus depends on a subject's response to the previous stimulus. This process allows us to sample from the complex and high-dimensional joint distribution associated with internal representations and obtain high-resolution maps of perceptual spaces. After introducing these methods and describing their implementation via large-scale online experiments and field experiments around the world, I demonstrate how they can be applied to fundamental questions in the understanding of the human mind. Specifically, I examine how biology and culture influence internal representations and how semantics influence perception.

Limb development: old equation new solution

Lecture
Date:
Wednesday, October 19, 2022
Hour: 10:00 - 11:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Eli Zelzer
|
Dept of Molecular Genetics, WIS

Valence Based Learning in Primate Amygdala Single-Neurons

Lecture
Date:
Sunday, September 4, 2022
Hour: 09:00 - 10:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Tamar Reitich-Stolero (Advisor: Prof. Rony Paz Lab)
|
Dept of Brain Sciences Student Seminar - PhD Thesis Defense

Humans and animals tend to behave differently when learning from rewarding or aversive feedback, and the amygdala is hypothesized to play a role in these differences. Here, we studied neural mechanisms of learning and decision making in reward and punishment, namely post-stimulus rehearsal, balancing of exploration and exploitation and generalization. To study post-stimulus rehearsal in amygdala neurons, we investigated spike-sequences across simultaneously recorded neurons of non-human primates, while they learned to discriminate between aversive and pleasant tone-odor associations. We showed that valence specific sequences across amygdala neurons rehearsed the coding of the recent association, so they can serve as a coding mechanism that enhances memory formation by rehearsal of the recent association. Next, to examine neural coding of exploration under rewards and punishments, we recorded single neurons while human subjects were engaged in a probabilistic decision-making task with gain and loss conditions, and found more exploration when subjects tried to minimize their losses. We found two mechanisms of explorational choices: one is executed through firing rate of single neurons in the temporal cortex and amygdala and is shared across valence, and the other is executed by an increase in noise in amygdala neurons, and is specific to the loss condition. Finally, we found that over-generalization around a loss-conditioned tone was accompanied by a similar over response of amygdala neurons. Together, this work expands the knowledge of neural mechanisms that enhance learning and improves decision making, specifically in complex environments that include opportunities for rewards and risks for punishments. Zoom link: https://weizmann.zoom.us/j/96622589021?pwd=Tkh1RWk0OFhaVFE0SW9KeU84Q1cvZz09 Meeting ID: 966 2258 9021 Password: 022196

How brains add vectors

Lecture
Date:
Tuesday, August 30, 2022
Hour: 12:30 - 13:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Gaby Maimon
|
Laboratory of Integrative Brain Function The Rockefeller University

Many cognitive computations rely on the nervous system estimating mathematical vectors, but aside from computer models, how brains represent vectors or perform vector operations remains unknown. In this talk, I will describe how the fly brain performs vector arithmetic in the context of spatial navigation. The central features of this vector calculator inside the insect brain may generalize to other nervous systems and other cognitive domains beyond navigation where vector operations are required.

Emergent collective coding properties in hippocampal neuronal population activity

Lecture
Date:
Monday, August 1, 2022
Hour: 13:00 - 14:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Liron Sheintuch
|
Prof. Yaniv Ziv Lab

Populations of hippocampal neurons have been hypothesized to operate collectively to support the stable maintenance of long-term memories. To test this hypothesis, we performed large-scale calcium imaging in the hippocampus of freely behaving mice that repeatedly explored the same environments over weeks. Surprisingly, we discovered that across separate visits to the same familiar environment, hippocampal neurons can collectively switch between multiple distinct spatial representations, without any apparent changes in sensory input or animal’s behavior. The distinct representations were spatially informative and stable over weeks, and switching between them required a complete disconnection of the animal from the environment, demonstrating the coexistence of distinct stable attractors in the hippocampal network. In the second part of the talk, I will present a comparison of the coding properties between hippocampal subfields CA1 and CA3 in novel environments. Place cells in CA3 had more precise and stable spatial tuning than place cells in CA1. Moreover, we showed that in CA3 the tuning of place cells exhibited a higher statistical dependence with their peers compared to in CA1, uncovering an organization of CA3 into cell assemblies. Interestingly, cells with stronger tuning peer-dependence had higher stability but not higher precision, suggesting that distinct mechanisms control these two aspects of the neural code. Overall, our results demonstrate that multiple attractor states can stably coexist in the hippocampus and suggest that a cell-assembly organization in hippocampal CA3 underlies the long-term maintenance of stable spatial codes. Link:https://weizmann.zoom.us/j/97167587409?pwd=TDFFYWI0ZmF5YXk0TW5oN1ZKSStndz09 Meeting ID: 971 6758 7409 Password: 227875

Pages

All events, All years

Deciphering non-neuronal cells contribution to Alzheimer’s disease pathology using high throughput transcriptomic and proteomic methods

Lecture
Date:
Wednesday, November 30, 2022
Hour: 14:00 - 15:00
Location:
Dept of Brain Sciences,Dr. Michal Schwartz,Sedi Medina (PhD Thesis Defense Seminar) on Zoom

Alzheimer's disease (AD) is a devastating pathology of the central nervous system (CNS) of unknown etiology which represents the most common neurodegenerative disorder. For decades, AD was perceived as a disease of the neuron alone. However, research advances in recent years have challenged this concept and shed light on the critical roles of non-neuronal cells on the development and progression of AD. In my PhD, I focused on understanding how two non-neuronal cell types - the Astrocytes and Microglia - respond to AD and how they possibly affect pathological processes. Our research identified a unique population of Astrocytes that significantly increased in association with brain pathology, which we termed disease-associated astrocytes (DAAs). This novel population of DAAs appeared at an early disease stage, increased in abundance with disease progression, and was not observed in young or in healthy adult animals. In addition, similar astrocytes appeared in aged wild-type (WT) mice and in aging human brains, suggesting their linkage to genetic and age-related factors. Aging is considered the greatest risk factor for AD, although the mechanism underlying the aging-related susceptibility to AD is unknown. One emerging factor that is involved in biological aging is the accumulation of senescent cells. Cellular senescence is a process in which aging cells change their characteristic phenotype. Under physiological conditions senescent cells can be removed by the immune system, however with aging, senescent cells accumulate in tissues, either due to a failure of effective removal or due to the accelerated formation of senescent cells. Our data highlight the contribution of non neuronal cells to AD pathogenesis by demonstrating  that 1. Overexpression of a specific gene by astrocytes affected the microglia cells' state, leading to a more homeostatic and less reactive microglial phenotype in comparison to the control group. 2. Accumulation of senescent microglia cells was observed in the brain of aged WT mice and AD mouse model (5xFAD), and by applying different therapeutic strategies we managed to observe significant quantitative differences in these cells, followed by a cognitive amelioration.

Organization of long-term behavior and individuality across developmental timescales

Lecture
Date:
Tuesday, November 29, 2022
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Shay Stern
|
Faculty of Biology TECHNION Haifa

Animals generate complex patterns of behavior across life that can be modified over days, months, or even years. Across these long timescales individuals within the same population may show stereotyped behaviors, but also unique behaviors that distinguish them from each other. How are long-term patterns of behavior organized and regulated across development? And what are the underlying processes that establish and modify individual-to-individual behavioral variation? By utilizing parallel long-term behavioral monitoring at high spatiotemporal resolution of multiple C. elegans individuals across their complete development time we demonstrate temporal regulation of behavioral plasticity by neuromodulators across developmental stages, structuring shared and unique individual responses to early-life experiences. I will further describe our development of unsupervised analyses of individual biases across development based on locomotion trajectory and individual postures which uncovered a large spectrum of individuality types within the isogenic populations. Lastly, I will present preliminary results suggesting that specific neuronal pathways are required to robustly synchronize long-term behavior with development time.

Molecular maps for odor processing in the mouse olfactory system

Lecture
Date:
Tuesday, November 22, 2022
Hour: 12:30 - 13:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Alexander Fleischmann
|
Brown University, Providence, USA

We are interested in the organization and function of neural circuits for sensory processing and behavior. A main goal of the lab is to integrate complementary approaches of system interrogation: we study the molecular diversity of cell types, their connectivity and functional properties; we investigate network dynamics and core computational principles; and we explore how learning and experience shapes behavioral decisions. I will discuss ongoing work aimed at characterizing molecular maps for odor processing in the mouse olfactory bulb. I will present preliminary data using spatial transcriptomics to generate a comprehensive map of glomerular identity and domain structure of the olfactory bulb. Furthermore, I will discuss single cell sequencing experiments and gene regulatory network models that define the diversity and connectivity of olfactory bulb projection neurons. I will try to illustrate how the early olfactory system of mice provides an ideal model system to integrate molecular biology, functional imaging, and behavioral experiments to address fundamental questions in sensory processing and behavior.

Skeletal muscle differentiation and fusion across scales

Lecture
Date:
Wednesday, November 9, 2022
Hour: 10:00 - 11:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Ori Avinoam
|
Dept of Biomolecular Sciences

Selective vascular injury induces degeneration of the olfactory bulb and development of alternatives for functional olfaction

Lecture
Date:
Wednesday, October 26, 2022
Hour: 11:15 - 12:15
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Dr. Tamar Licht
|
Medical Neurobiology The Hebrew University of Jerusalem

The olfactory bulb is the only recipient of direct olfactory sensory input in the brain and is therefore considered indispensable for odor detection. However, some humans demonstrate normal olfaction despite OB absence. The mechanisms involved in preserving olfaction and the pathogenesis leading to this condition are unknown. We use a mouse model mimicking vascular injury typical of the premature brain. We mapped maturation of blood vessels during development and found selective vulnerability of olfactory bulb vasculature during a specific developmental stage. This injury led to the development of adult, healthy mice with 5% - 35% of the original OB size. Mice could perform innate and learned olfactory tasks, and odor-specific sniff-locked responses were recorded from Piriform cortex. Anatomically, olfactory sensory neurons connect to the rudimentary OB and other ectopic regions and lose typical glomerular convergence. Accordingly, mitral/tufted apical dendrite extends beyond the territory of a single glomerulus. These and additional anatomical findings present alternative nose-to-brain connectivity may underlie preservation of olfaction in humans with degenerated olfactory bulbs.

Mapping internal representations with adaptive sampling, massive online experiments and cross-cultural research

Lecture
Date:
Monday, October 24, 2022
Hour: 11:00 - 12:00
Location:
Nella and Leon Benoziyo Building for Biological Sciences
Dr. Nori Jacoby
|
Max Planck Institute for Empirical Aesthetics, Frankfurt Research Group Leader, “Computational Auditory Perception”

Our brain relies on internal representations to support perception, action, and decision-making. Internal representations are usually rich, multidimensional, and cannot be directly observed. How can these internal representations be characterized? How are they affected by experience? My work develops adaptive behavioral paradigms that integrate human decisions into computer algorithms via human-in-the-loop experiments. I combine these paradigms with a data-intensive expansion of the scale and scope of behavioral research by means of massive online experiments and cross-cultural comparative research. This talk presents “adaptive sampling,” a type of experimental paradigm inspired by Monte Carlo Markov Chain techniques. Each successive stimulus depends on a subject's response to the previous stimulus. This process allows us to sample from the complex and high-dimensional joint distribution associated with internal representations and obtain high-resolution maps of perceptual spaces. After introducing these methods and describing their implementation via large-scale online experiments and field experiments around the world, I demonstrate how they can be applied to fundamental questions in the understanding of the human mind. Specifically, I examine how biology and culture influence internal representations and how semantics influence perception.

Limb development: old equation new solution

Lecture
Date:
Wednesday, October 19, 2022
Hour: 10:00 - 11:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Eli Zelzer
|
Dept of Molecular Genetics, WIS

Valence Based Learning in Primate Amygdala Single-Neurons

Lecture
Date:
Sunday, September 4, 2022
Hour: 09:00 - 10:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Tamar Reitich-Stolero (Advisor: Prof. Rony Paz Lab)
|
Dept of Brain Sciences Student Seminar - PhD Thesis Defense

Humans and animals tend to behave differently when learning from rewarding or aversive feedback, and the amygdala is hypothesized to play a role in these differences. Here, we studied neural mechanisms of learning and decision making in reward and punishment, namely post-stimulus rehearsal, balancing of exploration and exploitation and generalization. To study post-stimulus rehearsal in amygdala neurons, we investigated spike-sequences across simultaneously recorded neurons of non-human primates, while they learned to discriminate between aversive and pleasant tone-odor associations. We showed that valence specific sequences across amygdala neurons rehearsed the coding of the recent association, so they can serve as a coding mechanism that enhances memory formation by rehearsal of the recent association. Next, to examine neural coding of exploration under rewards and punishments, we recorded single neurons while human subjects were engaged in a probabilistic decision-making task with gain and loss conditions, and found more exploration when subjects tried to minimize their losses. We found two mechanisms of explorational choices: one is executed through firing rate of single neurons in the temporal cortex and amygdala and is shared across valence, and the other is executed by an increase in noise in amygdala neurons, and is specific to the loss condition. Finally, we found that over-generalization around a loss-conditioned tone was accompanied by a similar over response of amygdala neurons. Together, this work expands the knowledge of neural mechanisms that enhance learning and improves decision making, specifically in complex environments that include opportunities for rewards and risks for punishments. Zoom link: https://weizmann.zoom.us/j/96622589021?pwd=Tkh1RWk0OFhaVFE0SW9KeU84Q1cvZz09 Meeting ID: 966 2258 9021 Password: 022196

How brains add vectors

Lecture
Date:
Tuesday, August 30, 2022
Hour: 12:30 - 13:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Gaby Maimon
|
Laboratory of Integrative Brain Function The Rockefeller University

Many cognitive computations rely on the nervous system estimating mathematical vectors, but aside from computer models, how brains represent vectors or perform vector operations remains unknown. In this talk, I will describe how the fly brain performs vector arithmetic in the context of spatial navigation. The central features of this vector calculator inside the insect brain may generalize to other nervous systems and other cognitive domains beyond navigation where vector operations are required.

Emergent collective coding properties in hippocampal neuronal population activity

Lecture
Date:
Monday, August 1, 2022
Hour: 13:00 - 14:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Liron Sheintuch
|
Prof. Yaniv Ziv Lab

Populations of hippocampal neurons have been hypothesized to operate collectively to support the stable maintenance of long-term memories. To test this hypothesis, we performed large-scale calcium imaging in the hippocampus of freely behaving mice that repeatedly explored the same environments over weeks. Surprisingly, we discovered that across separate visits to the same familiar environment, hippocampal neurons can collectively switch between multiple distinct spatial representations, without any apparent changes in sensory input or animal’s behavior. The distinct representations were spatially informative and stable over weeks, and switching between them required a complete disconnection of the animal from the environment, demonstrating the coexistence of distinct stable attractors in the hippocampal network. In the second part of the talk, I will present a comparison of the coding properties between hippocampal subfields CA1 and CA3 in novel environments. Place cells in CA3 had more precise and stable spatial tuning than place cells in CA1. Moreover, we showed that in CA3 the tuning of place cells exhibited a higher statistical dependence with their peers compared to in CA1, uncovering an organization of CA3 into cell assemblies. Interestingly, cells with stronger tuning peer-dependence had higher stability but not higher precision, suggesting that distinct mechanisms control these two aspects of the neural code. Overall, our results demonstrate that multiple attractor states can stably coexist in the hippocampus and suggest that a cell-assembly organization in hippocampal CA3 underlies the long-term maintenance of stable spatial codes. Link:https://weizmann.zoom.us/j/97167587409?pwd=TDFFYWI0ZmF5YXk0TW5oN1ZKSStndz09 Meeting ID: 971 6758 7409 Password: 227875

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