All events, All years

Architecture and function of small neuronal networks

Lecture
Date:
Monday, June 6, 2022
Hour: 13:30 - 15:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Adam Haber
|
Prof. Elad Schneidman Lab

Neurons in the brain form complex networks of synaptic connections. These elaborate networks define the physical scaffold on which neural activity occurs, and shape the collective dynamics of groups of neurons. In this talk, I will present my work on understanding the structural design principles of neural networks, and the relations between their architecture and their functional properties. First, I will ask what are the structural features that shape the function of neural networks, and show we can learn these features from large ensembles of simulated networks. Second, I will discuss how a strong biological constraint on the structure of neural networks does not incur a computational cost, and may even be functionally beneficial. Third, I will show how we can build connectomes which capture both the structure and the function of real data, using a small number of simple biological features.   Zoom Link: https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421

Fast multimodal imaging of brain dynamics underlying sleep and wakefulness

Lecture
Date:
Tuesday, May 17, 2022
Hour: 14:00 - 15:00
Location:
Dr. Laura Lewis
|
Center for Systems Neuroscience Boston University

When we fall asleep, brain function and physiology are rapidly transformed. Understanding the neural basis of sleep requires imaging methods that can capture multiple aspects of brain physiology at fast timescales. We develop approaches for analyzing human brain physiology using multimodal neuroimaging, and apply them to investigate the neural origins and consequences of sleep. We found that accelerated methods for fMRI can enable imaging subsecond neural dynamics throughout the human brain. We applied these methods to investigate the neural dynamics that occur at state transitions, and identified temporal sequences within thalamocortical networks that precede the moment of awakening from sleep. In addition, we developed a method to image cerebrospinal fluid flow, and discovered large waves of fluid flow that appear in the sleeping human brain. Together, these studies highlight the new biological information that can be extracted from fast fMRI data, and use this approach to discover neurophysiological dynamics unique to the sleeping brain. Link: https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421

Brain plasticity: Regulation and Modulation

Conference
Date:
Monday, May 16, 2022
Hour: 08:00 - 18:00
Location:
The David Lopatie Conference Centre

Models of Human Memory

Lecture
Date:
Tuesday, May 3, 2022
Hour: 12:30 - 13:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Misha Tsodyks
|
Dept of Brain Sciences, WIS

Human memory is a multi-stage process that in real life cannot be easily quantified let alone predicted by any kind of mathematical model. Cognitive psychologists developed experimental paradigms to overcome the first problem by using randomly assembled lists of words or other items for recognition and recall. Results of these experiments can be precisely characterized, and we recently proposed a set of mathematical models that are based on simple assumptions that can be analytically solved and provide surprisingly accurate predictions tested on Amazon Mechanical Turk internet platform. The main innovation of this approach to modeling memory is that (i) it is based on a very small set of basic principles and has little to no free parameters and (ii) assumes deterministic processes underlying memory. In particular, our recall model results in the prediction with not a single free parameter, indicating full universality of this memory component. Our model for forgetting has one free integer parameter, and indeed our experiments show that different types of items exhibit different rate of forgetting. The most ambitious part of this project is to generalize the quantitative approach to memory to more meaningful material such as narratives. We are designing quantitative measures of performance in these experiments. Our preliminary results indicate interesting features of performance for meaningful material, in particular the recall is more structured and uniform across subjects. We believe that better understanding of memory processes with meaningful material will allow the future AI systems to achieve a better and more ‘human’ level of processing of natural language.

Representation of 3D space in the mammalian brain: From 3D grid cells in flying bats to 3D perception in flying humans

Lecture
Date:
Wednesday, April 27, 2022
Hour: 12:30 - 13:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Gily Ginosar
|
Prof. Nachum Ulanovsky Lab Dept of Brain Sciences, WIS

While our world is three-dimensional (3D), spatial perception is most often studied in animals and humans navigating across 2D surfaces. I will present two cases in which the consideration of the 3D nature of the world has led us to surprising results. The first case regards the neural recording of mammalian grid cells. Grid cells that are recorded over 2D surfaces create a hexagonal-shaped repetitive lattice, which inspired many theoretical studies to investigate the pattern’s mechanism and function. Upon recording in bats flying through 3D space, we found that grid cells did not exhibit a hexagonal global lattice, but rather showed a local order – with grid-fields exhibiting fixed local distances. Our results in 3D strongly argue against most of the prevailing models of grid-cell function, and we suggest a unified model that explains the results in both 2D and 3D.  The second case regards the perception of 3D space in humans. Different behavioral studies have shown contradicting evidence of human perception of 3D space being either isotropic or vertically compressed. We addressed this question using human experts in 3D motion and navigation – fighter pilots – studied in a flight simulator. We considered two aspects of the perception of 3D space: surrounding space and travelled space. We show that different aspects of the perception of space are shaped differently with experience: whereas the perception of the 3D surrounding space was vertically compressed in both expert and non-expert subjects, fighter pilots exhibited isotropic perception of travelled space, whereas non-expert subjects retained a distorted perception.  Together, our research sheds light on the differences and similarities between the coding of 3D versus 2D space, in both animals and humans.  

Dopamine release is inversely related to economic demand

Lecture
Date:
Tuesday, April 26, 2022
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Neir Eshel
|
Dept of Psychiatry and Behavioral Sciences Stanford University

Decision-making requires a consideration of both costs and benefits. Although mesolimbic dopamine (DA) plays an established role in reward-related decisions, there has been longstanding controversy over its sensitivity to costs vs benefits. Manipulations of DA function imply a primary role in mediating cost calculations, while DA recordings suggest a preference for encoding benefit. These studies often confound cost and benefit by varying both simultaneously, and rarely combine correlational and causal tools to explore how encoding relates to behavior. Here we independently varied costs and benefits, studying DA's role using both recording and manipulation. We found that DA release reflects changes in both cost and benefit, although the precise relationship depended on the time within a trial and the site of DA release. Then we used behavioral economics to probe how these patterns of DA release relate to two important behavioral parameters: a mouse's preferred level of reward consumption and the amount of work it is willing to expend to maintain that consumption. We found that DA release in the nucleus accumbens core and dorsolateral striatum does not predict an animal's preferred level of consumption. It does, however, strongly reflect an animal's willingness to work for reward. Surprisingly, the more DA released for each reward, the less demand for that reward. The inverse relationship between DA release and demand held true both for natural rewards and optogenetic stimulation of DA release in both striatal targets. Our findings support an inverted-U model of dopamine and reinforcement, where a minimal level of DA release is critical to motivate behavior, but increments above that level actually reduce demand. Link to join: https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421

An attempt to account for multiple perceptual memory behaviors in a single framework

Lecture
Date:
Wednesday, April 13, 2022
Hour: 15:00 - 16:00
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Mathew Diamond
|
Cognitive Neuroscience SISSA Trieste Italy

Rats (if trained appropriately) can apply to some set of tactile stimuli a multitude of different perceptual and memory capacities. For instance, they can express working memory, where the most recent stimulus has to be stored and retrieved to support a comparison to the ongoing stimulus. They can express reference memory, where the ongoing stimulus has to be compared to some stable, internal boundary. They can change that internal boundary as a function of stimulus statistics. They can learn to ignore stimuli of the same sensory modality, if untagged by an acoustic cue. While it might seem easiest to draw up computational/functional frameworks tailor-made to each behavior, we are trying to explain several different behaviors by common algorithms. This informal discussion will mainly present ongoing psychophysical studies, with a few preliminary physiological added here and there.  

Fragmenting the self: brainwide recording and the neurobiology of dissociation

Lecture
Date:
Wednesday, April 13, 2022
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Dr. Isaac Kauvar
|
Postdoc, Neuroscience Institute, Stanford University

Advanced methods now allow fast, cellular-level recording of neural activity across the mammalian brain, enabling exploration of how brain-wide dynamical patterns might give rise to complex behavioral states, such as the clinically important state of dissociation. We established a dissociation-like state in mice, induced by administration of ketamine or phencyclidine. Large-scale neural recording revealed that these dissociative agents elicited a 1–3-Hz rhythm in layer 5 neurons of retrosplenial cortex, uncoupled from most other brain regions except thalamus. Additionally, using brain-wide intracranial electrical recording in a patient with focal epilepsy, the human experience of dissociation was linked to a similar ~3 Hz rhythm in posteromedial cortex (homologous to mouse retrosplenial cortex), and stimulation of this area induced dissociation.   

Daily normalization of E/I-ratio by light-driven transcription maintains visual processing by Dahlia Kushinsky, PhD Student, Advisor: Dr. Ivo Spiegel and Isolated correlates of perception in the posterior cortex by Michael Sokoletsky, PhD Student, Advisor

Lecture
Date:
Tuesday, April 12, 2022
Hour: 12:30 - 13:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Dahlia Kushinsky, PhD Student, Advisor: Dr. Ivo Spiegel and Michael Sokoletsky, PhD Student, Advisor: Prof. Ilan Lampl
|
Students Seminar Department of Brain Sciences

Dahlia Kushinsky- Daily normalization of E/I-ratio by light-driven transcription maintains visual processing Abstract: Consistent and reliable encoding of sensory information is essential for an animal’s survival. However, sensory input in an animal’s environment is constantly changing, likely resulting in changes in the brain at the level of molecules, synapses, and cellular circuitry. It is therefore unclear which elements of the system are stable or dynamic, and what mechanisms allow for overall stability of the brain throughout an animal’s life. To address this question, we focused on the visual cortex of adult mice and took advantage of the daily sensory transitions from the dark of night to daylight and back to darkness during a single day. By using RNA-seq, patch clamp slice electrophysiology, and in vivo longitudinal calcium imaging in awake mice, we monitor the light driven changes in molecules, synapses, and cells across a single day. At each of these levels (molecular, synaptic, and cellular), we find rapid sensory-driven increases shortly after transition from darkness to light which is then normalized later in the day. Based on these findings, we suggest that sensory-driven genetic changes maintain functional stability of neural circuits by regulating E/I ratio in excitatory neurons every day. Michael Sokoletsy- Isolated correlates of perception in the posterior cortex Abstract: To uncover the neural mechanisms of stimulus perception, experimenters commonly use tasks in which subjects are repeatedly presented with a weak stimulus and instructed to report, via movement, if they perceived the stimulus. The difference in neural activity between reported stimulus (hit) and unreported stimulus (miss) trials is then seen as potentially perception-related. However, recent studies found that activity related to the report spreads throughout the brain, calling into question to what extent such tasks may be conflating activity that is perception-related with activity that is report-related. To isolate perception-related activity, we developed a paradigm in which the same mice were trained to report either the presence or absence of a whisker stimulus. We found that isolated perception-related activity appeared within a posterio-parietal network of cortical regions contralateral to the stimulus, was on average an order of magnitude lower than the hit versus miss difference, and began just after the low-level stimulus response. In addition, we performed controls to check that it is specifically associated with performance and is not the result of differences in time or uninstructed movements across the tasks. In summary, we revealed for the first time in mice the cortical areas that are associated specifically with the perception of a sensory stimulus and independently of the report.

Conscious intentions during voluntary action formation

Lecture
Date:
Tuesday, April 5, 2022
Hour: 12:30 - 13:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Dr. Uri Maoz
|
Computational Neuroscience Chapman University Visiting Assistant Professor-UCLA Visiting Associate-Caltech

Investigating conscious intentions associated with spontaneous, voluntary action is challenging. Typical paradigms inherently lack the stimulus-response structure that is common in neuroscientific tasks (Haggard, 2019). Moreover, studying the onset of intentions has proven notoriously difficult, conceptually and empirically. Measuring the onset of intentions with a clock was shown to be inconsistent, biased, and unreliable (Maoz et al., 2015). Furthermore, probe methods estimated intention onset much earlier than clock-based methods (Matsuhashi & Hallett, 2008), complicating the reconciliation of these results. Some have even questioned the existence of intentions as discrete, causal neural states (Schurger & Utihol, 2015).

Pages

All events, All years

Architecture and function of small neuronal networks

Lecture
Date:
Monday, June 6, 2022
Hour: 13:30 - 15:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Adam Haber
|
Prof. Elad Schneidman Lab

Neurons in the brain form complex networks of synaptic connections. These elaborate networks define the physical scaffold on which neural activity occurs, and shape the collective dynamics of groups of neurons. In this talk, I will present my work on understanding the structural design principles of neural networks, and the relations between their architecture and their functional properties. First, I will ask what are the structural features that shape the function of neural networks, and show we can learn these features from large ensembles of simulated networks. Second, I will discuss how a strong biological constraint on the structure of neural networks does not incur a computational cost, and may even be functionally beneficial. Third, I will show how we can build connectomes which capture both the structure and the function of real data, using a small number of simple biological features.   Zoom Link: https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421

Fast multimodal imaging of brain dynamics underlying sleep and wakefulness

Lecture
Date:
Tuesday, May 17, 2022
Hour: 14:00 - 15:00
Location:
Dr. Laura Lewis
|
Center for Systems Neuroscience Boston University

When we fall asleep, brain function and physiology are rapidly transformed. Understanding the neural basis of sleep requires imaging methods that can capture multiple aspects of brain physiology at fast timescales. We develop approaches for analyzing human brain physiology using multimodal neuroimaging, and apply them to investigate the neural origins and consequences of sleep. We found that accelerated methods for fMRI can enable imaging subsecond neural dynamics throughout the human brain. We applied these methods to investigate the neural dynamics that occur at state transitions, and identified temporal sequences within thalamocortical networks that precede the moment of awakening from sleep. In addition, we developed a method to image cerebrospinal fluid flow, and discovered large waves of fluid flow that appear in the sleeping human brain. Together, these studies highlight the new biological information that can be extracted from fast fMRI data, and use this approach to discover neurophysiological dynamics unique to the sleeping brain. Link: https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421

Models of Human Memory

Lecture
Date:
Tuesday, May 3, 2022
Hour: 12:30 - 13:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Misha Tsodyks
|
Dept of Brain Sciences, WIS

Human memory is a multi-stage process that in real life cannot be easily quantified let alone predicted by any kind of mathematical model. Cognitive psychologists developed experimental paradigms to overcome the first problem by using randomly assembled lists of words or other items for recognition and recall. Results of these experiments can be precisely characterized, and we recently proposed a set of mathematical models that are based on simple assumptions that can be analytically solved and provide surprisingly accurate predictions tested on Amazon Mechanical Turk internet platform. The main innovation of this approach to modeling memory is that (i) it is based on a very small set of basic principles and has little to no free parameters and (ii) assumes deterministic processes underlying memory. In particular, our recall model results in the prediction with not a single free parameter, indicating full universality of this memory component. Our model for forgetting has one free integer parameter, and indeed our experiments show that different types of items exhibit different rate of forgetting. The most ambitious part of this project is to generalize the quantitative approach to memory to more meaningful material such as narratives. We are designing quantitative measures of performance in these experiments. Our preliminary results indicate interesting features of performance for meaningful material, in particular the recall is more structured and uniform across subjects. We believe that better understanding of memory processes with meaningful material will allow the future AI systems to achieve a better and more ‘human’ level of processing of natural language.

Representation of 3D space in the mammalian brain: From 3D grid cells in flying bats to 3D perception in flying humans

Lecture
Date:
Wednesday, April 27, 2022
Hour: 12:30 - 13:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Gily Ginosar
|
Prof. Nachum Ulanovsky Lab Dept of Brain Sciences, WIS

While our world is three-dimensional (3D), spatial perception is most often studied in animals and humans navigating across 2D surfaces. I will present two cases in which the consideration of the 3D nature of the world has led us to surprising results. The first case regards the neural recording of mammalian grid cells. Grid cells that are recorded over 2D surfaces create a hexagonal-shaped repetitive lattice, which inspired many theoretical studies to investigate the pattern’s mechanism and function. Upon recording in bats flying through 3D space, we found that grid cells did not exhibit a hexagonal global lattice, but rather showed a local order – with grid-fields exhibiting fixed local distances. Our results in 3D strongly argue against most of the prevailing models of grid-cell function, and we suggest a unified model that explains the results in both 2D and 3D.  The second case regards the perception of 3D space in humans. Different behavioral studies have shown contradicting evidence of human perception of 3D space being either isotropic or vertically compressed. We addressed this question using human experts in 3D motion and navigation – fighter pilots – studied in a flight simulator. We considered two aspects of the perception of 3D space: surrounding space and travelled space. We show that different aspects of the perception of space are shaped differently with experience: whereas the perception of the 3D surrounding space was vertically compressed in both expert and non-expert subjects, fighter pilots exhibited isotropic perception of travelled space, whereas non-expert subjects retained a distorted perception.  Together, our research sheds light on the differences and similarities between the coding of 3D versus 2D space, in both animals and humans.  

Dopamine release is inversely related to economic demand

Lecture
Date:
Tuesday, April 26, 2022
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Neir Eshel
|
Dept of Psychiatry and Behavioral Sciences Stanford University

Decision-making requires a consideration of both costs and benefits. Although mesolimbic dopamine (DA) plays an established role in reward-related decisions, there has been longstanding controversy over its sensitivity to costs vs benefits. Manipulations of DA function imply a primary role in mediating cost calculations, while DA recordings suggest a preference for encoding benefit. These studies often confound cost and benefit by varying both simultaneously, and rarely combine correlational and causal tools to explore how encoding relates to behavior. Here we independently varied costs and benefits, studying DA's role using both recording and manipulation. We found that DA release reflects changes in both cost and benefit, although the precise relationship depended on the time within a trial and the site of DA release. Then we used behavioral economics to probe how these patterns of DA release relate to two important behavioral parameters: a mouse's preferred level of reward consumption and the amount of work it is willing to expend to maintain that consumption. We found that DA release in the nucleus accumbens core and dorsolateral striatum does not predict an animal's preferred level of consumption. It does, however, strongly reflect an animal's willingness to work for reward. Surprisingly, the more DA released for each reward, the less demand for that reward. The inverse relationship between DA release and demand held true both for natural rewards and optogenetic stimulation of DA release in both striatal targets. Our findings support an inverted-U model of dopamine and reinforcement, where a minimal level of DA release is critical to motivate behavior, but increments above that level actually reduce demand. Link to join: https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421

An attempt to account for multiple perceptual memory behaviors in a single framework

Lecture
Date:
Wednesday, April 13, 2022
Hour: 15:00 - 16:00
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Mathew Diamond
|
Cognitive Neuroscience SISSA Trieste Italy

Rats (if trained appropriately) can apply to some set of tactile stimuli a multitude of different perceptual and memory capacities. For instance, they can express working memory, where the most recent stimulus has to be stored and retrieved to support a comparison to the ongoing stimulus. They can express reference memory, where the ongoing stimulus has to be compared to some stable, internal boundary. They can change that internal boundary as a function of stimulus statistics. They can learn to ignore stimuli of the same sensory modality, if untagged by an acoustic cue. While it might seem easiest to draw up computational/functional frameworks tailor-made to each behavior, we are trying to explain several different behaviors by common algorithms. This informal discussion will mainly present ongoing psychophysical studies, with a few preliminary physiological added here and there.  

Fragmenting the self: brainwide recording and the neurobiology of dissociation

Lecture
Date:
Wednesday, April 13, 2022
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Dr. Isaac Kauvar
|
Postdoc, Neuroscience Institute, Stanford University

Advanced methods now allow fast, cellular-level recording of neural activity across the mammalian brain, enabling exploration of how brain-wide dynamical patterns might give rise to complex behavioral states, such as the clinically important state of dissociation. We established a dissociation-like state in mice, induced by administration of ketamine or phencyclidine. Large-scale neural recording revealed that these dissociative agents elicited a 1–3-Hz rhythm in layer 5 neurons of retrosplenial cortex, uncoupled from most other brain regions except thalamus. Additionally, using brain-wide intracranial electrical recording in a patient with focal epilepsy, the human experience of dissociation was linked to a similar ~3 Hz rhythm in posteromedial cortex (homologous to mouse retrosplenial cortex), and stimulation of this area induced dissociation.   

Daily normalization of E/I-ratio by light-driven transcription maintains visual processing by Dahlia Kushinsky, PhD Student, Advisor: Dr. Ivo Spiegel and Isolated correlates of perception in the posterior cortex by Michael Sokoletsky, PhD Student, Advisor

Lecture
Date:
Tuesday, April 12, 2022
Hour: 12:30 - 13:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Dahlia Kushinsky, PhD Student, Advisor: Dr. Ivo Spiegel and Michael Sokoletsky, PhD Student, Advisor: Prof. Ilan Lampl
|
Students Seminar Department of Brain Sciences

Dahlia Kushinsky- Daily normalization of E/I-ratio by light-driven transcription maintains visual processing Abstract: Consistent and reliable encoding of sensory information is essential for an animal’s survival. However, sensory input in an animal’s environment is constantly changing, likely resulting in changes in the brain at the level of molecules, synapses, and cellular circuitry. It is therefore unclear which elements of the system are stable or dynamic, and what mechanisms allow for overall stability of the brain throughout an animal’s life. To address this question, we focused on the visual cortex of adult mice and took advantage of the daily sensory transitions from the dark of night to daylight and back to darkness during a single day. By using RNA-seq, patch clamp slice electrophysiology, and in vivo longitudinal calcium imaging in awake mice, we monitor the light driven changes in molecules, synapses, and cells across a single day. At each of these levels (molecular, synaptic, and cellular), we find rapid sensory-driven increases shortly after transition from darkness to light which is then normalized later in the day. Based on these findings, we suggest that sensory-driven genetic changes maintain functional stability of neural circuits by regulating E/I ratio in excitatory neurons every day. Michael Sokoletsy- Isolated correlates of perception in the posterior cortex Abstract: To uncover the neural mechanisms of stimulus perception, experimenters commonly use tasks in which subjects are repeatedly presented with a weak stimulus and instructed to report, via movement, if they perceived the stimulus. The difference in neural activity between reported stimulus (hit) and unreported stimulus (miss) trials is then seen as potentially perception-related. However, recent studies found that activity related to the report spreads throughout the brain, calling into question to what extent such tasks may be conflating activity that is perception-related with activity that is report-related. To isolate perception-related activity, we developed a paradigm in which the same mice were trained to report either the presence or absence of a whisker stimulus. We found that isolated perception-related activity appeared within a posterio-parietal network of cortical regions contralateral to the stimulus, was on average an order of magnitude lower than the hit versus miss difference, and began just after the low-level stimulus response. In addition, we performed controls to check that it is specifically associated with performance and is not the result of differences in time or uninstructed movements across the tasks. In summary, we revealed for the first time in mice the cortical areas that are associated specifically with the perception of a sensory stimulus and independently of the report.

Conscious intentions during voluntary action formation

Lecture
Date:
Tuesday, April 5, 2022
Hour: 12:30 - 13:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Dr. Uri Maoz
|
Computational Neuroscience Chapman University Visiting Assistant Professor-UCLA Visiting Associate-Caltech

Investigating conscious intentions associated with spontaneous, voluntary action is challenging. Typical paradigms inherently lack the stimulus-response structure that is common in neuroscientific tasks (Haggard, 2019). Moreover, studying the onset of intentions has proven notoriously difficult, conceptually and empirically. Measuring the onset of intentions with a clock was shown to be inconsistent, biased, and unreliable (Maoz et al., 2015). Furthermore, probe methods estimated intention onset much earlier than clock-based methods (Matsuhashi & Hallett, 2008), complicating the reconciliation of these results. Some have even questioned the existence of intentions as discrete, causal neural states (Schurger & Utihol, 2015).

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

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