All events, 2018

Ca2+ stores in animal models of Alzheimer’s disease

Lecture
Date:
Thursday, December 27, 2018
Hour: 13:30 - 14:45
Location:
Nella and Leon Benoziyo Building for Brain Research
Etay Aloni (PhD Thesis Defense)
|
Menahem Segal Lab, Dept of Neurobiology, WIS

: Intracellular Ca2+ concentration ([Ca2+]i) is tightly regulated in neurons. Ca2+ plays important roles in signal transduction pathways, synaptic plasticity, energy metabolism and apoptosis. In dendritic spines, [Ca2+]i is controlled by voltage and ligand-gated channels that allow Ca2+ entry from the extracellular space and by ryanodine receptors (RyR) and inositol 1,4,5-trisphosphate receptors (IP3R) that release Ca2+ from intracellular stores. Disruption in Ca2+ homeostasis is linked to several pathologies and is suggested to play a pivotal role in the cascade of events leading to Alzheimer disease (AD). In line with this, I found that low concentrations of caffeine, known to release Ca2+ from stores, is more effective in facilitating long-term potentiation (LTP) induction in hippocampal slices of a triple-transgenic (3xTg) mouse model of AD than controls. Synaptopodin (SP) is a protein residing in the dendritic spines. SP is an essential component in the formation of the spine apparatus (SA), which is a specialized form of smooth endoplasmic reticulum (ER) found in dendritic spines. Spines lacking SP were shown to release less Ca2+ from stores. The present study is aimed to explore the involvement of Ca2+ stores in 3xTg mouse model of AD. By crossing 3xTg and SPKO mice lines, I studied the effect of SP deficiency on AD markers in the 3xTg mouse. I found that the 3xTg/SPKO mice show normal learning in a spatial memory task by comparison to the deficiency found in the 3xTg mouse, and express normal LTP in hippocampal slices, which is deficient in 3xTg mice. Furthermore, low concentration of ryanodine has a facilitating effect on LTP induction only in the 3xTg mice group. In addition, these brains do not express amyloid plaques, activated microglia, p-tau overexpression and high RyR expression seen in age matched 3xTg mice, These results suggest that SP deficiency restores [Ca2+]i homeostasis in the 3xTg so as to suppress the progression of AD symptoms.

ORGaNICs: A Canonical Neural Circuit Computation

Lecture
Date:
Sunday, December 23, 2018
Hour: 14:30
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. David Heeger
|
Center for Neural Science and Dept of Psychology, NYU

A theory of cortical function is proposed, based on a family of recurrent neural circuits, called ORGaNICs (Oscillatory Recurrent GAted Neural Integrator Circuits). The theory is applied to working memory and motor control. Working memory is a cognitive process for temporarily maintaining and manipulating information. Most empirical neuroscience research on working memory has measured sustained activity during delayed-response tasks, and most models of working memory are designed to explain sustained activity. But this focus on sustained activity (i.e., maintenance) ignores manipulation, and there are a variety of experimental results that are difficult to reconcile with sustained activity. ORGaNICs can be used to explain the complex dynamics of activity, and ORGaNICs can be use to manipulate (as well as maintain) information during a working memory task. The theory provides a means for reading out information from the dynamically varying responses at any point in time, in spite of the complex dynamics. When applied to motor systems, ORGaNICs can be used to convert spatial patterns of premotor activity to temporal profiles of motor activity: different spatial patterns of premotor activity evoke different temporal response dynamics. ORGaNICs offer a novel conceptual framework; Rethinking cortical computation in these terms should have widespread implications, motivating a variety of experiments.

Functional stability in a dynamic network – the role of inhibition

Lecture
Date:
Tuesday, December 18, 2018
Hour: 12:30
Location:
Nella and Leon Benoziyo Building for Brain Research
Prof. Yonatan Loewenstein
|
Department of Neurobiology – ELSC Hebrew University of Jerusalem

According to the synaptic trace theory of memory, activity-induced changes in the pattern of synaptic connections underlie the storage of information for long periods. In this framework, the stability of memory critically depends on the stability of the underlying synaptic connections. Surprisingly however, the excitatory synaptic connections, which constitute most of the synapses in the cortex, are highly volatile in the living brain, which poses a fundamental challenge to the synaptic trace theory. We show that in the balanced cortex, patterns of neural activity are primarily determined by the inhibitory connectivity, despite the fact that most synapses and neurons are excitatory. Similarly, we show that the inhibitory network is more effective in storing memory patterns than the excitatory one. As a result, network activity is robust to ongoing volatility of excitatory synapses, as long as this volatility does not disrupt the balance between excitation and inhibition. We thus hypothesize that inhibitory connectivity, rather than excitatory, controls the maintenance and loss of information over long periods of time in the volatile cortex.

Learning and sleep-dependent dendritic spine plasticity and maintenance

Lecture
Date:
Thursday, December 6, 2018
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Wenbiao Gan
|
Skirball Institute of Biomolecular Medicine, Molecular Neurobiology, Dept of Neuroscience and Physiology, New York University

Learning and sleep-dependent dendritic spine plasticity and maintenance

Lecture
Date:
Thursday, December 6, 2018
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Wenbiao Gan
|
Skirball Institute of Biomolecular Medicine, Molecular Neurobiology, Dept of Neuroscience and Physiology, New York University

Cellular function given parametric variation in the Hodgkin-Huxley model

Lecture
Date:
Tuesday, November 27, 2018
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Shimon Marom
|
Rappaport Faculty of Medicine, Technion, Haifa

How is reliable physiological function maintained in cells despite considerable variability in the values of key parameters of multiple interacting processes that govern that function? I will describe a possible approach to the problem, through analysis of the classic Hodgkin-Huxley formulation of membrane action potential. Although the full Hodgkin-Huxley model is very sensitive to fluctuations that independently occur in its many parameters, the outcome is in fact determined by simple combinations of these parameters along two physiological dimensions: Structural and Kinetic (denoted S and K). The impacts of parametric fluctuations on the dynamics of the system — seemingly complex in the high dimensional representation of the Hodgkin-Huxley model — are tractable when examined within the S-K plane. Experimental validation of the resulting phase diagram is offered, using a bio-synthetic system.

The Inspirational Brain: Human Non-Olfactory Cognition is Phase-Locked with Sniffing

Lecture
Date:
Thursday, November 22, 2018
Hour: 14:00 - 15:00
Location:
Gerhard M.J. Schmidt Lecture Hall
Ofer Perl (PhD Thesis Defense)
|
Noam Sobel Lab, Dept of Neurobiology, WIS

Olfactory stimulus acquisition is perfectly synchronized with inhalation, which tunes neuronal ensembles for incoming information. Because olfaction is an ancient sensory system that provided a template for brain evolution, we hypothesized that this link persisted, and therefore sniffs may tune the brain for acquisition of non-olfactory information as well. To test this, we measured nasal airflow and electroencephalography during various non-olfactory cognitive tasks. We observed that participants spontaneously inhale at non-olfactory cognitive task onset, and that such inhalations shift brain functional network architecture. Concentrating on visuospatial perception, we observed that inhalation drove increased task-related brain activity in specific task-related brain regions, and resulted in improved performance accuracy in the visuospatial task. Thus, mental processes with no link to olfaction are nevertheless phase-locked with sniffing, consistent with the notion of an olfaction-based template in the evolution of human brain function.

Development of Memory Systems in the Human Brain

Lecture
Date:
Tuesday, November 20, 2018
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Noa Ofen
|
Department of Psychology Institute of Gerontology and Merrill Palmer Institute for Child Development Wayne State University, Detroit

Episodic memory – the ability to encode, maintain and retrieve information – is critical for everyday functioning at all ages, yet little is known about the development of episodic memory systems and their brain substrates. In this talk, I will present data from a series of studies with which we begin to identify how brain development underlies changes in episodic memory throughout childhood and adolescence. Using structural MRI data, I will present evidence demonstrating how brain development sets limits on cognitive developmnet. I will show that individual differences in fine structural measures of the hippocampus, a region known to be critical for episodic memory, and the prefrontal cortex (PFC), a region that shows protracted structural development, partially explain age-related improvement in episodic memory. Using functional neuroimaging methods including functional MRI (fMRI) and electrocorticography (ECoG), I will present our ongoing attempts to characterize the neural correlates of episodic memory development. Evidence from fMRI studies suggest that age differences in episodic memory functioning may primarily relate to age differneces in PFC activation and connectivity patterns. Intracranial evidence further underscores the role of the PFC in memory and reveals that spatiotemporal propagation of frontal activity supports memory formation in children. I will highlight the challenges in investigaitons of brain-behavior relations in pediatric populations and discuss how advances in methodologies provide unique opportunities for moving towards a mechanistic understanding of developmental changes.

Neurophysiology of States of Consciousness: From Mechanistic Principles to Novel Diagnostic and Therapeutic Tools

Lecture
Date:
Thursday, November 15, 2018
Hour: 12:30
Location:
Nella and Leon Benoziyo Building for Brain Research
Prof. Jacobo Diego Sitt
|
MD, PhD, HDR INSERM CRN Sorbonne Universities, UPMC Univ Paris 06 ICM Research Center Pitié Salpêtrière Hospital Paris

Uncovering the neural mechanisms that allow conscious access to information is a major challenge of neuroscience. An incomplete list of still open questions include, What are the necessary brain computational properties to permit access to a stream of conscious contents? What is the relationship between conscious perception, self-awareness and multisensory processing of bodily signals? How these processes change when the brain transitions to an ‘unconscious’ state (like sleep, anaesthesia or pathological conditions)? Can we externally trigger state-of-consciousness (SOC) transitions by means of stimulation? In this presentation I will present my work focus in these relevant scientific and clinical questions. I will present our latest developments including different pre-clinical and clinical experimental models (brain-injuries and/or anesthesia), neuroimaging methods (EEG, fMRI or brain/body interactions) and stimulation techniques (tES, auditory/somatosensory/visual stimulation). Overall I will try to demonstrate that the integration of multimodal neural information provides critical information to characterise the state-of-consciousness in physiological and pathological conditions and might help to predict novel optimal therapeutic strategies.

Perception and retinal integration of rod and cone signals in primate

Lecture
Date:
Tuesday, November 13, 2018
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Dr. William Grimes
|
NINDS/NIH

Over the course of a natural day-night cycle, mean luminance levels can span ten log units or more. Mammalian retinas effectively encode visual information over this vast range, in part by utilizing exquisitely sensitive rod photoreceptors in dim conditions and multiple color-variant cone photoreceptors in bright conditions. These visual signals, regardless of origin, must pass through a common set of retinal ganglion cells, thereby creating opportunities for signal interactions. Human perceptual experiments conducted under intermediate lighting conditions reveal constructive and destructive interactions between flickering rod and cone stimuli that are thought to originate in the retina. In support of this hypothesis, we find rod-cone flicker interference in On and Off retinal ganglion cells that project! to magnocellular visual pathways in primates. The dependence of this interference on the frequency and phase of the temporal modulation is similar to that observed in perceptual measurements. Recordings from within the retinal circuitry indicate that rod-cone signal interference reflects a linear combination of kinetically-distinct rod and cone signals upstream of the ganglion cell synaptic inputs. Ultimately, using our empirically-derived data as a foundation, we construct a mathematical model that recapitulates known rod-cone interactions and predicts retinal output in response to a broad range of time-varying rod and cone stimuli.

Pages

All events, 2018

Ca2+ stores in animal models of Alzheimer’s disease

Lecture
Date:
Thursday, December 27, 2018
Hour: 13:30 - 14:45
Location:
Nella and Leon Benoziyo Building for Brain Research
Etay Aloni (PhD Thesis Defense)
|
Menahem Segal Lab, Dept of Neurobiology, WIS

: Intracellular Ca2+ concentration ([Ca2+]i) is tightly regulated in neurons. Ca2+ plays important roles in signal transduction pathways, synaptic plasticity, energy metabolism and apoptosis. In dendritic spines, [Ca2+]i is controlled by voltage and ligand-gated channels that allow Ca2+ entry from the extracellular space and by ryanodine receptors (RyR) and inositol 1,4,5-trisphosphate receptors (IP3R) that release Ca2+ from intracellular stores. Disruption in Ca2+ homeostasis is linked to several pathologies and is suggested to play a pivotal role in the cascade of events leading to Alzheimer disease (AD). In line with this, I found that low concentrations of caffeine, known to release Ca2+ from stores, is more effective in facilitating long-term potentiation (LTP) induction in hippocampal slices of a triple-transgenic (3xTg) mouse model of AD than controls. Synaptopodin (SP) is a protein residing in the dendritic spines. SP is an essential component in the formation of the spine apparatus (SA), which is a specialized form of smooth endoplasmic reticulum (ER) found in dendritic spines. Spines lacking SP were shown to release less Ca2+ from stores. The present study is aimed to explore the involvement of Ca2+ stores in 3xTg mouse model of AD. By crossing 3xTg and SPKO mice lines, I studied the effect of SP deficiency on AD markers in the 3xTg mouse. I found that the 3xTg/SPKO mice show normal learning in a spatial memory task by comparison to the deficiency found in the 3xTg mouse, and express normal LTP in hippocampal slices, which is deficient in 3xTg mice. Furthermore, low concentration of ryanodine has a facilitating effect on LTP induction only in the 3xTg mice group. In addition, these brains do not express amyloid plaques, activated microglia, p-tau overexpression and high RyR expression seen in age matched 3xTg mice, These results suggest that SP deficiency restores [Ca2+]i homeostasis in the 3xTg so as to suppress the progression of AD symptoms.

ORGaNICs: A Canonical Neural Circuit Computation

Lecture
Date:
Sunday, December 23, 2018
Hour: 14:30
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. David Heeger
|
Center for Neural Science and Dept of Psychology, NYU

A theory of cortical function is proposed, based on a family of recurrent neural circuits, called ORGaNICs (Oscillatory Recurrent GAted Neural Integrator Circuits). The theory is applied to working memory and motor control. Working memory is a cognitive process for temporarily maintaining and manipulating information. Most empirical neuroscience research on working memory has measured sustained activity during delayed-response tasks, and most models of working memory are designed to explain sustained activity. But this focus on sustained activity (i.e., maintenance) ignores manipulation, and there are a variety of experimental results that are difficult to reconcile with sustained activity. ORGaNICs can be used to explain the complex dynamics of activity, and ORGaNICs can be use to manipulate (as well as maintain) information during a working memory task. The theory provides a means for reading out information from the dynamically varying responses at any point in time, in spite of the complex dynamics. When applied to motor systems, ORGaNICs can be used to convert spatial patterns of premotor activity to temporal profiles of motor activity: different spatial patterns of premotor activity evoke different temporal response dynamics. ORGaNICs offer a novel conceptual framework; Rethinking cortical computation in these terms should have widespread implications, motivating a variety of experiments.

Functional stability in a dynamic network – the role of inhibition

Lecture
Date:
Tuesday, December 18, 2018
Hour: 12:30
Location:
Nella and Leon Benoziyo Building for Brain Research
Prof. Yonatan Loewenstein
|
Department of Neurobiology – ELSC Hebrew University of Jerusalem

According to the synaptic trace theory of memory, activity-induced changes in the pattern of synaptic connections underlie the storage of information for long periods. In this framework, the stability of memory critically depends on the stability of the underlying synaptic connections. Surprisingly however, the excitatory synaptic connections, which constitute most of the synapses in the cortex, are highly volatile in the living brain, which poses a fundamental challenge to the synaptic trace theory. We show that in the balanced cortex, patterns of neural activity are primarily determined by the inhibitory connectivity, despite the fact that most synapses and neurons are excitatory. Similarly, we show that the inhibitory network is more effective in storing memory patterns than the excitatory one. As a result, network activity is robust to ongoing volatility of excitatory synapses, as long as this volatility does not disrupt the balance between excitation and inhibition. We thus hypothesize that inhibitory connectivity, rather than excitatory, controls the maintenance and loss of information over long periods of time in the volatile cortex.

Learning and sleep-dependent dendritic spine plasticity and maintenance

Lecture
Date:
Thursday, December 6, 2018
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Wenbiao Gan
|
Skirball Institute of Biomolecular Medicine, Molecular Neurobiology, Dept of Neuroscience and Physiology, New York University

Learning and sleep-dependent dendritic spine plasticity and maintenance

Lecture
Date:
Thursday, December 6, 2018
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Wenbiao Gan
|
Skirball Institute of Biomolecular Medicine, Molecular Neurobiology, Dept of Neuroscience and Physiology, New York University

Cellular function given parametric variation in the Hodgkin-Huxley model

Lecture
Date:
Tuesday, November 27, 2018
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Shimon Marom
|
Rappaport Faculty of Medicine, Technion, Haifa

How is reliable physiological function maintained in cells despite considerable variability in the values of key parameters of multiple interacting processes that govern that function? I will describe a possible approach to the problem, through analysis of the classic Hodgkin-Huxley formulation of membrane action potential. Although the full Hodgkin-Huxley model is very sensitive to fluctuations that independently occur in its many parameters, the outcome is in fact determined by simple combinations of these parameters along two physiological dimensions: Structural and Kinetic (denoted S and K). The impacts of parametric fluctuations on the dynamics of the system — seemingly complex in the high dimensional representation of the Hodgkin-Huxley model — are tractable when examined within the S-K plane. Experimental validation of the resulting phase diagram is offered, using a bio-synthetic system.

The Inspirational Brain: Human Non-Olfactory Cognition is Phase-Locked with Sniffing

Lecture
Date:
Thursday, November 22, 2018
Hour: 14:00 - 15:00
Location:
Gerhard M.J. Schmidt Lecture Hall
Ofer Perl (PhD Thesis Defense)
|
Noam Sobel Lab, Dept of Neurobiology, WIS

Olfactory stimulus acquisition is perfectly synchronized with inhalation, which tunes neuronal ensembles for incoming information. Because olfaction is an ancient sensory system that provided a template for brain evolution, we hypothesized that this link persisted, and therefore sniffs may tune the brain for acquisition of non-olfactory information as well. To test this, we measured nasal airflow and electroencephalography during various non-olfactory cognitive tasks. We observed that participants spontaneously inhale at non-olfactory cognitive task onset, and that such inhalations shift brain functional network architecture. Concentrating on visuospatial perception, we observed that inhalation drove increased task-related brain activity in specific task-related brain regions, and resulted in improved performance accuracy in the visuospatial task. Thus, mental processes with no link to olfaction are nevertheless phase-locked with sniffing, consistent with the notion of an olfaction-based template in the evolution of human brain function.

Development of Memory Systems in the Human Brain

Lecture
Date:
Tuesday, November 20, 2018
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Noa Ofen
|
Department of Psychology Institute of Gerontology and Merrill Palmer Institute for Child Development Wayne State University, Detroit

Episodic memory – the ability to encode, maintain and retrieve information – is critical for everyday functioning at all ages, yet little is known about the development of episodic memory systems and their brain substrates. In this talk, I will present data from a series of studies with which we begin to identify how brain development underlies changes in episodic memory throughout childhood and adolescence. Using structural MRI data, I will present evidence demonstrating how brain development sets limits on cognitive developmnet. I will show that individual differences in fine structural measures of the hippocampus, a region known to be critical for episodic memory, and the prefrontal cortex (PFC), a region that shows protracted structural development, partially explain age-related improvement in episodic memory. Using functional neuroimaging methods including functional MRI (fMRI) and electrocorticography (ECoG), I will present our ongoing attempts to characterize the neural correlates of episodic memory development. Evidence from fMRI studies suggest that age differences in episodic memory functioning may primarily relate to age differneces in PFC activation and connectivity patterns. Intracranial evidence further underscores the role of the PFC in memory and reveals that spatiotemporal propagation of frontal activity supports memory formation in children. I will highlight the challenges in investigaitons of brain-behavior relations in pediatric populations and discuss how advances in methodologies provide unique opportunities for moving towards a mechanistic understanding of developmental changes.

Neurophysiology of States of Consciousness: From Mechanistic Principles to Novel Diagnostic and Therapeutic Tools

Lecture
Date:
Thursday, November 15, 2018
Hour: 12:30
Location:
Nella and Leon Benoziyo Building for Brain Research
Prof. Jacobo Diego Sitt
|
MD, PhD, HDR INSERM CRN Sorbonne Universities, UPMC Univ Paris 06 ICM Research Center Pitié Salpêtrière Hospital Paris

Uncovering the neural mechanisms that allow conscious access to information is a major challenge of neuroscience. An incomplete list of still open questions include, What are the necessary brain computational properties to permit access to a stream of conscious contents? What is the relationship between conscious perception, self-awareness and multisensory processing of bodily signals? How these processes change when the brain transitions to an ‘unconscious’ state (like sleep, anaesthesia or pathological conditions)? Can we externally trigger state-of-consciousness (SOC) transitions by means of stimulation? In this presentation I will present my work focus in these relevant scientific and clinical questions. I will present our latest developments including different pre-clinical and clinical experimental models (brain-injuries and/or anesthesia), neuroimaging methods (EEG, fMRI or brain/body interactions) and stimulation techniques (tES, auditory/somatosensory/visual stimulation). Overall I will try to demonstrate that the integration of multimodal neural information provides critical information to characterise the state-of-consciousness in physiological and pathological conditions and might help to predict novel optimal therapeutic strategies.

Perception and retinal integration of rod and cone signals in primate

Lecture
Date:
Tuesday, November 13, 2018
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Dr. William Grimes
|
NINDS/NIH

Over the course of a natural day-night cycle, mean luminance levels can span ten log units or more. Mammalian retinas effectively encode visual information over this vast range, in part by utilizing exquisitely sensitive rod photoreceptors in dim conditions and multiple color-variant cone photoreceptors in bright conditions. These visual signals, regardless of origin, must pass through a common set of retinal ganglion cells, thereby creating opportunities for signal interactions. Human perceptual experiments conducted under intermediate lighting conditions reveal constructive and destructive interactions between flickering rod and cone stimuli that are thought to originate in the retina. In support of this hypothesis, we find rod-cone flicker interference in On and Off retinal ganglion cells that project! to magnocellular visual pathways in primates. The dependence of this interference on the frequency and phase of the temporal modulation is similar to that observed in perceptual measurements. Recordings from within the retinal circuitry indicate that rod-cone signal interference reflects a linear combination of kinetically-distinct rod and cone signals upstream of the ganglion cell synaptic inputs. Ultimately, using our empirically-derived data as a foundation, we construct a mathematical model that recapitulates known rod-cone interactions and predicts retinal output in response to a broad range of time-varying rod and cone stimuli.

Pages

All events, 2018

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All events, 2018

Prof. Itzchak Steinberg Memorial Symposium

Conference
Date:
Monday, March 26, 2018
Hour: 08:00
Location:
Dolfi and Lola Ebner Auditorium

Windows to the Brain: Advances in Optical Imaging for Understanding Neural Circuit Function

Conference
Date:
Tuesday, January 16, 2018
Hour: 08:30 - 17:30
Location:
David Lopatie Conference Centre