All events, 2016

Molecular classification of cells in the mouse brain revealed by single-cell RNAseq

Lecture
Date:
Wednesday, December 28, 2016
Hour: 09:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Dr. Amit Zeisel
|
Molecular Neurobiology, MBB, Karolinska Institute, Sweden

The mammalian central nervous system is arguably the most complex system studied in biology. Normal function of the brain relies on the assembly of a diverse set of cell-types, including most prominently neurons, but also glial cells and vasculature. We developed and applied large-scale single-cell RNA sequencing for unbiased molecular cell-type classification in various regions of the mouse brain. I will describe our initial work on the somatosensory cortex and hippocampus CA1, and later give examples about heterogeneity in the oligodendrocyte lineage across the CNS. These results and our ongoing efforts demonstrate how detailed information about cell-types in the brain may contribute to understand brain function.

Stimulus-specific adaptation in auditory cortex: models, data, and surprises

Lecture
Date:
Tuesday, December 27, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Eli Nelken
|
ELSC and the Dept of Neurobiology Silberman Institute of Life Sciences, Hebrew University, Jerusalem

Stimulus specific adaptation (SSA) is the decrease in the responses to a repeated sound which generalizes only partially to other sounds. I discuss our recent attempts to study the mechanisms underlying SSA. First, using well-controlled broadband stimuli, we show that responses in IC and MGB roughly agree with a simple model of input adaptation leading to SSA, while in auditory cortex neurons adapt in a manner that more stimulus-specific. Second, I will show our attempts to study the spatial organization of SSA, as well as the finer property of deviance sensitivity, in mouse auditory cortex, as well as our preliminary data on the role of inhibitory interneurons in shaping cortical SSA.

"Neuronal Gtf2i-dependent myelination deficits as a novel pathophysiological mechanism in Williams syndrome"

Lecture
Date:
Wednesday, December 21, 2016
Hour: 14:00
Location:
Gerhard M.J. Schmidt Lecture Hall
Dr. Boaz Barak
|
Brain and Cognitive Sciences, McGovern Institute, MIT

Williams syndrome (WS) is a neurodevelopmental disorder caused by a heterozygous microdeletion of about 26 genes from chromosomal region 7q11.23, characterized by hypersociability and unique neurocognitive abnormalities. Of those deleted, general transcription factor II-i (Gtf2i), has been shown to affect hypersociability in WS, although the cell type and neural circuitry critical for the hypersociability are poorly understood. To dissect neural circuitry related to hypersociability in WS and to characterize the neuron-autonomous role of Gtf2i we conditionally knockedout Gtf2i in forebrain excitatory neurons and found this recapitulate WS features, including increased sociability and anxiety and neuroanatomical defects. Unexpectedly, we found that in the mutant mouse cortex 70% of the significantly downregulated genes were involved in myelination, together with a reduction in mature oligodendrocyte cells number, disrupted myelin ultrastructure and fine motor deficits. Analyzing the transcriptome in human frontal cortex, we found similar downregulation of myelination-related genes, suggesting a novel pathophysiological mechanism in WS, based on neuron-oligodendrocytes signaling deficits. Overall, our data detail the cellular processes that may lead to the WS typical phenotype and developmental abnormalities, and suggest new paths to explore and treat WS, as well as social and cognitive abnormalities.

Similarity matching: a new principle of neural computation

Lecture
Date:
Tuesday, December 20, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Dmitri "Mitya" Chklovskii
|
Simons Foundation and NYU Medical Center

Abundance of recently obtained datasets on brain structure (connectomics) and function (neuronal population activity) calls for a normative theory of neural computation. In the conventional, so-called, reconstruction approach to neural computation, population activity is thought to represent the stimulus. Instead, we propose that the similarity of population activity matches the similarity of the stimuli under certain constraints. From this similarity matching principle, we derive online algorithms that can account for both structural and functional observations. Bio: Dmitri "Mitya" Chklovskii is Group Leader for Neuroscience at the Simons Foundation's new Flatiron Institute in New York City. He received a PhD in Theoretical Physics from MIT and was a Junior Fellow at the Harvard Society of Fellows. He switched from physics to neuroscience at the Salk Institute and founded the first theoretical neuroscience group at Cold Spring Harbor Laboratory in 1999, where he was an Assistant and then Associate Professor. From 2007 to 2014 he was a Group Leader at Janelia Farm where he led a team that assembled the largest-ever connectome. His group develops software for experimental data analysis and constructs normative theories of neural computation.

Fos-expressing ensembles in operant learned responding for food and drug rewards

Lecture
Date:
Tuesday, December 13, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Dr. Bruce Hope
|
National Institute on Drug Abuse, IRP/NIH

We assess the neural mechanisms of learned associations in operant-learned behaviors. These learned associations or memories involve complex sets of highly specific information that must be stored with a high degree of resolution. In contrast, most studies to date examined low resolution neural mechanisms in whole brain areas, cell types or randomly selected neurons regardless of whether they were activated and participated in the behavior. Instead, high resolution memories are thought to be stored by alterations induced selectively within sparsely distributed patterns of neurons, called neuronal ensembles, that are selectively activated by cues relevant to the memory. We developed the Daun02 inactivation procedure with transgenic FosLacZ rats to demonstrate that different patterns of strongly activated Fos-expressing ensembles mediate different memories. Since these ensembles encode the memory, we developed methods that use (1) FACS to discover multiple molecular alterations and (2) FosGFP transgenic rats to discover multiple electrophysiological alterations that are induced only within Fos-expressing neurons. We have since developed a Fos-Tet-Cre transgenic rat system that allows us to selectively manipulate these alterations within Fos-expressing ensembles to assess whether they play a causal role in operant learned behaviors. It is our hope that a focus on the behaviorally activated ensembles that store the memories will permit more focused novel treatments of behavioral disorders.

Spinal cord injuries and brain reorganisation

Lecture
Date:
Thursday, December 8, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof Neeraj Jain
|
National Brain Research Centre, Manesar, Haryana, India

Adult mammalian brains show remarkable plasticity in response to deafferentations due to injuries. Lesions of dorsal columns of the spinal cord at cervical levels deafferent sensory inputs from parts of the body below the level of the lesion. Chronic dorsal column injuries in monkeys result in expansion of intact chin inputs into the deafferented hand regions of the primary and secondary somatosensory cortex (area 3 and area S2), ventroposterior lateral nucleus of the thalamus and cuneate nucleus of the brain stem. Our recent evidence suggests that the key plastic change takes place in the brain stem nuclei, perhaps due to axonal growth from the trigeminal nucleus into the cuneate nucleus. This reorganization is then propagated upstream resulting a brain-wide reorganization.

A circuit architecture for angular integration in Drosophila

Lecture
Date:
Thursday, December 1, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Gaby Maimon
|
Laboratory of Integrative Brain Function The Rockefeller University

Mammalian brains store and update quantitative internal variables. Primates and rodents, for example, have an internal sense of whether they are 1 or 10 meters away from a landmark and whether a ripe fruit is twice or four times as appetizing as a less ripe counterpart. Such quantitative internal signals are the basis of cognitive function, however, our understanding of how the brain stores and updates these variables remains fragmentary. In this talk, I will discuss imaging and perturbation experiments in tethered, walking Drosophila. The goal of these experiments is to determine how internal variables are calculated by the tiny Drosophila brain and how these variables influence behavior. Specifically, in the Drosophila central complex a set of heading neurons have been described, whose activity tracks the fly’s orientation, similar to head direction cells in rodents. However, the circuit architecture that gives rise to these orientation tracking properties remains largely unknown in any species. I will describe a set of clockwise- and counterclockwise-shifting neurons whose wiring and calcium dynamics provide a means to rotate the heading system’s angular estimate over time. Shifting neurons are required for the heading system to properly track the fly's movements in the dark, and, their stimulation induces a rotation of the heading signal in the expected direction and by the expected amount. The central features of this circuit are analogous to models proposed for head-direction cells in rodents and may thus inform how neural systems, in general, perform addition.

Electromagnetic stimulation in neural networks and in the brain

Lecture
Date:
Tuesday, November 29, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Elisha Moses
|
Dept of Physics of Complex Systems, WIS

External stimulation of the brain is emerging as a novel methodology for treatment of mental illness and possibly also for cognitive enhancement. Electric and magnetic and even ultrasound stimulation of neurons have all shown to be effective in eliciting brain activation, but the actual effect on a single neuron remains unclear. Combining experiments on excitation in neuronal cultures, animals and humans with theory and numerical simulations, we have been able to unravel the contribution of electric and of magnetic pulses delivered to the brain. We show that today’s magnetic stimulation techniques do not optimally target neurons in the brain, and that they can be considerably enhanced with simple technical modifications involving rotating magnetic fields and prolonged pulse durations. We end by suggesting practical clinical trials for the near future.

Role of Extracellular Matrix and K+-Cl--Cotransporter 2 in Neuronal Inhibition

Lecture
Date:
Wednesday, November 23, 2016
Hour: 13:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Dr. Tushar Yelhekar (Postdoc Candidate)
|
Integrative Medical Biology (IMB) Umea University, Sweden

How human white-matter studies can be improved beyond diffusion imaging:The quantitative MRI perspective

Lecture
Date:
Tuesday, November 22, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Dr. Aviv Mezer
|
The Edmond and Lily Safra Center for Brain Sciences (ELSC), Hebrew University, Jerusalem

Pages

All events, 2016

Molecular classification of cells in the mouse brain revealed by single-cell RNAseq

Lecture
Date:
Wednesday, December 28, 2016
Hour: 09:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Dr. Amit Zeisel
|
Molecular Neurobiology, MBB, Karolinska Institute, Sweden

The mammalian central nervous system is arguably the most complex system studied in biology. Normal function of the brain relies on the assembly of a diverse set of cell-types, including most prominently neurons, but also glial cells and vasculature. We developed and applied large-scale single-cell RNA sequencing for unbiased molecular cell-type classification in various regions of the mouse brain. I will describe our initial work on the somatosensory cortex and hippocampus CA1, and later give examples about heterogeneity in the oligodendrocyte lineage across the CNS. These results and our ongoing efforts demonstrate how detailed information about cell-types in the brain may contribute to understand brain function.

Stimulus-specific adaptation in auditory cortex: models, data, and surprises

Lecture
Date:
Tuesday, December 27, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Eli Nelken
|
ELSC and the Dept of Neurobiology Silberman Institute of Life Sciences, Hebrew University, Jerusalem

Stimulus specific adaptation (SSA) is the decrease in the responses to a repeated sound which generalizes only partially to other sounds. I discuss our recent attempts to study the mechanisms underlying SSA. First, using well-controlled broadband stimuli, we show that responses in IC and MGB roughly agree with a simple model of input adaptation leading to SSA, while in auditory cortex neurons adapt in a manner that more stimulus-specific. Second, I will show our attempts to study the spatial organization of SSA, as well as the finer property of deviance sensitivity, in mouse auditory cortex, as well as our preliminary data on the role of inhibitory interneurons in shaping cortical SSA.

"Neuronal Gtf2i-dependent myelination deficits as a novel pathophysiological mechanism in Williams syndrome"

Lecture
Date:
Wednesday, December 21, 2016
Hour: 14:00
Location:
Gerhard M.J. Schmidt Lecture Hall
Dr. Boaz Barak
|
Brain and Cognitive Sciences, McGovern Institute, MIT

Williams syndrome (WS) is a neurodevelopmental disorder caused by a heterozygous microdeletion of about 26 genes from chromosomal region 7q11.23, characterized by hypersociability and unique neurocognitive abnormalities. Of those deleted, general transcription factor II-i (Gtf2i), has been shown to affect hypersociability in WS, although the cell type and neural circuitry critical for the hypersociability are poorly understood. To dissect neural circuitry related to hypersociability in WS and to characterize the neuron-autonomous role of Gtf2i we conditionally knockedout Gtf2i in forebrain excitatory neurons and found this recapitulate WS features, including increased sociability and anxiety and neuroanatomical defects. Unexpectedly, we found that in the mutant mouse cortex 70% of the significantly downregulated genes were involved in myelination, together with a reduction in mature oligodendrocyte cells number, disrupted myelin ultrastructure and fine motor deficits. Analyzing the transcriptome in human frontal cortex, we found similar downregulation of myelination-related genes, suggesting a novel pathophysiological mechanism in WS, based on neuron-oligodendrocytes signaling deficits. Overall, our data detail the cellular processes that may lead to the WS typical phenotype and developmental abnormalities, and suggest new paths to explore and treat WS, as well as social and cognitive abnormalities.

Similarity matching: a new principle of neural computation

Lecture
Date:
Tuesday, December 20, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Dmitri "Mitya" Chklovskii
|
Simons Foundation and NYU Medical Center

Abundance of recently obtained datasets on brain structure (connectomics) and function (neuronal population activity) calls for a normative theory of neural computation. In the conventional, so-called, reconstruction approach to neural computation, population activity is thought to represent the stimulus. Instead, we propose that the similarity of population activity matches the similarity of the stimuli under certain constraints. From this similarity matching principle, we derive online algorithms that can account for both structural and functional observations. Bio: Dmitri "Mitya" Chklovskii is Group Leader for Neuroscience at the Simons Foundation's new Flatiron Institute in New York City. He received a PhD in Theoretical Physics from MIT and was a Junior Fellow at the Harvard Society of Fellows. He switched from physics to neuroscience at the Salk Institute and founded the first theoretical neuroscience group at Cold Spring Harbor Laboratory in 1999, where he was an Assistant and then Associate Professor. From 2007 to 2014 he was a Group Leader at Janelia Farm where he led a team that assembled the largest-ever connectome. His group develops software for experimental data analysis and constructs normative theories of neural computation.

Fos-expressing ensembles in operant learned responding for food and drug rewards

Lecture
Date:
Tuesday, December 13, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Dr. Bruce Hope
|
National Institute on Drug Abuse, IRP/NIH

We assess the neural mechanisms of learned associations in operant-learned behaviors. These learned associations or memories involve complex sets of highly specific information that must be stored with a high degree of resolution. In contrast, most studies to date examined low resolution neural mechanisms in whole brain areas, cell types or randomly selected neurons regardless of whether they were activated and participated in the behavior. Instead, high resolution memories are thought to be stored by alterations induced selectively within sparsely distributed patterns of neurons, called neuronal ensembles, that are selectively activated by cues relevant to the memory. We developed the Daun02 inactivation procedure with transgenic FosLacZ rats to demonstrate that different patterns of strongly activated Fos-expressing ensembles mediate different memories. Since these ensembles encode the memory, we developed methods that use (1) FACS to discover multiple molecular alterations and (2) FosGFP transgenic rats to discover multiple electrophysiological alterations that are induced only within Fos-expressing neurons. We have since developed a Fos-Tet-Cre transgenic rat system that allows us to selectively manipulate these alterations within Fos-expressing ensembles to assess whether they play a causal role in operant learned behaviors. It is our hope that a focus on the behaviorally activated ensembles that store the memories will permit more focused novel treatments of behavioral disorders.

Spinal cord injuries and brain reorganisation

Lecture
Date:
Thursday, December 8, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof Neeraj Jain
|
National Brain Research Centre, Manesar, Haryana, India

Adult mammalian brains show remarkable plasticity in response to deafferentations due to injuries. Lesions of dorsal columns of the spinal cord at cervical levels deafferent sensory inputs from parts of the body below the level of the lesion. Chronic dorsal column injuries in monkeys result in expansion of intact chin inputs into the deafferented hand regions of the primary and secondary somatosensory cortex (area 3 and area S2), ventroposterior lateral nucleus of the thalamus and cuneate nucleus of the brain stem. Our recent evidence suggests that the key plastic change takes place in the brain stem nuclei, perhaps due to axonal growth from the trigeminal nucleus into the cuneate nucleus. This reorganization is then propagated upstream resulting a brain-wide reorganization.

A circuit architecture for angular integration in Drosophila

Lecture
Date:
Thursday, December 1, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Gaby Maimon
|
Laboratory of Integrative Brain Function The Rockefeller University

Mammalian brains store and update quantitative internal variables. Primates and rodents, for example, have an internal sense of whether they are 1 or 10 meters away from a landmark and whether a ripe fruit is twice or four times as appetizing as a less ripe counterpart. Such quantitative internal signals are the basis of cognitive function, however, our understanding of how the brain stores and updates these variables remains fragmentary. In this talk, I will discuss imaging and perturbation experiments in tethered, walking Drosophila. The goal of these experiments is to determine how internal variables are calculated by the tiny Drosophila brain and how these variables influence behavior. Specifically, in the Drosophila central complex a set of heading neurons have been described, whose activity tracks the fly’s orientation, similar to head direction cells in rodents. However, the circuit architecture that gives rise to these orientation tracking properties remains largely unknown in any species. I will describe a set of clockwise- and counterclockwise-shifting neurons whose wiring and calcium dynamics provide a means to rotate the heading system’s angular estimate over time. Shifting neurons are required for the heading system to properly track the fly's movements in the dark, and, their stimulation induces a rotation of the heading signal in the expected direction and by the expected amount. The central features of this circuit are analogous to models proposed for head-direction cells in rodents and may thus inform how neural systems, in general, perform addition.

Electromagnetic stimulation in neural networks and in the brain

Lecture
Date:
Tuesday, November 29, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Elisha Moses
|
Dept of Physics of Complex Systems, WIS

External stimulation of the brain is emerging as a novel methodology for treatment of mental illness and possibly also for cognitive enhancement. Electric and magnetic and even ultrasound stimulation of neurons have all shown to be effective in eliciting brain activation, but the actual effect on a single neuron remains unclear. Combining experiments on excitation in neuronal cultures, animals and humans with theory and numerical simulations, we have been able to unravel the contribution of electric and of magnetic pulses delivered to the brain. We show that today’s magnetic stimulation techniques do not optimally target neurons in the brain, and that they can be considerably enhanced with simple technical modifications involving rotating magnetic fields and prolonged pulse durations. We end by suggesting practical clinical trials for the near future.

Role of Extracellular Matrix and K+-Cl--Cotransporter 2 in Neuronal Inhibition

Lecture
Date:
Wednesday, November 23, 2016
Hour: 13:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Dr. Tushar Yelhekar (Postdoc Candidate)
|
Integrative Medical Biology (IMB) Umea University, Sweden

How human white-matter studies can be improved beyond diffusion imaging:The quantitative MRI perspective

Lecture
Date:
Tuesday, November 22, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Dr. Aviv Mezer
|
The Edmond and Lily Safra Center for Brain Sciences (ELSC), Hebrew University, Jerusalem

Pages

All events, 2016

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All events, 2016

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