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"Neuronal Gtf2i-dependent myelination deficits as a novel pathophysiological mechanism in Williams syndrome"
Lecture
Wednesday, December 21, 2016
Hour: 14:00
Location:
Gerhard M.J. Schmidt Lecture Hall
"Neuronal Gtf2i-dependent myelination deficits as a novel pathophysiological mechanism in Williams syndrome"
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
Tuesday, December 20, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Similarity matching: a new principle of neural computation
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
Tuesday, December 13, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Fos-expressing ensembles in operant learned responding for food and drug rewards
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
Thursday, December 8, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Spinal cord injuries and brain reorganisation
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
Thursday, December 1, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
A circuit architecture for angular integration in Drosophila
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
Tuesday, November 29, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Electromagnetic stimulation in neural networks and in the brain
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
Wednesday, November 23, 2016
Hour: 13:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Role of Extracellular Matrix and K+-Cl--Cotransporter 2 in Neuronal Inhibition
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
Tuesday, November 22, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
How human white-matter studies can be improved beyond diffusion imaging:The quantitative MRI perspective
Dr. Aviv Mezer
The Edmond and Lily Safra Center for Brain Sciences (ELSC),
Hebrew University, Jerusalem
Sex differences in the brain: a whole body perspective
Lecture
Tuesday, November 8, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Sex differences in the brain: a whole body perspective
Prof. Greet de Vries
Neuroscience Institute,
Georgia State University
The hundreds of sex differences found in the brain beg the question as to how they develop and what is their function. Factors that cause sex differences in the brain are sex chromosomal gene expression, gonadal hormones, and environmental interactions. Parsimony dictates that these factors act directly on the brain. In fact, available literature on sexual differentiation of the mammalian brain by and large considers just two organs: the gonads and the brain. This perspective, which leaves out all other body parts, misleads us in several ways. First, there is accumulating evidence that all organs are sexually differentiated, and that sex differences in peripheral organs affect the brain. For example, there are sex differences in muscles, adipose tissue, the liver, immune system, gut, kidneys, bladder, and placenta that directly affect the nervous system and behavior. Sex differences may therefore develop in part because brains reside in fundamentally different bodies. This has consequences for brain function as well. Brains may generate different output autonomously, but if they are wired up to different bodies, similar output will have different consequences. To generate similar behaviors, the nervous system may have to compensate by giving different commands. This interaction between body and brain has to be taken into account for a full understanding of the development as well as function of sex differences in the brain. Considering the consequences of this interaction also provides possible explanations for the often remarkable sex differences in neurological and behavioral disorders. These principles will be demonstrated by discussing the development and function of sex differences in vasopressin signaling in brain and body.
Visual perception as retrospective decoding in working memory
Lecture
Tuesday, November 1, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Visual perception as retrospective decoding in working memory
Prof. Misha Tsodyks
Neurobiology Department, WIS
In collaboration with Ning Qian, Stephanie Ding and Chris Cueva
When faced with complex visual scene, observers inspect different parts of a scene sequentially, storing corresponding features in working memory for subsequent integration into a holistic perception. Yet models of perception rarely consider working memory explicitly. We probed processing hierarchy by comparing absolute judgements of single orientations and relative/ordinal judgements between two sequentially presented orientations. We found that lower-level, absolute judgements failed to account for higher-level, relative/ordinal judgements. However, when ordinal judgement was used to retrospectively decode memory representations of absolute orientations, striking aspects of absolute judgements, including their correlation and forward/backward aftereffects, were explained. We suggest that the brain prioritizes decoding of more useful, higher-level features, which are more invariant and categorical and thus easier to specify and maintain in noisy working memory, and that more-reliable higher-level decoding.
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Electromagnetic stimulation in neural networks and in the brain
Lecture
Tuesday, November 29, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Electromagnetic stimulation in neural networks and in the brain
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
Wednesday, November 23, 2016
Hour: 13:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Role of Extracellular Matrix and K+-Cl--Cotransporter 2 in Neuronal Inhibition
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
Tuesday, November 22, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
How human white-matter studies can be improved beyond diffusion imaging:The quantitative MRI perspective
Dr. Aviv Mezer
The Edmond and Lily Safra Center for Brain Sciences (ELSC),
Hebrew University, Jerusalem
Sex differences in the brain: a whole body perspective
Lecture
Tuesday, November 8, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Sex differences in the brain: a whole body perspective
Prof. Greet de Vries
Neuroscience Institute,
Georgia State University
The hundreds of sex differences found in the brain beg the question as to how they develop and what is their function. Factors that cause sex differences in the brain are sex chromosomal gene expression, gonadal hormones, and environmental interactions. Parsimony dictates that these factors act directly on the brain. In fact, available literature on sexual differentiation of the mammalian brain by and large considers just two organs: the gonads and the brain. This perspective, which leaves out all other body parts, misleads us in several ways. First, there is accumulating evidence that all organs are sexually differentiated, and that sex differences in peripheral organs affect the brain. For example, there are sex differences in muscles, adipose tissue, the liver, immune system, gut, kidneys, bladder, and placenta that directly affect the nervous system and behavior. Sex differences may therefore develop in part because brains reside in fundamentally different bodies. This has consequences for brain function as well. Brains may generate different output autonomously, but if they are wired up to different bodies, similar output will have different consequences. To generate similar behaviors, the nervous system may have to compensate by giving different commands. This interaction between body and brain has to be taken into account for a full understanding of the development as well as function of sex differences in the brain. Considering the consequences of this interaction also provides possible explanations for the often remarkable sex differences in neurological and behavioral disorders. These principles will be demonstrated by discussing the development and function of sex differences in vasopressin signaling in brain and body.
Visual perception as retrospective decoding in working memory
Lecture
Tuesday, November 1, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Visual perception as retrospective decoding in working memory
Prof. Misha Tsodyks
Neurobiology Department, WIS
In collaboration with Ning Qian, Stephanie Ding and Chris Cueva
When faced with complex visual scene, observers inspect different parts of a scene sequentially, storing corresponding features in working memory for subsequent integration into a holistic perception. Yet models of perception rarely consider working memory explicitly. We probed processing hierarchy by comparing absolute judgements of single orientations and relative/ordinal judgements between two sequentially presented orientations. We found that lower-level, absolute judgements failed to account for higher-level, relative/ordinal judgements. However, when ordinal judgement was used to retrospectively decode memory representations of absolute orientations, striking aspects of absolute judgements, including their correlation and forward/backward aftereffects, were explained. We suggest that the brain prioritizes decoding of more useful, higher-level features, which are more invariant and categorical and thus easier to specify and maintain in noisy working memory, and that more-reliable higher-level decoding.
Neurodevelopmental disorders from basic science to novel therapeutic approaches
Lecture
Sunday, October 9, 2016
Hour: 10:00
Location:
Gerhard M.J. Schmidt Lecture Hall
Neurodevelopmental disorders from basic science to novel therapeutic approaches
Dr. Yehezkel (Hezi) Sztainberg
Dept of Molecular and Human Genetics, Baylor College of Medicine
and The Jan and Dan Duncan Neurological Research Institute,
Texas Children’s Hospital, Houston TX
Neurodevelopmental disorders encompass a wide range of childhood-onset medical conditions caused by different genetic mutations and interaction with environmental factors, affect ~2% of the population, and are a leading cause of intellectual disability and autism spectrum disorder. Evidence is accumulating that either loss or gain in dosage of proteins involved in cognitive and behavioural processes can be deleterious to the nervous system by causing a failure in the ability to maintain neuronal homeostasis. My studies are focused on the MECP2 duplication syndrome, one of the most common genomic rearrangements in males, characterized by autism, intellectual disability, motor dysfunction, anxiety, epilepsy, recurrent respiratory tract infections and early death. To determine whether the phenotypes of MECP2 duplication are reversible upon normalization of MeCP2 levels, I first generated and characterized a new mouse model that over-expresses a conditional allele of Mecp2 that could be deleted in the adult animal (Nature 2015). Upon normalization of MeCP2 in adult symptomatic mice, several phenotypes were rescued at the behavioral, physiological, and molecular levels. Next, I reduced MeCP2 using an antisense oligonucleotide (ASO) strategy, which has greater translational potential. I found that ASO treatment induced a broad phenotypic rescue in adult symptomatic MECP2 duplication mice, abolished abnormal EEG discharges and behavioral seizures, and corrected abnormal gene expression in the hippocampus. I am currently characterizing a novel “humanized” mouse model of MECP2 duplication syndrome that will precisely mimic the human condition by having two copies of human MECP2 and no copies of the mouse gene. These mice will serve as the ideal model for preclinical tests as they represent the closest construct validity model for the human condition. In addition, I am generating and characterizing neurons and cortical spheroids induced from patients’ derived pluripotent stem cells (iPSCs).
Encoding of action by the Purkinje cells of the cerebellum
Lecture
Sunday, September 25, 2016
Hour: 14:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Encoding of action by the Purkinje cells of the cerebellum
Prof. Reza Shadmehr
Biomedical Engineering and Neuroscience
Johns Hopkins University
The curious case of Dr. Scoville and Mr. Molaison or: How the famous amnesic patient H.M. is not forgotten and stirs much unrest in the neuroscience community
Lecture
Tuesday, September 20, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
The curious case of Dr. Scoville and Mr. Molaison or: How the famous amnesic patient H.M. is not forgotten and stirs much unrest in the neuroscience community
Prof. Yadin Dudai
Department of Neurobiology, WIS
The contribution of ventromedial prefrontal cortex to memory and decision making
Lecture
Sunday, September 18, 2016
Hour: 12:30
Location:
Nella and Leon Benoziyo Building for Brain Research
The contribution of ventromedial prefrontal cortex to memory and decision making
Prof. Asaf Gilboa
Rotman Research Institute at Baycrest Health Sciences and Dept of Psychology, University of Toronto
The Self and the Friend in Space
Lecture
Tuesday, September 6, 2016
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
The Self and the Friend in Space
Dr. Pia Rotshtein
School of Psychology,
Birmingham University Imaging Centre,
University of Birmingham UK
Understanding the Self has fascinated artists, writers, philosophers and psychologist for generation. In the past two decades cognitive and neurocognitive tools have been applied to the study of the Self. The talk will present research on the Self and the Friend. Not surprisingly, it is consistently found that our brain prioritize the Self. For example, deciding whether a face looks to the left or right is faster on one’s own face than on a face of a friend. This prioritization transcend time, showing similar prioritization to one’s face in the past as in the present. Lesions to the fusiform gyrus hinders Self facilitation, while lesions to lateral frontal cortices amplifies it. Associating a simple geometric shape to oneself is done much more efficiently than to a stranger an effect that is mediated via the left STS, medial and lateral frontal cortices. Participants are also better at judging a perspective of an avatar if it is tagged as them than as a stranger. But in all these studies the Friend is also prioritized relative to a stranger. Why is the friend prioritized, is it because it is relevant, or because it is liked? In a simple shape-identity matching task, we manipulated orthogonally the valence and relevance of familiar identities. We found that prioritization is given based on relevance and valence in Western culture, but primarily based on valance in Asian cultures. Using spatial maps to represent the social space, we observed consistent representation of social relations as physical distances. Physical distance between identities was affected by the valence and relevance factors, though this was modulated by the participants’ culture. Finally, presenting participants with incongruent spatial maps of their social relations, resulted in increase and decrease responses in a large network of regions including the Amygdala and superior temporal structure known to play a rule in social cognition. Taken together this body of work highlight neurocognitive mechanism by which our brain prioritize information based on social rules.
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