All events, All years

Oxytocin for autism? Insights from genetic mouse models

Lecture
Date:
Thursday, February 23, 2017
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Olga Penagarikano
|
Dept of Pharmacology, School of Medicine University of the Basque Country, Leioa, Spain

Autism Spectrum Disorder is a heterogeneous condition characterized by deficits in social interactions and repetitive behaviors/restricted interests. Mouse models based on human disease-causing mutations provide the potential for understanding associated neuropathology and developing targeted treatments. Genetic, neurobiological and imaging data provide convergent evidence for the CNTNAP2 gene as a risk factor for autism and other developmental disorders. First, I will present data from my postdoctoral work demonstrating construct, face and predictive validity of a mouse knockout for the Cntnap2 gene, providing a tool for mechanistic and therapeutic research. In fact, through an in vivo drug screen in this model we found that administration of the neuropeptide oxytocin dramatically improves social deficits. Strikingly, reduced neuropeptide levels in this model seemed to account for the behavioral response. Last, I will present ongoing work in my lab evaluating the oxytocin system and related neurotransmitters in this model. Alterations in the oxytocin system and/or dysfunction in its related biological processes could potentially be more common in autism than previously anticipated.

A Circuits First Approach to Mental Illness

Lecture
Date:
Tuesday, February 21, 2017
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Amit Etkin
|
Dept of Psychiatry and Behavioral Sciences Stanford Neurosciences Institute, Stanford University and Investigator, Sierra-Pacific MIRECC, Palo Alto VA

The interplay between learning systems and their impact on long-term declarative memory

Lecture
Date:
Tuesday, February 14, 2017
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Dr. Avi Mendelsohn
|
Dept of Neurobiology, Faculty of Life Sciences, University of Haifa

Nonlinear coherences among multiple time-series:Use of MRI data to identify brain temporal organization and directionality of information flow

Lecture
Date:
Thursday, February 9, 2017
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Gadi Goelman
|
Human Biology Research Center, Dept of Nuclear Medicine, Hadassah Medical Center, Jerusalem

Coherences and time-lags are commonly used to infer directionality of information flow in electrophysiology EEG, MEG and MRI. Current approaches, however, enable to calculate only pairwise (linear) coherences. I will describe a novel high-order statistical framework to calculate coherences among multiple coupled time-series. The full mathematical expressions for 4 time-series will be described and its validity will be demonstrated by computer simulations of the Kuramoto model. Quartets of time-series (i.e. brain regions) will be defined as linear, nonlinear or of higher (>4) order. By this, whole systems (e.g. motor, visual) will be categorized as linear or nonlinear. Based on the assumption that MRI phase delays are associated with time of information flow, the temporal hierarchy and directionality of several brain systems will be described. To fully categorize the information flow within 4th order networks, I will introduce the concept of Motifs that describes the pathway trajectories within networks. The advantages of motifs in brain research will be demonstrated by comparing motifs of the ventral versus the dorsal streams systems and in males versus females.

Why Sensory Deprivation and High Plasticity may lead to Hallucinations and Synaesthesia:A Computational Perspective

Lecture
Date:
Tuesday, February 7, 2017
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Dr. Oren Shriki
|
Dept of Cognitive and Brain Sciences Ben-Gurion University

Recurrent connections are abundant in cortical circuitry but their functional role has been the subject of intense debates. The talk will present a computational approach to investigate the role of recurrent connections in the context of sensory processing. Specifically, I will describe a neural network model in which the recurrent connections evolve according to concrete learning rules that optimize the information representation of the network. Interestingly, these networks tend to operate near a "critical" point in their dynamics, namely close to a phase of "hallucinations", in which non-trivial spontaneous patterns of activity evolve even without structured input. Various scenarios, such as attenuation of the external inputs or increased plasticity, can lead the network to cross the border into the hallucinatory phase. The theory will be illustrated through applications to a model of a visual hypercolumn, a model of tinnitus and a model of synaesthesia. References: Shriki O. and Yellin D., Optimal Information Representation and Criticality in an Adaptive Sensory Recurrent Neural Network. PLoS Computational Biology 12(2): e1004698. doi:10.1371/journal.pcbi.1004698, 2016 Shriki O., Sadeh Y. and Ward J., The Emergence of Synaesthesia in a Neuronal Network Model via Changes in Perceptual Sensitivity and Plasticity. PLoS Computational Biology 12(7): e1004959. doi:10.1371/journal.pcbi.1004959, 2016.

Cellular substrates for network information processing in hippocampal CA1

Lecture
Date:
Thursday, February 2, 2017
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Dr. Alessio Attardo
|
Dept of Stress Neurobiology and Neurogenetics Max Planck Institute of Psychiatry, Munich

From Single Nuclei RNA-Sequencing to Dynamics of Neuronal Regeneration

Lecture
Date:
Sunday, January 29, 2017
Hour: 11:00
Location:
Gerhard M.J. Schmidt Lecture Hall
Dr. Naomi Habib
|
Postdoctoral Fellow, Feng Zhang and Aviv Regev Labs Broad Institute of MIT and Harvard and McGovern Institute for Brain Research at MIT

Throughout adult life, adult neuronal stem cells (NSCs) continuously generate neurons in discrete brain regions. I am interested in harnessing this natural regenerative process for repairing the diseased and aging brain. To effectively use this regenerative capacity in a clinical setting requires first an advanced understanding of NSCs, adult neurogenesis and neuronal regeneration during neurodegenerative diseases and aging. Study of these areas, however, is challenging, as it requires profiling rare continuous processes in the adult brain. To this end, I developed sNuc-Seq, a method for profiling RNA in complex tissues with single nuclei resolution by RNA-sequencing, and Div-Seq, for profiling RNA in individual dividing cells. I applied sNuc-Seq to study the adult hippocampus brain region, revealing new cell-type specific and spatial expression patterns. I then applied Div-Seq to track transcriptional dynamics of newborn neurons within the adult hippocampal neurogenic region and to identify and profile rare newborn GABAergic neurons in the adult spinal cord. I am currently developing follow-up technologies to sNuc-Seq and applying them to study the cross-talk between neurons, NSCs, glia and immune cells during neurodegenerative diseases and its role in inhibiting or promoting regeneration. I will continue to work towards advancing our ability to mitigate and even reverse neurodegenerative disease and age-related pathologies. Incorporating in my work techniques from molecular neuroscience, single cell genomics, genome engineering and computational biology.

Reverse-engineering the sense of touch in mice

Lecture
Date:
Thursday, January 26, 2017
Hour: 12:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Samuel Andrew Hires
|
Dept of Neurobiology, University of Southern California, Los Angeles

Touch is vital for many human and animal behaviors, but our understanding of it lags other senses. We have deployed a suite of techniques to dissect mechanisms of touch perception in the mouse, from the biophysics of whisker bending to optogenetic manipulation of specific cortical circuits. I will present our recent work exploring how circuits of primary somatosensory cortex process sensory and motor signals to create a neural representation of tactile features during whisker-based object exploration.

Reverse-engineering the sense of touch in mice

Lecture
Date:
Tuesday, January 24, 2017
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Samuel Andrew Hires
|
Dept of Neurobiology University of Southern California, Los Angeles

Touch is vital for many human and animal behaviors, but our understanding of it lags other senses. We have deployed a suite of techniques to dissect mechanisms of touch perception in the mouse, from the biophysics of whisker bending to optogenetic manipulation of specific cortical circuits. I will present our recent work exploring how circuits of primary somatosensory cortex process sensory and motor signals to create a neural representation of tactile features during whisker-based object exploration.

Towards a multi-scale quantification of the structure and function of the neurovascular interface

Lecture
Date:
Tuesday, January 17, 2017
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Dr. Pablo Blinder
|
Dept of Neurobiology, Faculty of Life Sciences, Tel Aviv University

Abstract: Proper brain function depends on the intricate interface between neurons, astrocytes and the nearby blood vessels that supply then with oxygen and nutrients. Coupling between neuronal activity and local vascular responses represent both a fundamental physiological process and also underpins the mechanism behind BOLD-imaging techniques. We aim to systematically map the structure-function organization of this interface and use this knowledge as morphological framework to interpret neurovascular dynamics. At the system level, we find a puzzling lack of spatial organization between neuronal units of the lemniscal pathway and the surrounding vasculature. I will share these findings and describe our current efforts to map the neuro-vascular microcircuitry. To understand whether neurons wire with some preference into the vasculature, we started to simulate the expected “random" statistics for this morphological interface. In addition, I will share preliminary data showing a differential neuronal response to surgically induced hypo- and hyper-perfusion conditions; suggest a potential modulation role of systemic pressure on neuronal activity.

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Cellular substrates for network information processing in hippocampal CA1

Lecture
Date:
Thursday, February 2, 2017
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Dr. Alessio Attardo
|
Dept of Stress Neurobiology and Neurogenetics Max Planck Institute of Psychiatry, Munich

From Single Nuclei RNA-Sequencing to Dynamics of Neuronal Regeneration

Lecture
Date:
Sunday, January 29, 2017
Hour: 11:00
Location:
Gerhard M.J. Schmidt Lecture Hall
Dr. Naomi Habib
|
Postdoctoral Fellow, Feng Zhang and Aviv Regev Labs Broad Institute of MIT and Harvard and McGovern Institute for Brain Research at MIT

Throughout adult life, adult neuronal stem cells (NSCs) continuously generate neurons in discrete brain regions. I am interested in harnessing this natural regenerative process for repairing the diseased and aging brain. To effectively use this regenerative capacity in a clinical setting requires first an advanced understanding of NSCs, adult neurogenesis and neuronal regeneration during neurodegenerative diseases and aging. Study of these areas, however, is challenging, as it requires profiling rare continuous processes in the adult brain. To this end, I developed sNuc-Seq, a method for profiling RNA in complex tissues with single nuclei resolution by RNA-sequencing, and Div-Seq, for profiling RNA in individual dividing cells. I applied sNuc-Seq to study the adult hippocampus brain region, revealing new cell-type specific and spatial expression patterns. I then applied Div-Seq to track transcriptional dynamics of newborn neurons within the adult hippocampal neurogenic region and to identify and profile rare newborn GABAergic neurons in the adult spinal cord. I am currently developing follow-up technologies to sNuc-Seq and applying them to study the cross-talk between neurons, NSCs, glia and immune cells during neurodegenerative diseases and its role in inhibiting or promoting regeneration. I will continue to work towards advancing our ability to mitigate and even reverse neurodegenerative disease and age-related pathologies. Incorporating in my work techniques from molecular neuroscience, single cell genomics, genome engineering and computational biology.

Reverse-engineering the sense of touch in mice

Lecture
Date:
Thursday, January 26, 2017
Hour: 12:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Samuel Andrew Hires
|
Dept of Neurobiology, University of Southern California, Los Angeles

Touch is vital for many human and animal behaviors, but our understanding of it lags other senses. We have deployed a suite of techniques to dissect mechanisms of touch perception in the mouse, from the biophysics of whisker bending to optogenetic manipulation of specific cortical circuits. I will present our recent work exploring how circuits of primary somatosensory cortex process sensory and motor signals to create a neural representation of tactile features during whisker-based object exploration.

Reverse-engineering the sense of touch in mice

Lecture
Date:
Tuesday, January 24, 2017
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. Samuel Andrew Hires
|
Dept of Neurobiology University of Southern California, Los Angeles

Touch is vital for many human and animal behaviors, but our understanding of it lags other senses. We have deployed a suite of techniques to dissect mechanisms of touch perception in the mouse, from the biophysics of whisker bending to optogenetic manipulation of specific cortical circuits. I will present our recent work exploring how circuits of primary somatosensory cortex process sensory and motor signals to create a neural representation of tactile features during whisker-based object exploration.

Towards a multi-scale quantification of the structure and function of the neurovascular interface

Lecture
Date:
Tuesday, January 17, 2017
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Dr. Pablo Blinder
|
Dept of Neurobiology, Faculty of Life Sciences, Tel Aviv University

Abstract: Proper brain function depends on the intricate interface between neurons, astrocytes and the nearby blood vessels that supply then with oxygen and nutrients. Coupling between neuronal activity and local vascular responses represent both a fundamental physiological process and also underpins the mechanism behind BOLD-imaging techniques. We aim to systematically map the structure-function organization of this interface and use this knowledge as morphological framework to interpret neurovascular dynamics. At the system level, we find a puzzling lack of spatial organization between neuronal units of the lemniscal pathway and the surrounding vasculature. I will share these findings and describe our current efforts to map the neuro-vascular microcircuitry. To understand whether neurons wire with some preference into the vasculature, we started to simulate the expected “random" statistics for this morphological interface. In addition, I will share preliminary data showing a differential neuronal response to surgically induced hypo- and hyper-perfusion conditions; suggest a potential modulation role of systemic pressure on neuronal activity.

Coding with Correlated Neurons

Lecture
Date:
Tuesday, January 3, 2017
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Dr. Rava da Silveira
|
École Normale Supérieure, Paris, France

Arguably, quantitative neuroscience was born when scientists started to correlate the activity of a neuron with sensory stimuli. But complex stimuli, such as natural ones, are encoded in the activity of entire populations of neurons. What is the grammar of this code? Specifically, how are the correlations among neurons and their physiological diversity involved in this code? In this talk, I will discuss analyses of the output of populations of identified and simultaneously recorded visual neurons. In these populations, and against the textbook picture of neural population coding, correlations in the spiking variability enhance the coding performance. This unexpected phenomenon relies upon a particular structure of the correlations observed in data and, surprisingly, yields a strong effect even in very small populations of neurons. I will, further, explain how the favorable structure of correlations can emerge from simple circuit features. Finally, if time allows, I will present more general theoretical extensions in which, with the use of simple models, one can illustrate the massive influence that correlations and physiological diversity can have on the precision and capacity of the neural code.

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.

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