All events, 2008

Plasticity in the circadian clock and social organization in bees

Lecture
Date:
Tuesday, May 6, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Prof. Guy Bloch
|
Hebrew University of Jerusalem

In honeybees (Apis mellifera) natural plasticity in circadian rhythms is associated with the division of labor that organizes their colonies. "Nurse" bees (typically < 2 weeks old) care for brood around-the-clock whereas bees older than 3 weeks of age typically forage for flowers with strong circadian rhythms. We found that nurses care for brood around-the-clock even under a light/dark illumination regime. Brain oscillations in the abundance of the putative clock genes Period and Cryptochrom-m were attenuated or totally suppressed in nurses as compared to foragers, irrespective of the illumination regime. However, nurses showed circadian rhythms in locomotor activity and molecular oscillations in brain clock gene expression shortly after transfer from the hive to constant laboratory conditions. The onset of their activity occurred at the subjective morning, suggesting that some clock components were entrained even while in the hive and active around-the-clock. These results suggest that the hive environment induces reorganization of the molecular clockwork. To test this hypothesis, we studied activity and brain clock gene expression in young bees that were confined to a broodless area on the honeycomb in a light/ dark illuminated observation hive. These bees experienced the hive environment and could interact with other bees, but not with the brood. By contrast to same-age nurses from these colonies, the confined bees showed molecular oscillations in clock gene expression and were more active during the day. These findings are consistent with the hypothesis that interactions with the brood modulate plasticity in the molecular clockwork of the honeybee. These findings together with our previous research, suggest the evolution of sociality shaped the bee clock in a way that facilitate integration of individuals into a complex society.

Rational therapeutic strategies for modifying Alzheimer's disease: Abeta oligomers as the validated target

Lecture
Date:
Monday, April 28, 2008
Hour: 11:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Prof. Colin Masters
|
A Laureate Professor in the University of Melbourne & Executive Director of Mental Health Research Institute of Victoria

Medication Development for Treating Addiction: A New Strategy Focusing on the Brain's Dopamine D3 Receptor

Lecture
Date:
Sunday, April 27, 2008
Hour: 10:30
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Dr. Eliot Gardner
|
Chief, Neuropsychopharmacology Section National Institute on Drug Abuse, NIH

Medication discovery and development for the treatment of addictive diseases has focused for many decades on so-called 'substitution' therapies such as methadone for opiate addiction and the nicotine patch or nicotine chewing gum for nicotine addiction. Recent developments in understanding the underlying neurobiology of addiction, craving, and relapse now augur to revolutionize such medication discovery and development. It has long been understood that the meso-accumbens dopamine circuitry of the ventral mesolimbic midbrain and forebrain plays a crucial role in the acutely euphoric 'high' or 'rush' or 'blast' produced by addictive drugs. More recently, it has come to be understood that this brain circuitry is also critically involved in mediating drug craving and relapse to drug-seeking behavior. The dopamine D3 receptor is a remarkable neurotransmitter receptor in the brain. It exists virtually only in those dopaminergic circuits known to mediate drug-induced reward, drug craving, and relapse to drug-seeking behavior. Moreover, blockade of the D3 receptor enhances dopaminergic tone in those circuits. If drug addiction is - to some degree &#8211; a 'reward deficiency' disease, as postulated by many workers in addiction medicine, enhancing dopaminergic tone in these circuits could be therapeutic. This lecture will focus on a lengthy series of experiments- using animal models of addiction - that suggest that highly-selective dopamine D3 receptor antagonists show remarkable therapeutic potential as anti-addiction, anti-craving, and anti-relapse medications."

Phenomenology of hypnosis

Lecture
Date:
Wednesday, April 16, 2008
Hour: 10:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Dr. Alexander Solomonovich
|
Hypnosis Unit, Wolfson Medical Center

Astrocytes Regulation of Information Processing

Lecture
Date:
Tuesday, April 1, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Prof. Eshel Ben-Jacob
|
Tel Aviv University

In the last decade, following many findings about Neuro-Glia interaction, the perception of glia has been reconsidered. This lecture addresses astrocyte regulation of synaptic information transfer. I will present a simple biophysical model for the coupling between synaptic transmission and the local calcium concentration on an astrocyte domain that envelopes the synapse. We found that the special interaction and feedback loop between the astrocyte and the synapse activity enables the astrocyte to modulate the information flow from presynaptic to postsynaptic cells in a manner dependent on previous activity at this and other nearby synapses. Thus, it can introduce temporal and spatial correlations in the information transfer in neural networks. I will show that astrocyte intracellular calcium dynamics in response to the synaptic information flow can encode information in amplitude modulations, frequency modulations and mixed modulations that, in turn, regulate the information transfer in later time. I will discuss the possibility that such regulation mechanisms might hint to the existence of new principles of information processing in neural networks yet to be deciphered. The models, analysis and results will be presented for multidisciplinary audience.

Neurobiology of Mood Disorders: A developmental perspective

Lecture
Date:
Tuesday, March 25, 2008
Hour: 10:00
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. John Mann
|
Columbia University & The New York State Psychiatric Institute

Abstract: Past neurobiological models of mood disorders have not considered etiology or a developmental perspective. Recently enough data regarding candidate genes and the impact of adverse early experience has been published that the beginnings of a plausible and heuristically useful hypothetical causal model can be proposed. This talk will integrate known effects of susceptibility genes and childhood adversity in explaining the psychopathology and biological phenotype of major depression including data from postmortem studies and in vivo brain imaging.

Contrasting tuning properties of cortical and spinal neurons reveal distinct coding strategies

Lecture
Date:
Tuesday, March 18, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Dr. Yifat Prut
|
Hebrew University Jerusalem

When executing volitional movements an externally defined target must be translated into internally represented muscle activation. We studied this process of extrinsic-to-intrinsic transformation by simultaneously recording activity from motor cortex and cervical spinal cord of primates. Preferred directions (PD) of motor cortical neurons were uniformly distributed while spinal PDs were biased in a manner consistent with enhanced representation of flexor muscles. Changes in PDs during hand rotation were used to assign an extrinsic or intrinsic coordinate frame to recorded neurons. During trial performance firing of motor cortical neurons gradually shifted from an extrinsic to an intrinsic representation of movement. In contrast, representation in the spinal cord was consistently intrinsic. Finally, at movement onset, connected corticospinal neurons expressed a transient alignment of directional tuning consistent with an increased cortical drive operating at this time. We suggest that motor cortical neurons contain a mixed representation of intrinsic and extrinsic parameters, whereas a consistent muscle-based command is obtained only at the spinal level via the termination pattern of corticospinal pathways or local segmental processing. Furthermore, spinal processing translates a phasic cortical command into a sustained muscle activation. (Joint work with Yuval Yanai, Nofya Adamit, Itay Asher, Ran Harel).

From c-Fos to extracellular matrix remodelling in synaptic plasticity, learning, memory and epilepsy

Lecture
Date:
Monday, March 10, 2008
Hour: 12:30
Location:
Wolfson Building for Biological Research
Prof. Leszek Kaczmarek
|
Nencki Institute, Warsaw, Poland

The last twenty years of intense research have provided convincing evidence for a role of regulation of gene expression in control of long-term neuronal plasticity, including learning and memory. Starting from our discovery&#8211;in late eighties&#8211;of c-fos activation in those phenomena, we have focused on correlating the expression of c-fos mRNA and c-Fos protein in various cognition-related brain structures with neuronal plasticity, learning and memory. The major conclusion from our studies, as well as those by the others, is that c-Fos and its functional form, AP-1 transcription factor, is the best correlate of learning processes, especially of a novelty of the behavioral information, whose processing constitutes the very foundation of the learning phenomenon. However, our understanding of exact biological function(s) of c-Fos/AP-1 still remains largely missing. Recently, an extracellular proteolytic system, composed of tissue inhibitor of matrix metalloproteinases, TIMP-1 and matrix metalloproteinase-9, MMP-9, has emerged as a major AP-1 target in hippocampal neurons responding to enhanced neuronal activity. Structural remodeling of the dendritic spines and synapses is essential for synaptic plasticity, underlying learning and memory. Matrix metalloproteinases are pivotal for tissue remodeling throughout the body, especially during development. Matrix metalloproteinase 9 (MMP-9) is an extracellularly operating enzyme that have recently been implicated in dendritic remodeling, synaptic plasticity, learning and memory (Szklarczyk et al., J. Neurosci., 2002; Nagy et al., J. Neurosci., 2006; Okulski et al., Biol. Psych., 2007). Furthermore, we have recently identified MMP-9 as a being produced, expressed and active at the synaptic contacts (Konopacki et al., Neuroscience, 2007; Michaluk et al., J. Biol. Chem., 2007; Wilczynski et al., J. Cell Biol. in press). Most recently, we have also found that MMP-9 plays a key pathogenic role in two animal models of temporal lobe epilepsy (TLE): kainate-evoked-epilepsy and pentylenetetrazole (PTZ) kindling-induced epilepsy. TLE is a devastating disease in which aberrant synaptic plasticity plays a major role Notably, we show that the sensitivity to PTZ-epileptogenesis is decreased in MMP-9 KO mice, but is increased in novel strain of transgenic rats, we have produced to overexpress MMP-9 selectively in neurons. Immunoelectron microscopy has revealed that MMP-9 associates with hippocampal dendritic spines bearing asymmetric (excitatory) synapses, where both the MMP-9 protein levels and enzymatic activity become strongly increased upon seizures. Further, we find that MMP-9-deficiency diminishes seizure-evoked pruning of dendritic spines and decreases aberrant synaptogenesis following mossy-fibers sprouting. The latter observation provides a possible mechanistic basis for the effect of MMP-9 on epileptogenesis. Our work suggests that a synaptic pool of MMP-9 is critical for the sequence of events that underlie the development of seizures in animal models of TLE.

Preattentive Processing of Sound Space

Lecture
Date:
Tuesday, March 4, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Dr. Leon Deouell
|
Hebrew University Jerusalem

Space has a pivotal role in perception, attention, and conscious awareness. In particular, space may link information obtained through different modalities such as vision and audition. However, the cortical basis of spatial processing in the auditory modality remains elusive. Especially, there are several open questions about the degree to which space is encoded for sounds which are outside the focus of attention. I will discuss recent fMRI and ERP studies investigating this issue. Human fMRI studies suggest that a part of the planum temporale (PT) is involved in auditory spatial processing, but it was recently argued that this region is active only when the task requires voluntary spatial localization. I will describe a series of fMRI experiments that challenge this notion. This will be corroborated with studies of the mismatch negativity (MMN) event related potential involving spatial change detection. Having shown fine preattentive spatial auditory tuning, I will address conditions under which this process can be nevertheless suppressed.

Where but not what: The fusion of reafferent and exafferent inputs to perceive the location of objects

Lecture
Date:
Sunday, February 17, 2008
Hour: 11:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. David Kleinfeld
|
UCSD

Sensory perception in natural environments involves the dual challenge to encode external stimuli and manage the influence of changes in body position that alter the sensory field. To examine mechanisms used to integrate sensory signals elicited by both external stimuli and motor activity, we use a mixture of psychophysics and electrophysiology to study rats trained to perform an active sensory task with a single vibrissa. We identify a nonlinear interaction between vibrissa touch and a motion-derived signal that dynamically labels each neuron with a preferred phase. The observed response enables the rodent to estimate object position in a head-centered reference frame. More generally, our result delineates a computation that is likely to occur in all active sensorimotor systems.

Pages

All events, 2008

Medication Development for Treating Addiction: A New Strategy Focusing on the Brain's Dopamine D3 Receptor

Lecture
Date:
Sunday, April 27, 2008
Hour: 10:30
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Dr. Eliot Gardner
|
Chief, Neuropsychopharmacology Section National Institute on Drug Abuse, NIH

Medication discovery and development for the treatment of addictive diseases has focused for many decades on so-called 'substitution' therapies such as methadone for opiate addiction and the nicotine patch or nicotine chewing gum for nicotine addiction. Recent developments in understanding the underlying neurobiology of addiction, craving, and relapse now augur to revolutionize such medication discovery and development. It has long been understood that the meso-accumbens dopamine circuitry of the ventral mesolimbic midbrain and forebrain plays a crucial role in the acutely euphoric 'high' or 'rush' or 'blast' produced by addictive drugs. More recently, it has come to be understood that this brain circuitry is also critically involved in mediating drug craving and relapse to drug-seeking behavior. The dopamine D3 receptor is a remarkable neurotransmitter receptor in the brain. It exists virtually only in those dopaminergic circuits known to mediate drug-induced reward, drug craving, and relapse to drug-seeking behavior. Moreover, blockade of the D3 receptor enhances dopaminergic tone in those circuits. If drug addiction is - to some degree &#8211; a 'reward deficiency' disease, as postulated by many workers in addiction medicine, enhancing dopaminergic tone in these circuits could be therapeutic. This lecture will focus on a lengthy series of experiments- using animal models of addiction - that suggest that highly-selective dopamine D3 receptor antagonists show remarkable therapeutic potential as anti-addiction, anti-craving, and anti-relapse medications."

Phenomenology of hypnosis

Lecture
Date:
Wednesday, April 16, 2008
Hour: 10:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Dr. Alexander Solomonovich
|
Hypnosis Unit, Wolfson Medical Center

Astrocytes Regulation of Information Processing

Lecture
Date:
Tuesday, April 1, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Prof. Eshel Ben-Jacob
|
Tel Aviv University

In the last decade, following many findings about Neuro-Glia interaction, the perception of glia has been reconsidered. This lecture addresses astrocyte regulation of synaptic information transfer. I will present a simple biophysical model for the coupling between synaptic transmission and the local calcium concentration on an astrocyte domain that envelopes the synapse. We found that the special interaction and feedback loop between the astrocyte and the synapse activity enables the astrocyte to modulate the information flow from presynaptic to postsynaptic cells in a manner dependent on previous activity at this and other nearby synapses. Thus, it can introduce temporal and spatial correlations in the information transfer in neural networks. I will show that astrocyte intracellular calcium dynamics in response to the synaptic information flow can encode information in amplitude modulations, frequency modulations and mixed modulations that, in turn, regulate the information transfer in later time. I will discuss the possibility that such regulation mechanisms might hint to the existence of new principles of information processing in neural networks yet to be deciphered. The models, analysis and results will be presented for multidisciplinary audience.

Neurobiology of Mood Disorders: A developmental perspective

Lecture
Date:
Tuesday, March 25, 2008
Hour: 10:00
Location:
Gerhard M.J. Schmidt Lecture Hall
Prof. John Mann
|
Columbia University & The New York State Psychiatric Institute

Abstract: Past neurobiological models of mood disorders have not considered etiology or a developmental perspective. Recently enough data regarding candidate genes and the impact of adverse early experience has been published that the beginnings of a plausible and heuristically useful hypothetical causal model can be proposed. This talk will integrate known effects of susceptibility genes and childhood adversity in explaining the psychopathology and biological phenotype of major depression including data from postmortem studies and in vivo brain imaging.

Contrasting tuning properties of cortical and spinal neurons reveal distinct coding strategies

Lecture
Date:
Tuesday, March 18, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Dr. Yifat Prut
|
Hebrew University Jerusalem

When executing volitional movements an externally defined target must be translated into internally represented muscle activation. We studied this process of extrinsic-to-intrinsic transformation by simultaneously recording activity from motor cortex and cervical spinal cord of primates. Preferred directions (PD) of motor cortical neurons were uniformly distributed while spinal PDs were biased in a manner consistent with enhanced representation of flexor muscles. Changes in PDs during hand rotation were used to assign an extrinsic or intrinsic coordinate frame to recorded neurons. During trial performance firing of motor cortical neurons gradually shifted from an extrinsic to an intrinsic representation of movement. In contrast, representation in the spinal cord was consistently intrinsic. Finally, at movement onset, connected corticospinal neurons expressed a transient alignment of directional tuning consistent with an increased cortical drive operating at this time. We suggest that motor cortical neurons contain a mixed representation of intrinsic and extrinsic parameters, whereas a consistent muscle-based command is obtained only at the spinal level via the termination pattern of corticospinal pathways or local segmental processing. Furthermore, spinal processing translates a phasic cortical command into a sustained muscle activation. (Joint work with Yuval Yanai, Nofya Adamit, Itay Asher, Ran Harel).

From c-Fos to extracellular matrix remodelling in synaptic plasticity, learning, memory and epilepsy

Lecture
Date:
Monday, March 10, 2008
Hour: 12:30
Location:
Wolfson Building for Biological Research
Prof. Leszek Kaczmarek
|
Nencki Institute, Warsaw, Poland

The last twenty years of intense research have provided convincing evidence for a role of regulation of gene expression in control of long-term neuronal plasticity, including learning and memory. Starting from our discovery&#8211;in late eighties&#8211;of c-fos activation in those phenomena, we have focused on correlating the expression of c-fos mRNA and c-Fos protein in various cognition-related brain structures with neuronal plasticity, learning and memory. The major conclusion from our studies, as well as those by the others, is that c-Fos and its functional form, AP-1 transcription factor, is the best correlate of learning processes, especially of a novelty of the behavioral information, whose processing constitutes the very foundation of the learning phenomenon. However, our understanding of exact biological function(s) of c-Fos/AP-1 still remains largely missing. Recently, an extracellular proteolytic system, composed of tissue inhibitor of matrix metalloproteinases, TIMP-1 and matrix metalloproteinase-9, MMP-9, has emerged as a major AP-1 target in hippocampal neurons responding to enhanced neuronal activity. Structural remodeling of the dendritic spines and synapses is essential for synaptic plasticity, underlying learning and memory. Matrix metalloproteinases are pivotal for tissue remodeling throughout the body, especially during development. Matrix metalloproteinase 9 (MMP-9) is an extracellularly operating enzyme that have recently been implicated in dendritic remodeling, synaptic plasticity, learning and memory (Szklarczyk et al., J. Neurosci., 2002; Nagy et al., J. Neurosci., 2006; Okulski et al., Biol. Psych., 2007). Furthermore, we have recently identified MMP-9 as a being produced, expressed and active at the synaptic contacts (Konopacki et al., Neuroscience, 2007; Michaluk et al., J. Biol. Chem., 2007; Wilczynski et al., J. Cell Biol. in press). Most recently, we have also found that MMP-9 plays a key pathogenic role in two animal models of temporal lobe epilepsy (TLE): kainate-evoked-epilepsy and pentylenetetrazole (PTZ) kindling-induced epilepsy. TLE is a devastating disease in which aberrant synaptic plasticity plays a major role Notably, we show that the sensitivity to PTZ-epileptogenesis is decreased in MMP-9 KO mice, but is increased in novel strain of transgenic rats, we have produced to overexpress MMP-9 selectively in neurons. Immunoelectron microscopy has revealed that MMP-9 associates with hippocampal dendritic spines bearing asymmetric (excitatory) synapses, where both the MMP-9 protein levels and enzymatic activity become strongly increased upon seizures. Further, we find that MMP-9-deficiency diminishes seizure-evoked pruning of dendritic spines and decreases aberrant synaptogenesis following mossy-fibers sprouting. The latter observation provides a possible mechanistic basis for the effect of MMP-9 on epileptogenesis. Our work suggests that a synaptic pool of MMP-9 is critical for the sequence of events that underlie the development of seizures in animal models of TLE.

Preattentive Processing of Sound Space

Lecture
Date:
Tuesday, March 4, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Dr. Leon Deouell
|
Hebrew University Jerusalem

Space has a pivotal role in perception, attention, and conscious awareness. In particular, space may link information obtained through different modalities such as vision and audition. However, the cortical basis of spatial processing in the auditory modality remains elusive. Especially, there are several open questions about the degree to which space is encoded for sounds which are outside the focus of attention. I will discuss recent fMRI and ERP studies investigating this issue. Human fMRI studies suggest that a part of the planum temporale (PT) is involved in auditory spatial processing, but it was recently argued that this region is active only when the task requires voluntary spatial localization. I will describe a series of fMRI experiments that challenge this notion. This will be corroborated with studies of the mismatch negativity (MMN) event related potential involving spatial change detection. Having shown fine preattentive spatial auditory tuning, I will address conditions under which this process can be nevertheless suppressed.

Where but not what: The fusion of reafferent and exafferent inputs to perceive the location of objects

Lecture
Date:
Sunday, February 17, 2008
Hour: 11:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. David Kleinfeld
|
UCSD

Sensory perception in natural environments involves the dual challenge to encode external stimuli and manage the influence of changes in body position that alter the sensory field. To examine mechanisms used to integrate sensory signals elicited by both external stimuli and motor activity, we use a mixture of psychophysics and electrophysiology to study rats trained to perform an active sensory task with a single vibrissa. We identify a nonlinear interaction between vibrissa touch and a motion-derived signal that dynamically labels each neuron with a preferred phase. The observed response enables the rodent to estimate object position in a head-centered reference frame. More generally, our result delineates a computation that is likely to occur in all active sensorimotor systems.

A hierarchy of temporal receptive windows in human cortex

Lecture
Date:
Tuesday, February 12, 2008
Hour: 12:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Dr. Uri Hasson
|
New York University

Real-world events unfold at different time scales, and therefore cognitive and neuronal processes must likewise occur at different time scales. In the talk I will present a novel procedure that identifies brain regions responsive to the preceding sequence of events (past time) over different time scales. The fMRI activity was measured while observers viewed silent films presented forward, backward, or piecewise-scrambled in time. The results demonstrate that responses in different brain areas are affected by information that has been accumulated over different time scales, with a hierarchy of temporal receptive windows spanning from short (~4 s) to intermediate (~12 s) and long (~ 36 s). Thus, although we adopted an open-ended experimental protocol (free viewing of complex stimuli), we found that parametric manipulation of the temporal structure of a complex movie sequence produced lawful changes in cortical activity across different brain regions. In addition to the reliable cortical response patterns, I will also show that films exerted considerable control over the subjects' behavior (i.e., eye movements or galvanic skin responses). Finally, I will present few applications of this method for studying the neuronal correlates of complex human behaviors under more natural settings.

Information-theoretic analysis of neural data: why do it, why it is challenging, and what can be learned

Lecture
Date:
Tuesday, February 5, 2008
Hour: 12:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Jonathan Victor
|
Cornell University

Entropy and information are quantities of interest to neuroscientists, because of their mathematical properties and because they place limits on the performance of a neural system. However, estimating these quantities from neural spike trains is much more challenging than estimating other statistics, such as mean and variance. The central difficulty in estimating information is tightly linked to the properties of information that make it a desirable quantity to estimate. To surmount this fundamental difficulty, most approaches to estimation of information rely (perhaps implicitly) on a model for how spike trains are related. But the nature of these model assumptions vary widely. As a result, information estimates are useful not only in situations in which several approaches provide mutually consistent results, but also in situations in which they differ. These ideas are illustrated with examples from the visual and gustatory systems.

Pages

All events, 2008

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All events, 2008

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