All events, All years

Role of dopamine systems in addiction

Lecture
Date:
Wednesday, November 26, 2008
Hour: 12:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Prof. Marco Diana
|
Laboratory of Cognitive Neuroscience Dept of Drug Sciences, University of Sassari, Italy

Dopamine neurons of the VTA, that project to the Nucleus Accumbens, have been involved in the initial rewarding properties of addicting compounds and, more appropriately, in the long-lasting changes observed after chronic drug administration and subsequent withdrawal. Indeed, alcohol, opiates cannabinoids and other substances provoke, upon withdrawal, a drastic and marked reduction of dopaminergic tone. In addition, aversive, non drug-related stimuli also reduce dopaminergic physiological tone. Furthermore, recent human studies reported an attenuated response to methylphenidate in alcoholic subjects and a lower (than controls) dopaminergic tone. These changes are paralleled by a lower number of D2 receptors and suggest a general “impoverishment” of dopamine transmission in the addicted brain. Accordingly, a dopamine deficit correlated with alcohol craving, which was associated with a high relapse risk. Similar results were reported for nicotine withdrawn rats. This hypodopaminergic state could be the target of therapies aimed at restoring the deficient dopamine transmission observed after chronic drug administration in preclinical and clinical investigations.

Interaction between the amygdala and the prefrontal cortex in emotional memory

Lecture
Date:
Tuesday, November 25, 2008
Hour: 12:30
Location:
Jacob Ziskind Building
Dr. Mouna Maroun
|
Department of Neurobiology and Ethology University of Haifa

The amygdala and the medial prefrontal cortex interact to guide emotional behavior. Alterations in the balance between these two structures can lead to persistent fear associations and to the development of anxiety disorders. In this talk I will present work from my laboratory studying the interaction between these two structures in normal conditions and when exposed to a fearful or stressful experience. We have recently found that fear and extinction learning induce differential changes in these two structures that could hint on the mechanisms by which these structures encode memories of fear and safety.

ON THE RELATIONSHIP BETWEEN MOTOR AND PERCEPTUAL BEHAVIOR –

Lecture
Date:
Wednesday, November 12, 2008
Hour: 12:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Dr. Andrei Gorea
|
Laboratoire Psychologie de la Perception CNRS & Paris Descartes University

Starting with Goodale & Milner's (1992) neuropsychological observations, a large number of neuropsychological and psychophysical studies has documented a putative dissociation between perception and action. However, a closer inspection of this literature reveals a number of methodological and conceptual shortcomings. I shall present a series of experiments making use of a variety of psychophysical techniques designed to gauge the relationship between Response Times as well Saccade Perturbations and observers' Perceptual States as assessed for not-masked and masked (metacontrast) stimuli via Yes/No, Temporal Order Judgments and Anticipation Response Times paradigms. All these studies reveal a strong action-perceptual state correlation indicating that motor and perceptual responses are based on a unique internal response. A one-path-two-decisions stochastic race model drawing on standard Signal Detection Theory provides a fair account of some of these data, hence overruling the necessity of a two-paths model of visual processing.

New insights into the hallmarks of obsessive-compulsive disorder (OCD): The prevalence of incompleteness and pessimal behavior

Lecture
Date:
Tuesday, November 11, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Prof. David Eilam
|
Dept of Zoology, Tel Aviv University

Performance of OCD patients was compared with that of matched normal individuals who were asked to perform the same task that the patients ascribed to their performance. Sequences of consecutive functional acts were long in controls and short in OCD, whereas sequences of non-functional acts were short in controls and long in OCD. Non-functional acts accumulated as a "tail" after the natural termination of the task, supporting the notion of incompleteness as an underling mechanism in OCD. It is suggested that the identified properties are consistent with a recent hypothesis that the individual's attention in OCD shifts from a normal focus on structured actions to a pathological attraction onto the processing of basic acts, a shift that invariably overtaxes memory. Such characteristics and mechanisms of compulsive rituals may prove useful in objective assessment of psychiatric disorders, behavioral therapy, and OCD nosology.

An embedded subnetwork of highly active neurons in the cortex

Lecture
Date:
Wednesday, November 5, 2008
Hour: 14:30
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Dr. Lina Yassin
|
Dept of Biological Sciences & Center for the Neural Basis of Cognition Carnegie Mellon University, Pittsburgh, PA

In vivo and in vitro, spontaneous and evoked neuronal activity are sparsely distributed across neocortical networks, where only a small subset of cells show firing rates greater than 1 Hz. Understanding the stability, network connectivity, and functional properties of this active subpopulation has been hampered by an inability to identify and characterize these neurons in vitro. Here we use expression of a fosGFP transgene to identify and characterize the properties of cells with a recent history of elevated activity. Neurons that had induced fosGFP expression in vivo maintained elevated firing rates in vitro over the course of many hours. Paired-cell recordings indicated that fosGFP+ neurons have a greater likelihood of being connected to each other, both directly and indirectly. These findings indicate that highly active neuronal ensembles are maintained over long time periods and suggest that specific, identifiable groups of neurons may dominate the way information is represented in the neocortex.

Voltage-Gated Sodium Channels in Neocortical Pyramidal Neurons:

Lecture
Date:
Tuesday, November 4, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Prof. Mike Gutnick
|
Koret School of Veterinary Medicine The Hebrew University of Jerusalem, Rehovot

CARBOXYPEPTIDASE E: ROLE IN PEPTIDERGIC VESICLE TRANSPORT, NEUROPROTECTION AND CANCER

Lecture
Date:
Tuesday, October 28, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Dr. Y. Peng Loh
|
Section on Cellular Neurobiology, Program on Developmental Neuroscience, NICHD, NIH, Bethesda

Carboxypeptidase E (CPE) is a prohormone processing enzyme that cleaves C-terminal basic residues from peptide hormone intermediates to yield active hormones, within secretory granules of neuroendocrine cells. A transmembrane form of the enzyme has been shown to be a sorting receptor that sorts prohormones and BDNF at the trans Golgi network and targets them to the regulated secretory pathway. Recently, live cell imaging studies have demonstrated that transport of peptidergic/BDNF secretory vesicles to the release site is dependent upon CPE. The cytoplasmic tail of CPE on the vesicles binds to microtubule motors, KIF1A/KIF3A and dynein via dynactin to effect transport of prohormone/BDNF vesicles in a bidirectional manner from the soma to the process terminals and return. In addition, CPE has been found to play a neuroprotective role in adult brain. In CPE-knockout (KO) mice, degeneration of pyramidal neurons was observed in the hippocampal CA3 region of animals equal or greater than 4 weeks of age, whereas the hippocampus was intact at 3 weeks and younger. Calbindin staining indicated early termination of the mossy fibers before reaching the CA1 region, and a lack of staining of the pyramidal neurons and apical dendritic arborizations in the CA1 region of CPE-KO mice. Ex vivo studies showed that cultured hippocampal neurons transfected with an enzymatically inactive form of CPE were protected against H2O2 oxidative-stress-induced cell death but not in non-transfected or LacZ transfected neurons. Thus CPE has an anti-apoptotic role in the maintenance of survival of adult hippocampal CA3 neurons, although the mechanism of action is unknown. In hepatocellular carcinoma (HCC) cells, overexpression of CPE resulted in enhanced proliferation and migration. SiRNA knockdown of CPE expression in highly metastatic HCC cells inhibited their growth and metastasis in nude mice. These results indicate that CPE is a new mediator of tumor growth and metastasis. Thus CPE is a multi-functional protein which actions include both enzymatic and non-enzymatic to mediate various physiological functions.

Population imaging in vivo: from the awake to the anesthetized

Lecture
Date:
Tuesday, October 7, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Prof. Jason Kerr
|
Max Planck Institute, Tubingen, Germany

It is unclear how the complex spatiotemporal organization of ongoing cortical neuronal activity recorded in anesthetized animals relates to the awake animal. We therefore used two-photon population calcium imaging in awake and subsequently anesthetized rats to follow action potential firing in populations of neurons across brain states, and examined how single neurons contributed to population activity. Firing rates and spike bursting in awake rats were higher, and pair-wise correlations were lower, compared with anesthetized rats. Anesthesia modulated population-wide synchronization and the relationship between firing rate and correlation. Overall, brain activity during wakefulness cannot be inferred using anesthesia.

Decoding conscious and unconscious mental states from brain activity in humans

Lecture
Date:
Tuesday, September 23, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Prof. Dr. John-Dylan Haynes
|
Bernstein Center for Computational Neuroscience, Charité Berlin & Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany

Recent advances in human neuroimaging have shown that it is possible to accurately read out a person's conscious experience based only on non-invasive fMRI measurements of their brain activity. This "brain reading" is possible because each thought is associated with a unique pattern of brain activity that can serve as a "fingerprint" of this thought in the brain. By training a computer to recognize these fMRI "thought patterns" it is possible to read out what someone is currently thinking with high accuracy. Here several studies will be presented that also directly address the relationship between neural encoding of information (as measured with fMRI) and its availability for awareness. These studies include comparisons of neural and perceptual information, unconscious information processing, decoding of time courses of perception, as well as decoding of high-level mental states. This will show that it is possible to read out a person's concealed intentions and even to predict how someone is going to decide a few seconds later. Finally, the talk will discuss fundamental challenges and limitations of the field, along with the ethical question if such methods might one day be a danger to our mental privacy.

Benoziyo Center for Neurological Diseases - Fourth Annual Symposium

Conference
Date:
Sunday, September 21, 2008
Hour:
Location:

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The Embryonic Neural Crest, from Specification to the Generation of Cellular Movement

Lecture
Date:
Tuesday, May 13, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Prof. Chaya Kalcheim
|
Hebrew University of Jerusalem

The neural crest (NC) is a transient group of progenitors present in vertebrate embryos. Its component cells yield an extensive variety of derivatives such as melanocytes, neurons of many kinds, glial , ectomesenchymal and endocrine cells. Initially, presumptive NC cells are an integral part of the neuroepithelium. Subsequently, a time and axial level-specific conversion from an epithelial to a mesenchymal (EMT) state causes the cells to become motile and engage in migration. Mesenchymal NC cells then advance through stereotyped pathways, reach their homing sites and then differentiate. The molecular network underlying NC delamination and the generation of cell movement remained incompletely understood. We found that a balance between BMP and its inhibitor noggin underlies the emigration of NC independently of earlier cell specification. BMP induces delamination by triggering Wnt1 transcription. Canonical Wnt signaling promotes G1/S transition which is a necessary step for delamination of trunk NC. Successful delamination also requires the activity of effector genes that act on re-organisation of the actin cytoskeleton and alterations in adhesive properties. In this context, we found that both N-cadherin and RhoGTPase signaling play a negative modulatory role on the process. During the course of our work, we observed that in the trunk, NC cells continuously delaminate from the NT for over two days, raising the fundamental question of the source and mechanisms accounting for the production of successive waves of NC progenitors. We found that the first NC to delaminate reside in the dorsal midline of the NT and generate sympathetic ganglia, and successive waves translocate ventrodorsally in the NT to replenish the dorsal midline and then delaminate. Hence, the dorsal midline is a dynamic region traversed sequentially by progenitors that colonize NC derivatives in a ventral to dorsal order (chromaffin cells, sympathetic ganglia, then Schwann cells, DRG and finally melanocytes). Based on our data invoking a dynamic behavior of premigratory NC cells, we hypothesize the existence of a spatiotemporal fate map of derivatives present already within the NT and defined by a specific molecular code.

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.

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