All events, All years

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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Trying to make sense of the cerebellum: models and experiments

Lecture
Date:
Tuesday, December 4, 2007
Hour: 12:15
Location:
Jacob Ziskind Building
Dr. Opher Donchin
|
Department of Biomedical Engineering Ben Gurion University, Beer Sheva

In this talk I will describe a recent controversy that has arisen regarding the intrinsic properties of Purkinje cells and explain the importance of this controversy to our understanding of Cerebellar function. In brief, it has been shown that Purkinje cell membrane potential is bistable, but there remains significant disagreement about whether this bistability has a functional role. In our lab, we addressed the controversy by recording from Purkinje cells in an awake animal and testing to see whether bistability that had been observed in vitro and in anaesthetized animals could also be seen in a behaving animal. Our findings will not settle the controversy, nor settle the question of the Cerebellum's functional role, but they will significantly shift the terms of the debate. We found that all of the predictions we tested confirmed the potential for a functional role for Purkinje cell bistability. This will force a serious re-evaluation of our understanding of Cerebellar circuitry.

The accessory olfactory (vomeronasal) system: a sensory adapted for social interactions

Lecture
Date:
Tuesday, November 20, 2007
Hour: 12:15
Location:
Jacob Ziskind Building
Dr. Shlomo Wagner
|
Dept of Biology and Dept of Neurobiology and Ethology, Haifa University

Many mammals rely on pheromones to mediate social interactions. Traditionally pheromones were thought to be detected by the accessory olfactory (vomeronasal) system, but recent studies indicated a central role for the main olfactory system in this function. Thus, unraveling the functional difference between these two chemosensory systems is essential for understanding pheromone-mediated social interactions. In this study we show that mitral cells of the accessory olfactory bulb respond to sensory input in a bimodal manner: a transient response is elicited by low level stimulation, whereas strong stimuli evoke sustained firing that lasts for 10-30 s. This is in sharp contrast to the unimodal response of main olfactory bulb mitral cells. We further show that this difference is dictated by distinct membrane properties of the two neuronal populations. We hypothesize that, via its sustained activity, the accessory olfactory system induces a new sensory state in the animal, reflecting its social context.

Clarifying the functional neuro-anatomy of face processing by combining lesion studies and neuroimaging

Lecture
Date:
Tuesday, November 13, 2007
Hour: 14:30
Location:
Nella and Leon Benoziyo Building for Brain Research
Prof. Bruno Rossion
|
University of Louvain, Belgium

Understanding the functional neuro-anatomy of face processing in the human brain is a long-standing goal of Cognitive Neuroscience. Up to the early 90&#8217;s, the most important source of knowledge was from lesion studies, i.e. making correlations between the localization of lesions in groups of brain-damaged patients and their face recognition impairments. The influence of the cognitive approach in Neuropsychology, with an emphasis on single-case functional investigations, as well as the advent of neuroimaging studies in the healthy brain, have considerably reduced the importance of lesion studies in clarifying the neuro-anatomical aspects of face processing. In this talk, my goal will be to illustrate how neuroimaging investigations of single-cases of acquired prosopagnosic patients can still greatly increase our knowledge in this field. Neuroimaging studies of the normal brain have shown that the middle fusiform gyrus (&#8216;FFA&#8217;) and the inferior occipital gyrus (&#8216;OFA&#8217;) are activated by both detection and identification of faces. Among other observations, our studies of the patient PS, a case of prosopagnosia with normal object recognition, show that the right &#8216;FFA&#8217; can be recruited to detect faces independently of the &#8216;OFA&#8217; of the same hemisphere (Rossion et al., 2003). However, fMRI-adaptation investigations suggest that both areas are necessary to perform individual discrimination of faces (Schiltz et al., 2006). Recent observations also show that the the same brain area, here the right &#8216;FFA&#8217;, may be impaired at individual face discrimination while performing normal individual object discrimination. This suggests that clusters of neurons coding specifically for different categories in this area (Grill-Spector et al., 2006) can be functionnally independent. Finally, when structurally intact, non-face preferring areas such as the ventral part of the lateral occipital complex (vLOC) may subtend residual individual discrimination of faces following prosopagnosia. Altogether, these studies show that faces are processed through multiple pathways in the human brain, with a subset of these areas responding preferentially to faces being critical for efficient face recognition.

Compulsive Rats and Compulsive Humans

Lecture
Date:
Tuesday, November 13, 2007
Hour: 12:15
Location:
Jacob Ziskind Building
Dr. Daphna Joel
|
Dept of Psychology, Tel Aviv University

Obsessive-compulsive disorder (OCD) is a psychiatric disorder affecting 1-3% of the population. Although several brain regions have been implicated in the pathophysiology of OCD, including the basal ganglia-thalamo-cortical circuits and the dopaminergic and serotonergic systems, the ways in which these neural systems interact to produce obsessions and compulsions in patients is currently unknown. Moreover, although to date, there are effective pharmacological and behavioral treatments to OCD, many patients do not respond to these treatments. For obvious reasons, the understanding and treatment of diseases such as OCD, must rely heavily on appropriate animal models that closely mimic their behavioral and if possible their neural manifestations. We have recently developed a new rat model of OCD, in which &#8216;compulsive&#8217; lever-pressing is induced by the attenuation of an external feedback of this behavior. Compulsive lever-pressing is abolished by selective serotonin reuptake inhibitors, but not by anxiolytic antipsychotic, and non-serotonergic antidepressant drugs, in accordance with the differential efficacy of these drugs in alleviating obsessions and compulsions in OCD patients. Compulsive lever-pressing is also sensitive to manipulations of the orbitofrontal cortex and of the dopaminergic and serotonergic systems, in line with different lines of evidence implicating these systems in the pathophysiology of OCD. The model is used to screen new pharmacological agents with anti-compulsive activity; to map brain regions in which high frequency stimulation exerts an anti-compulsive effect; to test the autoimmune hypothesis of OCD; to assess the role of genetic vulnerability in OCD; to unravel the role of female gonadal sex hormones in compulsive behavior; and to uncover the neural mechanisms of OCD

Molecular Mechanisms for the Initiation and Maintenance of Long Term Memory Storage

Lecture
Date:
Tuesday, November 6, 2007
Hour: 15:00
Location:
Dolfi and Lola Ebner Auditorium
Prof. Eric Kandel
|
Prof., Columbia University, NY Sr Investigator, Howard Hughes Medical Institute

Alzheimers disease amyloid plaques: Tombs or time bombs? Lipids induce release of neurotoxic oligomers from inert amyloid fibrils

Lecture
Date:
Tuesday, October 30, 2007
Hour: 12:15
Location:
Jacob Ziskind Building
Dr. Inna Kuperstein
|
Center of Human Genetics, Flanders Institute & KU, Leuven, Belgium

Alzheimer's disease (AD) is associated with the aggregation of Amyloid-beta peptide (A&#946;). It is more and more believed that neurotoxicity is caused during the A&#946; aggregation process, by soluble A&#946; oligomers species, and not by the A&#946; fibrils themselves that considered as inert end-products of the aggregation process. Nevertheless, stability of A&#946; fibrils might be overestimated. We found that inert A&#946; fibrils can be reversed to toxic oligomers in the presence of synthetic phospholipids and lipid rafts components as gangliosids, sphingomyelin and cholesterol. Interestingly, the equilibrium is not shifted towards monomeric A&#946; but rather towards soluble amyloid oligomers (backward oligomers). Biochemical and biophysical analysis reveals that backward oligomers are very similar to the oligomers found during the classical aggregation process of monomeric A&#946; (forward oligomers). Backward oligomers cause synaptic markers loss and immediate neurotoxicity to primary neurons followed by apoptotic cell death. In addition, mice brain icv. injection of backward amyloid oligomers causes Tau phosphorylation, Caspase 3 activation and memory impairment in mouse similarly to forward oligomers. Finally, we observe that release of toxic oligomers and subsequent neurotoxicity may be caused by other disease-associated amyloid peptides as TAU, Prion 1 and synthetic amyloidogenic peptide in the presence of lipids. We propose that lipid-induced fibrils disassembly and release of soluble oligomers is a common generic mechanism of amyloids. An important implication of our work is that amyloid plaques are not inert and should be considered as potential large reservoirs of neurotoxic oligomers that can rapidly be mobilized by lipids. Although lipid metabolism has been implicated in neurodegenerative diseases the precise involvement of lipids in basic toxicity mechanisms in AD is a major question. Our data could help to understand this A&#946; and lipid relationship in more detail.

Understanding Exploratory Behavior

Lecture
Date:
Tuesday, October 23, 2007
Hour: 12:15
Location:
Jacob Ziskind Building
Prof. Ilan Golani
|
Dept of Zoology, Tel Aviv University

Unlike the situation in neurophysiology, where the relevant variables are mostly known, it is not clear what is to be measured in the study of behavior; what is a reliable datum? What are the elementary patterns? To highlight the building blocks of movement and their organization we use 4 tools: (i) we study gradients: along the body dimension, in space and in time (in moment-to-moment behavior, ontogeny, and recovery). Gradients provide natural origins of axes for measurement, reveal how building blocks are gradually added on top of each other to form the animal's full repertoire, and unite seemingly disparate behaviors into continua. (ii) We systematically change coordinate systems, to find the ones highlighting invariant features. We use multiple kinematic variables to describe the behavior. They may or may not cluster into discrete patterns. (iii) We study behavior on more than one scale. For example, along the body dimension we use 2 scales that of the path, and that of multi-limb coordination. Finally, (iv) we segment movement using intrinsic geometrical and statistical properties. By using combinations and conjunctions of the elementary building blocks we work our way up from low level to cognition- and motivation-related constructs. In my talk I will describe how these tools are implemented in a bottom-up study of mouse (Mus musculus) and fly (Drosophila melanogaster) exploratory behavior.

Linear and non-linear fluorescence imaging of neuronal activity

Lecture
Date:
Wednesday, September 19, 2007
Hour: 12:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Dr. Jonathan Fisher
|
Howard Hughes Medical Institute, The Rockefeller University, New York

Ca2+-Activated Currents in Mouse Gonadotrophs

Lecture
Date:
Thursday, September 6, 2007
Hour: 10:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Dr. Dennis W. Waring
|
Division of Endocrinology, Dept of Medicine, University of California, CA

Playing with sounds: How echolocating bats solve different approach tasks

Lecture
Date:
Wednesday, August 15, 2007
Hour: 12:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Dr. Mariana Melcon
|
Animal Physiology Section, Tubingen University, Germany

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