All events, All years

Rule-Rationality versus Act-Rationality

Lecture
Date:
Tuesday, December 30, 2008
Hour: 12:30
Location:
Jacob Ziskind Building
Prof. Yisrael Aumann
|
Nobel Prize Laureate in Economics, 2005 The Center for the Study of Rationality Hebrew University, Jerusalem

People's actions often deviate from rationality, i.e., self-interested behavior. We propose a paradigm called rule-rationality, according to which people do not maximize utility in each of their acts, but rather follow rules or modes of behavior that usually---but not always---maximize utility. Specifically, rather than choosing an act that maximizes utility among all possible acts in a given situation, people adopt rules that maximize average utility among all applicable rules, when the same rule is applied to many apparently similar situations. The distinction is analogous to that between Bentham's "act-utilitarianism'' and the "rule-utilitarianism'' of Mill, Harsanyi, and others. The genesis of such behavior is examined, and examples are given. The paradigm may provide a synthesis between rationalistic neo-classical economic theory and behavioral economics.

Nonlinearity, memory, and phase transitions in learning

Lecture
Date:
Thursday, December 25, 2008
Hour: 12:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Dr. Ilya Nemenman
|
Computer, Computation and Statistical Sciences Division & Center for Nonlinear Studies Los Alamos National Laboratory

Abstracting from physiological details, I will present a theory that suggests an explanation behind critical periods in learning as a natural consequence of learning dynamics under a small and realistic set of assumptions. Surprisingly, the same theory offers an explanation for other animal learning phenomena, such as the tendency to reverse to the status quo following a transient learning experience. Additionally, the theory suggests simple experiments that can be used to prove or refute it. If the time permits, as a commercial for future results, I will finish the talk with a brief overview of recent attempts at LANL for petascale simulations of the mammalian visual cortex.

Salience-based selection: How does the brain ignore saliency?

Lecture
Date:
Tuesday, December 23, 2008
Hour: 12:30
Location:
Jacob Ziskind Building
Dr. Carmel Mevorach
|
Behavioral Brain Sciences Centre University of Birmingham UK

At any particular time the brain is bombarded with an almost infinite amount of visual information. Efficient behaviour, then, relies on a process of attentional selection which is required to filter out irrelevant stimuli and to prioritize the processing of relevant events. Importantly, this attentional prioritisation process needs to be flexible in order to be responsive to changes in behavioural relevance. Thus, bottom-up cues for attention must be modulated by top-down information, reflecting the goals of behaviour. In recent years, considerable neurobiological evidence has accumulated indicating that flexible visual selection is controlled by a fronto-parietal network within the brain. In particular, the posterior parietal cortex (PPC) has been implicated both when spatial selection is required and when selection is non-spatial. In a series of recent studies we have used converging operations to demonstrate a link between the PPC and a form of non-spatial selection – selecting on the basis of the relative salience of the stimuli. Using variants of the classic Global/Local task we orthogonally manipulated the level of shape that participants responded to and the salience of that information. Using experimental techniques such as neuropsychological studies, Trans-cranial Stimulation (TMS) and functional imaging (fMRI) we show that the PPC is sensitive to the relative saliency of the information so that selection can be based on whether the target or the distractor are more salient. Most importantly, we provide evidence for distinct roles played by the right and left PPC in selection and suppression of saliency, respectively. The data may also suggest how such complementary forms of selection are implemented in the brain.

Representation of the visual field in object-selective cortex

Lecture
Date:
Wednesday, December 17, 2008
Hour: 15:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Dr. Rory Sayres
|
Dept of Psychology, Stanford University

Functional MRI (fMRI) studies have defined a series of visual processing regions in the human cortex, which are believed to enable visual recognition behaviors through a hierarchy of processing stages. At the higher stages in this hierarchy lie regions which preferentially respond to images of intact objects compared to other visual stimuli, a set of regions collectively termed object-selective cortex. Within object-selective cortex exist category-selective regions, which prefer particular categories of images over others (e.g., faces, body parts, houses or scenes). Initially these regions were considered non-retinotopic, but increasing evidence indicates substantial retinal position selectivity, and in some cases retinotopy, in these regions. What is the representation of the visual field in object-selective regions? Are separate object- and category-selective regions part of a single map or embedded within a set of distinct visual field maps? We scanned seven subjects on separate experiments to localize object/category-selective regions, and measure visual field maps (GE 3T scanner). For retinotopic experiments, subjects viewed moving bar stimuli containing different stimuli, including slowly drifting checkerboards and frontal face images. The bars extended out to around 14° eccentricity from the fovea, and had a width of ~2.6°. We employed a recently-developed method for estimating population receptive fields (pRFs) using fMRI (Dumoulin and Wandell, Neuroimage, 2008), which estimates pRF center and size for each cortical location. Face-containing bars produced substantially larger responses than checkerboards along the fusiform gyrus, improving our ability to measure visual field maps in these regions. Eccentricity maps revealed two foveal representations, which may correspond to visual field map clusters previously identified as VO and VT (Wandell et al., Neuro-opth. Jpn., 2006). These foveas are within or adjacent to fusiform face-selective regions, and separated by smoothly-varying extra-foveal maps which are less face-selective. For several subjects, pRF sizes systematically increased with eccentricity in face-selective regions. The distribution of pRF sizes were substantially larger than in earlier visual cortex, but comparable to recent measurements made in lateral occipital cortex. We find two spatially separate face-selective regions along the fusiform gyrus, with comparable visual field coverage, separated by a representation of intermediate eccentricities. This indicates these two regions are likely to fall within different visual field maps. Current work addresses possible effects of low-level visual features (e.g. spatial frequency) and stimulus visibility in driving the observed face-selective retinotopic responses. I will also present some preliminary data from retinotopic mapping with house-containing bars, and an examination of retinotopic organization in house- or scene-selective cortical regions.

Active sensing: from natural stimulus statistics to auditory object classification in echolocating bats

Lecture
Date:
Tuesday, December 16, 2008
Hour: 12:30
Location:
Jacob Ziskind Building
Yossi Yovel
|
(Post-doc Ulanovsky Group) Department of Neurobiology, WIS

Echolocating bats perceive their surroundings acoustically. They continuously emit sonar signals and analyze the returning echoes, which enables them to orient in space and acquire food in complete darkness. Natural echoes along with other natural sounds compose a major part of the bat's sensory world, and have likely played a key evolutionary role in shaping the design of the bat's echolocation system and the auditory computations in the bat brain. However, the statistics of natural complex echoes, as well as how bats utilize them, are poorly understood – especially in the context of sonar-based object classification. The goal of this work was to elucidate the natural acoustical stimuli in the bat's world. I will present data on the statistical properties of complex echoes from various classes of plants and will compare them to what is known about natural images. In addition I will use a machine learning approach to discuss ways that bats may use to classify these stimuli. Finally, I will also describe behavioral experiments that aimed to understand the strategy used by bats to classify natural stimuli.

Optogenetics: Application to Neuroscience and Neuropsychiatry

Lecture
Date:
Monday, December 15, 2008
Hour: 11:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Karl Deisseroth
|
Depts of Bioengineering & Psychiatry, Stanford University

Optogenetics, synthesizing microbial opsins and solid-state optics, has achieved the goal of millisecond-precision bidirectional control of defined cell types in freely behaving mammals, but has not yet been widely applied to neuroscience and neuropsychiatry experimental challenges. First, relevant to important basic science questions, we have now successfully developed methods to target and control several classes of modulatory neurons in behaving mammals and intact neural tissue, and we are probing and quantifying measures of altered circuit performance under optogenetic control of defined circuit elements to address longstanding questions about neural circuit dynamics. Second, relevant to neuropsychiatric disease questions, we have used this approach for depth targeting of hypothalamic cells (in this case, the hypocretin/orexin cells in the lateral hypothalamus), establishing for the first time a causal relationship between frequency-dependent activity of genetically defined neurons important in clinical neuropsychiatric disease and a complex orchestrated mammalian behavior. We also are now applying fast optical control and optical imaging to animal models of depression, Parkinson’s Disease, and altered social behavior relevant to autism. Insights into both normal circuit function and disease mechanisms are beginning to emerge from this multidisciplinary technological approach. Prof. Deisseroth is hosted by the students of the Department of Neurobiology, as a part of the departmental students-invited visiting scientist program.

Optogenetics:Technology Development

Lecture
Date:
Sunday, December 14, 2008
Hour: 14:30
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Karl Deisseroth
|
Depts of Bioengineering& Psychiatry, Stanford University

In 1979, Francis Crick delineated the major challenges facing neuroscience and called for a technology by which all neurons of just one type could be controlled, “leaving the others more or less unaltered”. A new set of technologies now called optogenetics, synthesizing microbial opsins and solid-state optics, has achieved the goal of millisecond-precision bidirectional control of defined cell types in freely behaving mammals. ChR2 was the first microbial opsin brought to neurobiology, where we initially found that ChR2-expressing neurons can fire blue light-triggered action potentials with millisecond precision, as a result of depolarizing cation flux, without addition of chemical cofactors; this approach has since proven versatile across a variety of preparations. Second, in work stimulated by the finding that the all-trans retinal chromophore required by microbial opsins appears already present within mammalian brains, so that no chemical cofactor need be supplied, we found that neurons targeted to express the light-activated chloride pump halorhodopsin from Natronomonas pharaonis (NpHR) can be hyperpolarized and inhibited from firing action potentials when exposed to yellow light in intact tissue and behaving animals; because of the excitation wavelength difference, the two optical gates can be simultaneously used in the same cells even in vivo5. Third, we employed genomic strategies to discover and adapt for neuroscience a third major optogenetic tool, namely a cation channel (VChR1) with action spectrum significantly redshifted relative to ChR2, to allow tests of the combinatorial interaction of cell types in circuit computation or behavior. Fourth, we have developed genetic targeting tools for versatile use of microbial opsins with existing resources including cell type-specific promoter fragments or Cre-LoxP mouse driver lines suitable for a wide variety of neuroscience investigations. Finally, we have developed integrated fiberoptic and solid-state optical approaches to provide the complementary technology to allow specific cell types, even deep within the brain, to be controlled in freely behaving mammals. Prof. Deisseroth is hosted by the students of the Department of Neurobiology, as a part of the departmental students-invited visiting scientist program.

Minerva-Weizmann Workshop on Active Sensing in Touch Vision and Smell

Conference
Date:
Tuesday, December 2, 2008
Hour:
Location:

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As Our Brain Is, So We Are

Lecture
Date:
Monday, December 1, 2008
Hour: 12:15
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Fred Travis
|
Center for Brain, Consciousness, and Cognition Maharishi University of Management, Fairfield, IA

Brain functioning underlies perception of outer objects and supports behavioral responses to environmental challenges. As brain circuits mature in the first 20 years of life, so mental abilities emerge. This talk will examine the relation between brain maturation—synaptogenesis and myelination— and levels of cognitive, moral, and ego development. Learning disabilities, such as ADHD and reading disabilities will be explored in light of associated brain patterns. Effects of experiences on brain functioning will also be examined including effects of restrictive experiences such as stress, drug use and fatigue, and enhancing experiences, such as Transcendental Meditation practice. High levels of human potential will be discussed in terms of enhanced brain functioning.

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.

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Timing and the olivo-cerebellar system

Lecture
Date:
Tuesday, June 17, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Prof. Yosef Yarom
|
Hebrew University of Jerusalem

The crystal-like anatomy and circuitry of the cerebellum and its preservation throughout vertebrate phylogeny suggest that it performs a single basic computation. It has been proposed that this basic computation is to create temporal patterns of activity necessary for timing motor, sensory and cognitive tasks. Despite the wide agreement about the involvement of the cerebellum in temporal coordination, there is an ongoing debate as to the neural mechanism that subserves this function. This debate stems from the current dogma that dominates cerebellar research. According to this dogma, PC simple spikes are evoked by input from granule cells and determine cerebellar nuclear (CN) activity, thus governing cerebellar output. The complex spikes, according to this view, serve as an error signal which is used by the system to readjust the simple spike activity. A novel theory of cerebellar function will be presented. According to this theory, the complex spike, rather than the simple spike, transmits the cerebellar output. The inferior olive generates accurate temporal patterns orchestrated by the cerebellar cortex and implemented in a variety of motor and non-motor tasks. Although this is a radical change of concept, it is well supported by experimental observations and it settles major problems inherent to the current dogma

Incubation of cocaine craving: behavioral and neuronal mechanisms

Lecture
Date:
Tuesday, June 10, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Dr. Yavin Shaham
|
National Institute on Drug Abuse, NIH

Abstract: Using a rat model of drug relapse and craving, we previously found time-dependent increases in cocaine seeking induced by exposure to drug cues after withdrawal from the drug, suggesting that cocaine craving incubates over time. In this lecture, I will first summarize our earlier behavioral and neurophysiological studies on incubation of cocaine craving. I will then discuss in more detail results from more recent studies implicating neuronal activity in the ventromedial prefrontal cortex and glutamate synaptic plasticity in the nucleus accumbens in the incubation of cocaine craving. I will also briefly address the relevance of our rat findings to the understanding of relapse to drug use in humans. Selected references related to incubation of cocaine craving Grimm JW, Hope B, Wise RA, Shaham Y (2001) Incubation of cocaine craving after withdrawal. Nature 412:141-142 Grimm JW, Lu L, Hayashi T, Su TP, Hope BT, Shaham Y (2003) Time dependent increases in brain-derived neurotrophic factor (BDNF) protein levels within the mesolimbic dopamine system following withdrawal from cocaine: implications for incubation of cocaine craving. The Journal of Neuroscience 23:742-747 Lu L, Dempsey J, Liu S, Bossert J, Shaham Y (2004) A single infusion of BDNF into the ventral tegmental area induces long-lasting potentiation of cocaine-seeking after withdrawal. The Journal of Neuroscience 24:1604-1611 Lu L, Grimm JW, Hope BT, Shaham Y (2004) Incubation of cocaine craving after withdrawal: a review of preclinical data. Neuropharmacology 47(S1): 214-227 (invited review for a special issue commemorating 30 years of NIDA research) Lu L, Hope BT, Dempsey J, Liu S, Bossert JM, Shaham Y (2005) Central amygdala ERK signaling pathway is critical to incubation of cocaine craving. Nature Neuroscience 8:212-219 Shaham Y, Hope BT (2005) The role of neuroadaptations in relapse to drug seeking. Nature Neuroscience 8:1437-1439 (special issue on Neurobiology of Addiction) Lu L, Uejima JL, Gray SM, Bossert JM, Shaham Y (2007) Systemic and central amygdala injections of the mGluR2/3 agonist LY379268 attenuate the expression of incubation of cocaine craving. Biological Psychiatry 61:591-598 Koya E, Uejima J, Wihbey K, Bossert JM, Hope BT, Shaham Y (2008) Role of ventral medial prefrontal cortex in incubation of cocaine craving. Neuropharmacology (in press, for a special issue commemorating 35 years of NIDA research)) Conrad KL, Tseng K, Uejima J, Reimers J, Heng L, Shaham Y, Marinelli M, Wolf ME (2008) Formation of accumbens GluR2-lacking AMPA receptors mediates incubation of cocaine craving. Nature (in press)

Single- and Double-Opponent Neurons in Primary Visual Cortex, and Their Different Roles in Color Perception

Lecture
Date:
Thursday, June 5, 2008
Hour: 13:30
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Robert Shapley
|
Center for Neural Science, New York University

Surrounding colors have a great influence on color perception. The reason is that the neural mechanisms of color perception need to make computations that take into account the spatial layout of the scene as well as the spectral reflectances of the target surface, in order to make color perception stable when illumination changes. It is not known how the visual system integrates form and color but it is now widely believed that the primary visual cortex, V1, plays an important role. Therefore, it is important to understand the spatial properties of V1 color-responsive neurons. Our investigations (in collaboration with Drs. Elizabeth Johnson and Michael Hawken) of color-responsive neurons in macaque monkey V1 revealed that there are two distinct groups of color-responsive cells in V1—single- and double-opponent cells—that have different functions in color perception. For example, V1 double-opponent cells are orientation-selective for pure color stimuli while single-opponent color cells are not. Double-opponent cells are selective for the spatial frequency of pure color stimuli while single-opponent color cells are very broadly tuned. The different types of color-responsive V1 cells probably both contribute to linking form and color, but in different ways.

Pain Selective Anesthesia

Lecture
Date:
Tuesday, June 3, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Dr. Alex Binshtok
|
Harvard Medical School, MA

Although pain is a complex entity, understanding the mechanisms of pain will reveal clues for better control. Perception of nociceptive, inflammatory and neuropathic pain - although initiated by distinctive mechanisms - all depend to some degree on generation and transmission of noxious signals by specific sets of primary sensory afferent neurons, nociceptors. Local anesthetics, by blocking voltage-gated sodium channels, prevent the transmission of nociceptive information and therefore block pain. However, since all local anesthetics act non-selectively on all types of axons, they also cause a loss of innocuous sensation, motor paralysis and autonomic block. Thus, approaches that produce only a selective blockade of pain fibers are of great potential clinical importance. In my talk, I will present a novel method to selectively block pain sensation. Using capsaicin to activate the TRPV1 channel, the noxious thermo-sensitive transducer localized specifically to high-threshold nociceptors, we were able to introduce QX-314, a membrane impermeable and therefore clinically ineffective lidocaine derivative, into nociceptors, and thereby blocked their electrical activity. Neurons that did not express TRPV1 were not blocked by the combination of QX-314 and capsaicin. Injection of QX-314 and capsaicin in vivo together but not alone abolished the response to noxious mechanical and thermal stimuli, without any motor or tactile deficit. This approach could be used clinically to produce long lasting regional analgesia while preserving motor and autonomic function. In addition to applications for dental procedures, surgery and childbirth, this technique could also be used to diminish postoperative and cancer pain, as well as inflammatory and neuropathic pain. Moreover, using TRP channels as a “natural” drug delivery system will enable specific cationic drugs to be targeted only to those cells that express the TRP channel. This technique offers a new strategy for treating pain.

Signal processing in neuronal networks: new vistas for calcium and noise

Lecture
Date:
Monday, June 2, 2008
Hour: 14:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Dr. Vladislav Volman
|
The Salk Institute

How neurons and neuronal networks perform signal processing tasks is one of the most important questions in neuroscience. Earlier research had focused on the integrative properties of individual neurons, and the role of activity-dependent inter-neuronal coupling remained obscure. We study the contribution of synaptic short-term plasticity to the detection, amplification, and storage of weak sensory stimuli in local neuronal circuits. Networks with fast plastic coupling show behavior consistent with stochastic resonance. Addition of slow asynchronous coupling mode leads to the qualitatively different properties of signal detection. Networks with asynchronous coupling also are able to hold information about the stimulus seconds after its cessation, thus representing a testable model of working memory, that is supported by experiments. Our results suggest a new, constructive, role in information processing for calcium-sustained synaptic “noise”.

Generation of dopamine neurons from embryonic stem cells for transplantation in Parkinson's disease

Lecture
Date:
Wednesday, May 28, 2008
Hour: 12:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Prof Anders Bjorklund
|
Lund University, Sweden

Fetal mesencephalic tissue has been used as a source of dopaminergic neurons for transplantation in clinical trials with Parkinson’s disease patients and in animal models of Parkinson’s disease. Due to the poor availability of human fetal tissue, and the ethical concerns associated with the use tissue from aborted fetuses, further development of the cell replacement therapy will critically depend on the access to alternative sources of cells for transplantation, based on the use of stem cells as a source of dopaminergic neurons. The recent discovery of Lmx1a and Msx1 as key determinant genes of mesencephalic dopaminergic neuron fate during development (Andersson et al. 2006) has opened new possibilities to drive undifferentiated stem cells towards fully functional mesencephalic dopaminergic neurons. Overexpression of these genes in stable embryonic stem (ES) cell lines is sufficient to generate neurons with almost 100% efficiency into a fully differentiated mesencephalic dopaminergic phenotype. The in vivo data obtained so far indicate that mesencephalic dopaminergic neurons can be generated in large numbers using this approach, and that they survive very well after transplantation to the striatum of 6-hydroxydopamine lesioned rats. In vivo, the Lmx1a- and Msx1-expressing cells develop into fully mature mesencephalic dopaminergic neurons, of both the A9 and A10 subtypes, and grow efficiently to form an extensive TH-positive axonal terminal network throughout the entire host striatum. Using this approach transplantable neurons with what appear to be a complete mesencephalic dopaminergic phenotype can be generated in large numbers from ES cell cultures.

Specialized mechanisms for face processing in the human brain

Lecture
Date:
Tuesday, May 27, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Dr. Galit Yovel
|
Tel Aviv University

It is well established that faces are processed by specialized mechanisms. I will first review evidence for the existence of face-specific processing mechanisms from cognitive studies, functional MRI and electrophysiology (Event-related potentials). These methods provide complementary information about the way information is processed in the brain. It is therefore important to determine whether they all reflect the same mechanism. Our data show that face-selective fMRI markers are strongly associated with cognitive markers of face-selective mechanisms. Furthermore, a simultaneous fMRI-ERP study reveals strong associations between face-selective fMRI regions and event-related potentials. Based on these findings, I will propose an integrated theory on how, where and when faces are represented at early stages of visual processing.

Does urocotin 1 matter?

Lecture
Date:
Monday, May 26, 2008
Hour: 12:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Prof. Tamas Kozicz
|
Dept of Cellular Animal Physiology Radboud University Nijmegen, The Netherlands

Interactions within the neurovascular unit underlying diseases of the cerebral cortex: evidence from human and animal studies

Lecture
Date:
Tuesday, May 20, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Prof. Alon Friedman
|
Ben Gurion University of the Negev

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.

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