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CARBOXYPEPTIDASE E: ROLE IN PEPTIDERGIC VESICLE TRANSPORT, NEUROPROTECTION AND CANCER
Lecture
Tuesday, October 28, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
CARBOXYPEPTIDASE E: ROLE IN PEPTIDERGIC VESICLE TRANSPORT, NEUROPROTECTION AND CANCER
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
Tuesday, October 7, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Population imaging in vivo: from the awake to the anesthetized
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
Tuesday, September 23, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Decoding conscious and unconscious mental states from brain activity in humans
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
Sunday, September 21, 2008
Hour:
Location:
Comparing spontaneous and stimulus-evoked activities in human sensory cortex
Lecture
Tuesday, September 16, 2008
Hour: 12:15
Location:
Nella and Leon Benoziyo Building for Brain Research
Comparing spontaneous and stimulus-evoked activities in human sensory cortex
Yuval Nir (Rafi Malach Group)
Department of Neurobiology, WIS
Traditionally, the brain and sensory cortex in particular have been viewed as being primarily driven by external events, but recent studies in anesthetized animals revealed robust spontaneous activity in sensory cortex, highlighting the intrinsic nature of brain processing. Using fMRI we found widespread slow fluctuations occurring spontaneously in the human visual cortex in the absence of external stimuli. These waves exhibited a consistent and specific neuro-anatomical distribution, suggesting that they largely reflect neuronal activity rather than hemodynamic noise sources. In further studies we obtained neurophysiological recordings in neurosurgical patients, and found direct electrophysiological evidence for such slow spontaneous neuronal fluctuation in human sensory cortex. These fluctuations were evident mainly in neuronal firing rates and in LFP gamma power changes, showed unique temporal dynamics following 1/f power laws, and were found to be correlated between corresponding ‘mirror’ sites across hemispheres within specific functional networks. Overall, these results extend previous animal studies of spontaneous activity by revealing and characterizing such activity in human sensory cortex.
Strong Loops in the Neocortex
Lecture
Wednesday, August 13, 2008
Hour: 12:15
Location:
Wolfson Building for Biological Research
Strong Loops in the Neocortex
Prof. Henry Kennedy
Dept of Integrative Neuroscience
INSERM, France
Hierarchy provides a major conceptual framework for understanding structure-function relationships of the cortex (Felleman and Van Essen, Cerb Cortex 1991). Feedforward (rostral directed) projections link areas in an ascending series and have a driving influence; feedback (caudal directed) projections link areas in a descending series and have a modulatory influence. This has led to the suggestion that feedforward projections are uniquely reciprocated by feedback projections i.e no strong loops (Crick and Koch, Nature 1998). We have re-examined this issue by making retrograde tracer injections in 22 areas spanning the occipital, parietal, temporal and frontal lobes. Injections were placed in areas V1, V2, V4 TEO, STPa, STPm, STPp, AudPba, AudPbp, 5, 7a, 7b, F1, 2, 8a, 45b, 9/46d, 9/46v, 46d, F5, ProM, 24c. High frequency sampling allows determination of indices of laminar distribution (SLN) and the relative strength (FLN) of connections (Vezoli et al., The Neuroscientist 2004). Analysis shows an inverse relationship between strength of connection and distance and revealed many (30%) hitherto unknown long-distance connections. Elsewhere we have shown that cortico-cortical projections form a smooth gradient: long-distance ascending connections are strongly feedforward (high SLN XX 100%) and on approaching the injection site have progressively lower SLN values (reaching 51%); likewise long-distance descending connections are strongly feedback (low SLN XX 0) and approaching the injection site reduce SLN 49% (Barone and Kennedy, J. Neurosci. 2000). The Felleman and Van Essen data is strictly hierarchical (no strong loops). A topological model of our data shows small world features (high cluster index and short average path distances) and five strong loops. Strong loops link frontal areas with occipital (areas 45-V4, 8A-V4), temporal (areas 45-TEO, 46-TEO) and parietal (areas 8A-7A, 46-7A) areas. The areas participating in strong loops exhibit high degrees of connectivity and constitute the hubs promoting small world attributes in the cortical architecture. The strong loops make it possible to go from V4 to all higher areas and back to V4 by uniqely feedforward pathways in an average of 3 and a maximum of 8 steps. One consequence of these anti-hierarchical connections is that the computations carried out in the supragranular layers of the cortex (Douglas and Martin, Annual Rev Neurosci. 2004) can be widely distributed in large-scale cortical networks mediating top-down control.
Extended Access to Self-Administered Cocaine –A Model for Cocaine Addiction
Lecture
Tuesday, August 12, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Extended Access to Self-Administered Cocaine –A Model for Cocaine Addiction
Dr. Osnat Ben-Shahar
Dept of Psychology
University of California Santa Barbara
Animal models used to study neuronal mechanisms of drug addiction most commonly rely upon either repeated experimenter-administered cocaine or drug-administration protocols that result in stable patterns of drug-taking. However, it is well established that differences in the route of administration (IV vs. IP or SC) and in the control over administration (self-administered vs. experimenter-administered) lead to differences in cocaine-induced neurochemical effects. In addition, the neural consequences of cocaine administration are different when tested in the middle of the administration protocol, immediately after the last administration of cocaine, or after 2, 14 or 60 days of withdrawal. Finally, the frequency and size of the daily-dose of cocaine are important factors determining the nature of the changes induced by cocaine. It would seem, then, that if we are to better understand the neuroadaptations that underlie the development of addiction in humans, animal models that mimic as closely as possible the human situation should be employed. Hence, my lab uses an animal model that employs an IV route of administration (as opposed to IP or SC), requiring self-administration (as opposed to experimenter-administered), under conditions (based on Ahmed & Koob, 1998) that distinguish the effects of short versus extended daily access to cocaine upon both behavior and neural substrates. This permits the investigation of neuroadaptations associated with the transition from the drug-naïve state to controlled drug-use, versus the further adaptations associated with the transition from controlled to compulsive drug-use. The differences we found, in both behavior and underlying neuronal adaptations, between controlled and compulsive drug-states, will be discussed in this talk.
Neural circuits for sensory-guided decisions in rats
Lecture
Monday, August 4, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Neural circuits for sensory-guided decisions in rats
Dr. Gidon Felsen
Cold Spring Harbor Laboratory
We are interested in how the nervous system controls movements based on sensory-cued spatial choices. To this end, we have been studying how rats use olfactory stimuli to select, initiate, execute, and evaluate directional movements. We reasoned that the superior colliculus (SC), a midbrain structure, could play a critical role in these processes, since it is known to be involved in several species in processing sensory input and producing orienting movements.
We tested this idea by using tetrodes to record simultaneously from several single neurons in the SC of rats performing a sensory-guided spatial choice task. In this task, an odor cue delivered at a central port determines whether water will be delivered upon entry into the left or right reward port. After sampling the odor, a well-trained rat will, in one fluid movement, withdraw from the odor port, orient left or right, and enter the selected reward port. This task thus requires that a freely moving animal make a spatial choice, while also affording reliable timing of task events and a large number of trials. In this context, not only did a substantial majority of SC neurons encode choice direction during a goal-directed movement, but many also predicted the upcoming choice, maintained selectivity for it after movement completion, or represented the trial outcome.
In order to determine whether the observed neural activity is causally related to the movement, we used the GABAA agonist muscimol to unilaterally inactivate the SC in rats performing the spatial choice task. If SC output were necessary for initiating contralateral movements, we would expect inactivation to bias the rat towards ipsilateral choices. Indeed, we found that muscimol, but not saline, biased the rat ipsilaterally, and this bias was dosage-dependent.
Our results demonstrate that the SC provides a rich representation of information relevant for several aspects of the control of orienting movements. These representations are necessary for executing appropriate movements. Together, these findings suggest a general role for the SC in behavior requiring sensory-guided navigation.
Hippocampal place field representation of the environment: Encoding, retrieval and remapping
Lecture
Tuesday, July 29, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Hippocampal place field representation of the environment: Encoding, retrieval and remapping
Prof. Etan Markus
University of Connecticut
When a rat runs through a familiar environment, the hippocampus retrieves a previously stored spatial representation of the environment. When the environment is modified a new representation is seen, presumably corresponding to the hippocampus encoding the new information. I will present single unit data on examining the issue of how the “hippocampus decides” whether to retrieve an old representation or form a new representation.
Visuo-Motor Mirror Neurons in Human Frontal and Temporal Lobes
Lecture
Tuesday, July 15, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Visuo-Motor Mirror Neurons in Human Frontal and Temporal Lobes
Dr. Roy Mukamel
UCLA
Recently, a unique population of neurons in the monkey ventral pre-motor cortex and in the rostral inferior parietal lobe, have been shown to respond during both execution of a goal-directed action and the perception of a goal-directed action performed by someone else. Since the activity of these motor neurons ‘reflects’ the perceived actions, these neurons have been termed mirror neurons. Due to their unique response properties, these neurons have been implicated in various behaviors such as imitation and empathy. Moreover, a dysfunction of this neural system has been implicated in various disorders such as autism. In humans, there is accumulating evidence from various techniques, supporting the existence of a parallel mirror neuron system however direct evidence is still lacking. We recorded extra-cellular activity of single neurons in medial pre-frontal and medial temporal regions of 23 epileptic patients while performing and observing hand movements and facial gestures. We found that 13.5% of the recorded neurons in both frontal and temporal lobes exhibited visuo-motor mirror properties. A subset of these mirror neurons responded with excitation action-observation and inhibition to action-execution suggesting a possible mechanism for inhibition of unwanted imitation. Our data supports a revision of the current definition of mirror neurons to include not only motor neurons that respond also to the perception of actions performed by others but also perceptual neurons in temporal lobe, responding to actions performed by oneself.
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Incubation of cocaine craving: behavioral and neuronal mechanisms
Lecture
Tuesday, June 10, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Incubation of cocaine craving: behavioral and neuronal mechanisms
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
Thursday, June 5, 2008
Hour: 13:30
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Single- and Double-Opponent Neurons in Primary Visual Cortex, and Their Different Roles in Color Perception
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
Tuesday, June 3, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Pain Selective Anesthesia
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
Monday, June 2, 2008
Hour: 14:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Signal processing in neuronal networks: new vistas for calcium and noise
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
Wednesday, May 28, 2008
Hour: 12:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Generation of dopamine neurons from embryonic stem cells for transplantation in Parkinson's disease
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
Tuesday, May 27, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Specialized mechanisms for face processing in the human brain
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
Monday, May 26, 2008
Hour: 12:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Does urocotin 1 matter?
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
Tuesday, May 20, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Interactions within the neurovascular unit underlying diseases of the cerebral cortex: evidence from human and animal studies
Prof. Alon Friedman
Ben Gurion University of the Negev
The Embryonic Neural Crest, from Specification to the Generation of Cellular Movement
Lecture
Tuesday, May 13, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
The Embryonic Neural Crest, from Specification to the Generation of Cellular Movement
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
Tuesday, May 6, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Plasticity in the circadian clock and social organization in bees
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.
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