All events, All years

How circadian clocks keep time: insights from Drosophila

Lecture
Date:
Tuesday, March 17, 2009
Hour: 12:30
Location:
Jacob Ziskind Building
Dr. Sebastian Kadener
|
Dept of Biological Chemistry The Hebrew University of Jerusalem

Circadian rhythms in locomotor activity are an example of a well-characterized behavior for which the molecular and neurobiological bases are not yet completely understood. These rhythms are self-sustained 24 hours rhythms that underlie most physiological and behavioral processes. The central circadian clock, which is situated in the brain, is responsible for daily rhythms in locomotor activity that persist even after weeks in constant darkness (DD). Peripheral clocks are spread trough the fly body and regulate a plethora of physiological functions that include: olfaction, detoxification and immunity. All these clocks keep time trough complex transcriptional-translational feedback loops that include the proteins CLK, CYC, PER and TIM. My research focuses on the study of the molecular basis of the circadian clock. In particular, I am interested in the contribution of the different molecular interactions and processes to the generation of robust 24hs rhythms. In this context, I have recently demonstrated that transcriptional speed of the clock gene PER is a determinant of the circadian period and that translational regulation by miRNAs is part of the central circadian clock.

Complex Translational Control in the Gustatory Cortex Determines the Stability of a Taste Memory

Lecture
Date:
Thursday, March 12, 2009
Hour: 12:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Dr. Kobi Rosenblum
|
Dept of Neurobiology, University of Haifa

The off-line processing of acquired sensory information in the mammalian cortex is an example for the unique way biology creates to compute and store information which guides behavior. The relatively short temporal phase in the process (i.e. hours following acquisition) is defined biochemically by its sensitivity to protein synthesis inhibitors. Until recently this negative definition of molecular consolidation did not reveal the details of the endogenous processes taking place, minutes to hours, in the neurons and circuit underlying a given memory. We use taste learning paradigms in order to study this process of molecular consolidation in the gustatory cortex. Recent results, from our laboratory, obtained from genetic, pharmacological, biochemical, electrophysiological and behavioral studies demonstrate that translational control, at the initiation and elongation phases of translation, plays a key role in the process of molecular consolidation. Moreover, this spatially and temporally regulated translation control modifies both general and synaptic protein expression that is crucial for memory stabilization. We propose a model to explain the interplay between regulation of initiation and elongation phases of translation and demonstrate that in certain situations cognitive enhancement can be achieved.

Unravelling signal processing in the cortical column

Lecture
Date:
Tuesday, February 24, 2009
Hour: 12:30
Location:
Jacob Ziskind Building
Prof. Idan Segev
|
Department of Neurobiology & Interdisciplinary Center for Neural Computation Hebrew University, Jerusalem

Never before have such intense experimental efforts been focused on neuronal circuits of the size of few hundred thousands neurons whose functions are relatively well defined. The extraordinarily powerful new genetic tools and 3D reconstruction methods, combined with modern multi-electrode arrays, telemetry, two-photon imaging and photo-activation are starting to shed bright light on the intricacies of these circuits, and in particular of the cortical column. But without tools that integrate all this different types of data, one cannot expect to gain a comprehensive understanding on how these circuits perform specific sensory-motor or cognitive functions. As in any other complex system, a modeling study is essential if we are to ever say that we understand how this system works. I will describe several attempts in my group to begin building detailed models of the cortical column, highlighting that, at both circuit level and at the level of individual neurons, models should capture experimental variability and that the building of these models should become automated. I will demonstrate how these models could be used to fruitfully guide new experiments and discuss were all this new integrated "simulation-driven brain research agenda" might lead to.

“Intersectional Optogenetics" unearths neurons that drive fish locomotion

Lecture
Date:
Wednesday, February 18, 2009
Hour: 15:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Ehud Isacoff
|
Dept of Molecular & Cell Biology UC Berkeley

A major challenge for biology is to develop new ways of determining how proteins operate in complexes in cells. This requires molecularly focused methods for dynamic interrogation and manipulation. An attractive approach is to use light as both input and output to probe molecular machines in cells. While there has been significant progress in optical detection of protein function, little advance has been made in remote control of any kind, including optical methods. As part of our efforts in the NIH Nanomedicine Development Center for the Optical Control of Biological Function, we are developing methods for rapidly switching on and off with light the function of select proteins in cells. The strategies are broadly applicable across protein classes. Our approach has been to synthesize Photoswitched Tethered Ligands (PTLs), which are attached in a site directed manner to a protein of interest. The site of attachment is designed into the protein to be at a precise distance from a binding site for the ligand. The geometric precision has two important consequences. First, light of two different wavelengths is used to isomerize the linker in such a way that the ligand can only bind in one of the sites, thus making it possible to toggle binding on and off with light. Second, native proteins are not affected by the PTL and remain insensitive to light, since the PTL does not attach. This means that a specific protein in a cell, a tissue and even in an intact freely behaving organism, can have its biochemical signaling turned on and off by remote optical control. The switching is very fast, taking place in ~1 millisecond, i.e. at the rate of the fastest nerve impulse. I will describe how we used our light-gated kaintate-type glutamate receptor, LiGluR, to study vertebrate locomotion. We used intersectional optogenetics in larval zebrafish to identify a new class of neurons that provide an important modulatory drive to swim behavior.

Computing as modeling

Lecture
Date:
Tuesday, February 17, 2009
Hour: 12:30
Location:
Nella and Leon Benoziyo Building for Brain Research
Prof. Oron Shagrir
|
Dept of Philosophy & Dept of Cognitive Science Hebrew University, Jerusalem

The view that the brain computes is a working hypothesis in cognitive and brain sciences. But what does it mean to say that a system computes? What distinguishes computing systems, such as brains, from non-computing systems, such as stomachs and tornadoes? I argue that a "structural" approach to computing cannot account for much of the computational work in cognitive neuroscience. Instead, I offer a modeling account, which is a variant of a "semantic" approach. On this modeling account, the key feature of computing is a similarity between the "inner" mathematical relations, defined over the representing states, and "outer" mathematical relations, defined over the represented states.

Changes in the brain during chronic nicotine: from thermodynamics to neuroadaptation

Lecture
Date:
Tuesday, February 17, 2009
Hour: 10:30
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Henry Lester
|
California Institute of Technology

The Development of Reading Pathways in School Age Children

Lecture
Date:
Thursday, February 12, 2009
Hour: 11:30
Location:
Nella and Leon Benoziyo Building for Brain Research
Dr. Michal Ben-Shachar
|
English Dept and the Gonda Brain Research Center Bar Ilan University

Learning to read involves exposure to large amounts of print in a focused period of time during childhood. How does this environmental transition affect cortical circuits for visual perception and shape recognition? I will present data from a developmental study of reading examining the relation between reading skill, cortical function and white matter properties in school age children. Functional properties in area MT+, and white matter properties in temporal callosal fibers, are both correlated with reading skill. I will discuss possible interpretations of these findings within a general model of the reading pathways.

Plasticity in the Human Ventral Stream:: Regional Differences Across Time Scales

Lecture
Date:
Monday, February 9, 2009
Hour: 12:30
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Kalanit Grill-Spector
|
Dept of Psychology & Neurosciences Institute Stanford University, CA

The human ventral stream consists of regions in the lateral and ventral aspects of the occipital and temporal lobes and is involved in visual recognition. One robust characteristic of selectivity in the adult human ventral stream is category selectivity. Category selectivity is manifested by both a regional preference to particular object categories, such as faces, places and bodyparts, as well as in specific (and reproducible) distributed response patterns across the ventral stream for different object categories. However, it is not well understood how experience modifies these representations and how do these representations come about throughout development. Here, I will describe two sets of experiments in which we addressed these important questions. First, I will describe experiments in adults in which we examined the effect of repetition on categorical responses in the ventral stream. Repeating objects decreases responses in the human ventral stream. However, repetition largely does not change the profile of category selectivity in the ventral stream, except for a place-selective region in the collateral sulcus in which long-lagged repetitions sharpened its responses. Second, I will describe experiments in which we examined changes in category selectivity throughout development from middle childhood (7-11 years), through adolescence (12-16) into adulthood. Surprisingly, we find that it takes more than a decade for the development of adult-like face and place-selective regions. In contrast, the lateral occipital object-selective region showed an adult-like profile by age 7. Finally, I will discuss the implications of these results on plasticity in the ventral stream and our theoretical models linking between fMRI measurements and the underlying neural mechanisms.

Neuronal Circuitry of Conditioned Fear

Lecture
Date:
Monday, February 2, 2009
Hour: 12:30
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Andreas Lüthi
|
Friedrich Miescher Institute, Switzerland

Fearful Brains in an Anxious World

Lecture
Date:
Sunday, February 1, 2009
Hour: 15:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Joseph E. Ledoux
|
Center for Neural Science, New York University

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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.

Comparing spontaneous and stimulus-evoked activities in human sensory cortex

Lecture
Date:
Tuesday, September 16, 2008
Hour: 12:15
Location:
Nella and Leon Benoziyo Building for Brain Research
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
Date:
Wednesday, August 13, 2008
Hour: 12:15
Location:
Wolfson Building for Biological Research
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
Date:
Tuesday, August 12, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
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
Date:
Monday, August 4, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
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
Date:
Tuesday, July 29, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
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
Date:
Tuesday, July 15, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
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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