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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.
Gateways to tactile perception: Parallel processing of pain and somatosensation
Lecture
Tuesday, July 8, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Gateways to tactile perception: Parallel processing of pain and somatosensation
Prof. Asaf Keller
University of Maryland
Vibrissal information is relayed to the barrel cortex through at least two parallel pathways: a lemniscal pathway involving the ventroposterior medial thalamic nucleus (VPM), and a paralemniscal pathway involving the posteromedial nucleus (POm). I will review the role of the lemniscal system, focusing on the mechanisms by which VPM shapes the response properties of neurons in cortical barrels. I will argue that although analyses of these properties (e.g. receptive field structure and angular preference) have illuminated the process of input transformation in sensory pathways, they may have only limited ethological role. I will show that this lemniscal pathway is critical for temporal coding of somatosensory inputs. In the paralemniscal pathway, and in POm in particular, neurons respond poorly and unreliably to physiologically relevant stimuli. I will show that the GABAergic nucleus zona incerta (ZI) regulates POm activity is a state-dependent manner. This regulation is mediated by the cholinergic activating system, which enhances POm activity during states of arousal and vigilance. However, even in these states, POm neurons fail to reliably encode sensory inputs. I will show that POm is critically involved in coding noxious stimuli. Specifically, I will present evidence in support of the hypothesis that the phenomenon of central pain may be the result of suppressed inhibitory regulation of POm activity.
DC Magnetic Fields Produced by the Human Body
Lecture
Thursday, July 3, 2008
Hour: 15:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
DC Magnetic Fields Produced by the Human Body
Prof. David Cohen
Biomag Group Leader (ret.), MIT Magnet Lab,& Assoc. Prof. of Radiology, Harvard Med. School
This is a review of measurements made mostly at the MIT Biomag Lab during the period of 1969 to 1983, partly in collaboration with Prof. Yoram Palti. These measurements are usually unique, in that their current sources are difficult to be seen with electric potentials. They are timely today because the new multi-channel SQUID systems are now being made capable of measuring DC fields from the head (and other organs). Our measurements were essentially a mapping over the whole body. DC fields were found almost everywhere, from many internal sources. They were larger over the limbs and head than over the torso proper, except over the abdomen, where it was largest. Over the head, there were puzzling signals from vicinity of healthy hair follicles, suggesting that so-called neural sources of the dcMEG could be overshadowed by more superficial sources. One major mechanism for generating these fields generally appeared to be a change in the K+ concentration in the vicinity of long excitable fibers. Overall, we concluded that DC fields are a rich and complex phenomena, including the dcMEG.
Information theory and the perception-action-cycle
Lecture
Tuesday, July 1, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Information theory and the perception-action-cycle
Prof. Naftali Tishby
School of Computer Science & Engineering and
Interdisciplinary Center for Neural Computation
The Hebrew University, Jerusalem
I will argue that living organisms can be characterized by their abilities to exchange information with their environment through sensing and acting. Moreover, the optimal interaction of an organism with its environment is determined by the information it can extract and store from the past about the future of its environment, on multiple time scales. Its optimal achievable performance is therefore bounded by the predictive-information of the environment, in some analogy with the entropy and channel-capacity bounds in Shannon's theory of communication. In that sense, life utilizes the predictability of its environment and act in order to increase its predictive capacity.
This conceptual and quantitative framework can allow us to design and analyze experiments in neuroscience in a new way. I will discuss some recent applications to auditory and motor physiology.
Wiring mechanisms in the mammalian somatosensory system
Lecture
Tuesday, June 24, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Wiring mechanisms in the mammalian somatosensory system
Prof. Avraham Yaron
Dept of Biological Chemistry, WIS
During development, the basic wiring of the nervous system is established by connecting trillions of neurons to their target cells. To reach their correct targets, neurons extend axons that are guided by cues in the extracellular environment.
The talk will describe our efforts to understand the mechanisms of axonal guidance using the somatosensory system as a model; with special focus on the role of the Semaphorins family of guidance cues in the process.
Grouping by synchrony and precise temporal patterns in the visual cortex: evidence from voltage-sensitive dye imaging
Lecture
Sunday, June 22, 2008
Hour: 10:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Grouping by synchrony and precise temporal patterns in the visual cortex: evidence from voltage-sensitive dye imaging
Dr. Hamutal Slovin
Bar Ilan University
Accumulating psychophysical and physiological evidence suggest the involvement of early visual areas in the process of visual integration and specifically in local facilitation of proximal and collinear stimuli. To investigate the early integration mechanisms at the population level, we performed voltage-sensitive dye imaging that is highly sensitive to subthreshold population activity, and imaged from the primary visual cortex (V1) and extrastriate cortex (V2) of a behaving monkey. The animal was trained on a simple fixation task while presented with collinear or non-collinear patterns of small gratings, Gabors or short oriented bars. Facilitation in terms of increased amplitude activity at the corresponding retinotopic site of the target was observed for low contrast targets presented as part of collinear or non-collinear pattern. The facilitation effect and its time course depended on the target flanker separation distance, suggesting the role of horizontal connections. Next, we compared the dynamics of cortical response. We found that the time course of responses increased faster in the collinear pattern as compared with the non-collinear pattern. Finally, to study synchronization, we calculated the spatial correlation of pixels at the target location and found that correlation was higher for the collinear pattern, suggesting that the neuronal code for collinear versus non-collinear pattern may be carried by synchronization and response dynamics rather than simply maximal amplitude of response.
These results suggest that neuronal population activity in area V1 is involved in local visual integration processes, and specifically in the increased sensitivity for low-contrast visual stimuli surrounded by high contrast flankers. In the second part of my talk I will discuss repeating spatio-precise spatio-temporal patterns. Numerous studies of neuronal coding have reported precise time relations among spikes in cortical neurons. Here our main goal was to study whether information processing in the cortex involves precise spatio-temporal patterns and to detect and characterize those patterns among neuronal populations exploiting voltage-sensitive dye imaging (VSDI) in visual cortical areas of a fixating monkey. Our preliminary results demonstrate that spatio-temporal patterns do exist above chance level (p<0.0001). The spatial characteristics of those patterns are consistent with physiological studies regarding the interplay between different visual areas, and the temporal characteristics show that the majority of the patterns appear in a range of 10-20ms apart
Timing and the olivo-cerebellar system
Lecture
Tuesday, June 17, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Timing and the olivo-cerebellar system
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
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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.
Rational therapeutic strategies for modifying Alzheimer's disease: Abeta oligomers as the validated target
Lecture
Monday, April 28, 2008
Hour: 11:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Rational therapeutic strategies for modifying Alzheimer's disease: Abeta oligomers as the validated target
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
Sunday, April 27, 2008
Hour: 10:30
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Medication Development for Treating Addiction: A New Strategy Focusing on the Brain's Dopamine D3 Receptor
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 – 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
Wednesday, April 16, 2008
Hour: 10:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Phenomenology of hypnosis
Dr. Alexander Solomonovich
Hypnosis Unit, Wolfson Medical Center
Astrocytes Regulation of Information Processing
Lecture
Tuesday, April 1, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Astrocytes Regulation of Information Processing
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
Tuesday, March 25, 2008
Hour: 10:00
Location:
Gerhard M.J. Schmidt Lecture Hall
Neurobiology of Mood Disorders: A developmental perspective
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
Tuesday, March 18, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Contrasting tuning properties of cortical and spinal neurons reveal distinct coding strategies
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).
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