All events, All years

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.

Gateways to tactile perception: Parallel processing of pain and somatosensation

Lecture
Date:
Tuesday, July 8, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
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
Date:
Thursday, July 3, 2008
Hour: 15:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
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
Date:
Tuesday, July 1, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
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
Date:
Tuesday, June 24, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Dr. 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
Date:
Sunday, June 22, 2008
Hour: 10:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
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
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

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Information-theoretic analysis of neural data: why do it, why it is challenging, and what can be learned

Lecture
Date:
Tuesday, February 5, 2008
Hour: 12:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Jonathan Victor
|
Cornell University

Entropy and information are quantities of interest to neuroscientists, because of their mathematical properties and because they place limits on the performance of a neural system. However, estimating these quantities from neural spike trains is much more challenging than estimating other statistics, such as mean and variance. The central difficulty in estimating information is tightly linked to the properties of information that make it a desirable quantity to estimate. To surmount this fundamental difficulty, most approaches to estimation of information rely (perhaps implicitly) on a model for how spike trains are related. But the nature of these model assumptions vary widely. As a result, information estimates are useful not only in situations in which several approaches provide mutually consistent results, but also in situations in which they differ. These ideas are illustrated with examples from the visual and gustatory systems.

Consequences of the uncertainty principle of measurement for perception and action

Lecture
Date:
Wednesday, January 30, 2008
Hour: 13:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Dr. Sergei Gepshtein
|
Brain Science Institute, RIKEN, Japan The Salk Institute for Biological Studies, USA

What can we learn from the octopus about the evolution of neural system for learning and memory?

Lecture
Date:
Tuesday, January 29, 2008
Hour: 12:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Dr. Binyamin Hochner
|
Hebrew University, Jerusalem

The octopus is an active hunter, a remarkable invertebrate whose complex behaviors rely on exceptionally good visual and tactile senses coupled with highly advanced learning and memory (LM) abilities. Studying the octopus LM system may therefore reveal characteristics universally important for mediation of complex behaviors. We developed slice and isolated brain preparations of the LM area in the octopus brain to characterize the short- and long-term neural plasticity. The importance of these processes for LM are been tested in behavioral experiments. The results support the importance of LTP in behavioral LM and suggest new ideas regarding the organization of short- and long-term memory systems.

Decoding neural signals for the control of movement

Lecture
Date:
Tuesday, January 22, 2008
Hour: 12:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Sara Solla
|
Northwestern University

The activity of neurons in primary motor cortex provides the signals that control our ability to execute movements. One of the crucial questions, still unresolved, is that of identifying the coordinate system used in the execution of movements: is it an Euclidean representation of the external space, or an actuator representation of the state of the muscles? We address this question through the analysis of data obtained for an awake behaving monkey. The data includes simultaneous recording of the activity of about one hundred neurons in motor cortex and of the activity of about ten muscles in the relevant limb. The analysis of this data involves a variety of techniques, from linear regression models to nonlinear methods for dimensionality reduction. I will review the current level of achievement in this active area of research and discuss its implications, both for understanding aspects of neural information processing that relate to natural behaviors and for extracting from these neural signals the information needed to guide prosthetic limbs and other types of external devices.

Cortical Maps, Dyanamic Innformation Processing and Perception

Lecture
Date:
Monday, January 21, 2008
Hour: 13:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Christopher Moore
|
McGovern Institute for Brain Research, MIT

I am interested in how neural dynamics, changes in neural sensitivity on the time scale of milliseconds to seconds, support rapid changes in perceptual capability. Our key focus is in testing the hypothesis that dynamics in early sensory cortices, such as the primary somatosensory cortex, play a key role in perception. To examine these issues in a model where detailed invasive studies are possible, we study the vibrissa sensory system of rodents. To examine the broader relevance of these findings, we have a smaller parallel effort I human perception and imaging. A variety of our studies suggest that. In this seminar, I will describe work we have done to understand the 'natural scene' of vibrissa perception, the signals that are generated during active surface contact. I will then describe how these signals are encoded in 2 recently discovered cortical maps, a frequency map, shaped by the resonance properties of the vibrissae, and a direction map, encoding the angle of vibrissa motion. I will then discuss why having these cortical feature columns, with adjacent neurons sharing similar computational processing, may enhance information processing. Specifically, I will argue that this arrangement facilitates dynamic regulation of neural sensitivity by neuromodulators that have a more course spatial precision, on the order of 300-1000 microns. I will briefly mention the hemo-neural hypothesis, the proposal that changes in blood flow and volume may be one source of neural regulation on this spatial scale. I will then describe an example of the dynamic regulation of spatial activation across a cortical map, resulting from adaptation during robust thalamocortical input at 5-25 Hz. I will argue that this adaptation leads to a transition into a state that is enhanced for discrimination of alternative stimuli, but impoverished for detection of novel stimuli (decreased sensitivity). To test the hypothesis that these kinds of cortical dynamics in the primary somatosensory cortex regulate perception, I will describe human MEG experiments showing that changes in the amplitude of SI activation regulate detection probability, and showing that these changes in perception and cortical amplitude are predicted by ongoing rhythmic activity in human SI at 5-25 Hz (the 'mu' rhythm).

Neural Circuits Underlying Sexually Dimorphic Social and Reproductive Behaviors

Lecture
Date:
Wednesday, January 16, 2008
Hour: 12:00
Location:
Dolfi and Lola Ebner Auditorium
Dr. Tali Kimchi
|
Department of Molecular and Cellular Biology Harvard University

My long term interest lies in the mechanistic understanding of sensory processes underlying behavioral responses in laboratory as well as natural wild environments. External sensory cues control complex behaviors such as mating, predator avoidance or orientation in space that are essential for the animal survival and the propagation of the species. In rodents, pheromones play a major role in controlling innate social and sexual responses including mating, nursing and aggression. However, although these behaviors display striking sexual dimorphisms, surprisingly few anatomical and molecular features have been identified that differentiate the male from the female brain. Using genetic and behavioral tools, I have shown that the vomeronasal organ (VNO), an olfactory sensory organ in the nasal cavity of many mammals which detects pheromones, is responsible for the control of male- and female-specific social and sexual behaviors. Amazingly, female mice in which the VNO has been genetically or surgically inactivated engage in male-typical courtship and sexual behaviors including mounting, pelvic thrusting and courtship vocalization, that are indistinguishable from that of normal male mice. These findings suggest a model in which male and female circuits that regulate innate reproductive behaviors exist in the brain of both sexes, while a sex-specific chemosensory network enables pheromonal cues to control the sex-specificity of behavior. To gain a deeper understanding of the molecular and neuronal processes underling sex-specific innate behaviors my lab will combine molecular and genetic tools, together with unique behavioral approaches, to study animal behavioral responses under natural ethologically relevant conditions. Furthermore, to uncover novel VNO-mediated pheromone responses that might have degenerated or been suppressed in inbred laboratory mouse lines, wild-caught mouse strains will be studied in wide range of behavioral, genetically and physiological assays.

Who's Afraid of Chaotic Networks? Model of Sensory and Motor Processing in the Face of Spontaneous Neuronal Activity

Lecture
Date:
Tuesday, January 15, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Prof. Larry Abbott
|
Columbia University

Large, strongly coupled neural networks tend to produce chaotic spontaneous activity. This might appear to make them unsuitable for generating reliable sensory responses or repeatable motor patterns. However, this is not the case. Inputs can induce a phase transition, leading to responses uncontaminated by chaotic "noise". Likewise, appropriately trained feedback units can control the chaos, resulting in a wide variety of repeatable output patterns. These issues will be discussed accompanied by examples and demonstrations.

Beyond Hebbian Plasticity – A Dynamic View of Memory Processing

Lecture
Date:
Monday, January 14, 2008
Hour: 13:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Karim Nader
|
Psychology Dept, McGill University, Montreal

Memory scientists have been inspired and directed for decades in their search for brain mechanisms mediating learning and memory by the postulates of D.O. Hebb. Two of Hebb's most influential postulates include that co-incident activation of pre-and post-synaptic cells could be a mechanism for learning (Hebbian/associative long term potentiation). In addition once a memory is aquired, it initially exists in a fragile, labile state, after which it becomes stabilized/consolidated in the brain. While these postulates have been incredibly influential and largely correct, the data suggests it is may be time to move beyond these postulates. Data will be presented to demonstrate that synapses may not be sensitive to co-incidence of pre- and post-synaptic activation, rather they may be sensitive to probability of their co-activation. Second, we demonstrate that even old consolidated memories return to a labile state when they are remember, and must be reconsolidated in order to persist. This suggests that the traditional Consolidation Hypotheses, including Hebb's postulates, are no longer sufficient to explain the data.

Motor learning with unstable neural representations

Lecture
Date:
Wednesday, January 9, 2008
Hour: 11:30
Location:
Wolfson Building for Biological Research
Dr. Uri Rokhni
|
MIT

It is usually assumed that the brain learns by changing neural circuits that are otherwise stable. However, recent experiments in monkeys show that the neural representation of movement in motor cortex is continually changing even without learning, when practicing a familiar task. We set to investigate the reason for these changes. We analyzed the empirical data and found that the changes are slow and random. We constructed a theoretical model of a cortical network that learns a motor skill by changing synaptic strengths. Our model explains how the network can change its synaptic strengths, and neural activity, without changing the motor behavior. Additionally, our model replicates the observed changes when synaptic learning is assumed highly noisy. We speculate that this noise serves to explore different synaptic configurations during learning.

TRP channels, what are they and why are they important

Lecture
Date:
Tuesday, January 8, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Prof. Baruch Minke
|
Hebrew University, Jeruslaem

TRP channels constitute a large and diverse family of proteins that are expressed in many tissues and cell types. The TRP superfamily is conserved throughout evolution from nematodes to humans. The name TRP is derived from a spontaneously occurring Drosophila mutant lacking TRP that responded to a continuous light with a Transient Receptor Potential (therefore, it was designated TRP by Minke). The Drosophila TRP and TRP-like (TRPL) channels, which are activated by the inositol lipid signaling cascade, were used later on to isolate the first mammalian TRP homologues. TRP channels mediate responses to light, nerve growth factors, pheromones, olfaction, taste, mechanical, temperature, pH, osmolarity, vasorelaxation of blood vessels, metabolic stress and pain. Furthermore, mutations in members of the TRP family are responsible for several diseases. Although a great deal is known today about members of the mammalian TRP channels, the exact physiological function and gating mechanisms of most channels are still elusive. Removal of divalent open channel block by depolarization plays a critical role in learning and memory, which is mediated by the N-methyl-D-aspartate (NMDA) channel. TRP channels also exhibit open channel block, but the physiological mechanism of its removal is still unknown. We found that lipids produced by phospholipase C (PLC) and hypoosmotic solutions remove divalent open channel block from the Drosophila TRPL channels without depolarization. Application of lipids increased single channel current and caused impermeable cation influx. The tarantula peptide GsMTx-4 specifically blocks a range of stretch-activated channels, but not by specific interaction with the channel proteins themselves but rather by modification of the channel-lipid boundary. The GsMTx-4 toxin blocked the lipids effect on TRPL channels. We found remarkable commonality between the effects of lipids on the Drosophila TRPL and the mammalian NMDA channels. We suggest a new lipid-dependent mechanism to alleviate open channel block, which operates under physiological conditions, in synergism with depolarization. The profound effect of lipids modulation allows cross talk between channel activity and lipid-producing pathways. Joint work with Moshe Parnas, Ben Katz & Shaya Lev

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