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

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

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

Optogenetics: Application to Neuroscience and Neuropsychiatry

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

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

Optogenetics:Technology Development

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

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

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

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

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As Our Brain Is, So We Are

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

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

Role of dopamine systems in addiction

Lecture
Date:
Wednesday, November 26, 2008
Hour: 12:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Prof. Marco Diana
|
Laboratory of Cognitive Neuroscience Dept of Drug Sciences, University of Sassari, Italy

Dopamine neurons of the VTA, that project to the Nucleus Accumbens, have been involved in the initial rewarding properties of addicting compounds and, more appropriately, in the long-lasting changes observed after chronic drug administration and subsequent withdrawal. Indeed, alcohol, opiates cannabinoids and other substances provoke, upon withdrawal, a drastic and marked reduction of dopaminergic tone. In addition, aversive, non drug-related stimuli also reduce dopaminergic physiological tone. Furthermore, recent human studies reported an attenuated response to methylphenidate in alcoholic subjects and a lower (than controls) dopaminergic tone. These changes are paralleled by a lower number of D2 receptors and suggest a general “impoverishment” of dopamine transmission in the addicted brain. Accordingly, a dopamine deficit correlated with alcohol craving, which was associated with a high relapse risk. Similar results were reported for nicotine withdrawn rats. This hypodopaminergic state could be the target of therapies aimed at restoring the deficient dopamine transmission observed after chronic drug administration in preclinical and clinical investigations.

Interaction between the amygdala and the prefrontal cortex in emotional memory

Lecture
Date:
Tuesday, November 25, 2008
Hour: 12:30
Location:
Jacob Ziskind Building
Dr. Mouna Maroun
|
Department of Neurobiology and Ethology University of Haifa

The amygdala and the medial prefrontal cortex interact to guide emotional behavior. Alterations in the balance between these two structures can lead to persistent fear associations and to the development of anxiety disorders. In this talk I will present work from my laboratory studying the interaction between these two structures in normal conditions and when exposed to a fearful or stressful experience. We have recently found that fear and extinction learning induce differential changes in these two structures that could hint on the mechanisms by which these structures encode memories of fear and safety.

ON THE RELATIONSHIP BETWEEN MOTOR AND PERCEPTUAL BEHAVIOR –

Lecture
Date:
Wednesday, November 12, 2008
Hour: 12:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Dr. Andrei Gorea
|
Laboratoire Psychologie de la Perception CNRS & Paris Descartes University

Starting with Goodale & Milner's (1992) neuropsychological observations, a large number of neuropsychological and psychophysical studies has documented a putative dissociation between perception and action. However, a closer inspection of this literature reveals a number of methodological and conceptual shortcomings. I shall present a series of experiments making use of a variety of psychophysical techniques designed to gauge the relationship between Response Times as well Saccade Perturbations and observers' Perceptual States as assessed for not-masked and masked (metacontrast) stimuli via Yes/No, Temporal Order Judgments and Anticipation Response Times paradigms. All these studies reveal a strong action-perceptual state correlation indicating that motor and perceptual responses are based on a unique internal response. A one-path-two-decisions stochastic race model drawing on standard Signal Detection Theory provides a fair account of some of these data, hence overruling the necessity of a two-paths model of visual processing.

New insights into the hallmarks of obsessive-compulsive disorder (OCD): The prevalence of incompleteness and pessimal behavior

Lecture
Date:
Tuesday, November 11, 2008
Hour: 12:15
Location:
Jacob Ziskind Building
Prof. David Eilam
|
Dept of Zoology, Tel Aviv University

Performance of OCD patients was compared with that of matched normal individuals who were asked to perform the same task that the patients ascribed to their performance. Sequences of consecutive functional acts were long in controls and short in OCD, whereas sequences of non-functional acts were short in controls and long in OCD. Non-functional acts accumulated as a "tail" after the natural termination of the task, supporting the notion of incompleteness as an underling mechanism in OCD. It is suggested that the identified properties are consistent with a recent hypothesis that the individual's attention in OCD shifts from a normal focus on structured actions to a pathological attraction onto the processing of basic acts, a shift that invariably overtaxes memory. Such characteristics and mechanisms of compulsive rituals may prove useful in objective assessment of psychiatric disorders, behavioral therapy, and OCD nosology.

An embedded subnetwork of highly active neurons in the cortex

Lecture
Date:
Wednesday, November 5, 2008
Hour: 14:30
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Dr. Lina Yassin
|
Dept of Biological Sciences & Center for the Neural Basis of Cognition Carnegie Mellon University, Pittsburgh, PA

In vivo and in vitro, spontaneous and evoked neuronal activity are sparsely distributed across neocortical networks, where only a small subset of cells show firing rates greater than 1 Hz. Understanding the stability, network connectivity, and functional properties of this active subpopulation has been hampered by an inability to identify and characterize these neurons in vitro. Here we use expression of a fosGFP transgene to identify and characterize the properties of cells with a recent history of elevated activity. Neurons that had induced fosGFP expression in vivo maintained elevated firing rates in vitro over the course of many hours. Paired-cell recordings indicated that fosGFP+ neurons have a greater likelihood of being connected to each other, both directly and indirectly. These findings indicate that highly active neuronal ensembles are maintained over long time periods and suggest that specific, identifiable groups of neurons may dominate the way information is represented in the neocortex.

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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.

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
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
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

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