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COGNITIVE DYSFUNCTION AND CHOLINERGIC ALTERATIONS PRIOR TO DOPAMINE LOSS IN MICE OVER-EXPRESSING WILD-TYPE HUMAN ALPHA-SYNUCLEIN
Lecture
Tuesday, December 20, 2011
Hour: 12:15
Location:
Gerhard M.J. Schmidt Lecture Hall
COGNITIVE DYSFUNCTION AND CHOLINERGIC ALTERATIONS PRIOR TO DOPAMINE LOSS IN MICE OVER-EXPRESSING WILD-TYPE HUMAN ALPHA-SYNUCLEIN
Dr. Iddo Magen
Dept of Neurology,
University of California at Los Angeles
Parkinson’s disease (PD) is a characterized, in addition to loss of dopaminergic neurons in the substantia nigra, by loss of cholinergic neurons in the basal nucleus (Zarow et al., 2003) and pathology of alpha-synuclein, a protein implicated in familial PD, in this region concurrently with pathology of alpha-synuclein pathology in the substantia nigra (Braak et al., 2003), as well as decrease in the activity of choline acetyltransferase, the rate limiting enzyme in the synthesis of acetylcholine (Ziabreva et al., 2006). Mild cognitive deficits are also observed in the early stages of PD (Elgh et al., 2009; Mamikonyan et al., 2009). Mice over-expressing the human wild-type alpha-synuclein under the Thy1 promoter (Thy1-aSyn) present progressive sensorimotor and non-motor behavioral abnormalities reminiscent of the pre-manifest early stages of PD (Magen and Chesselet, ’10) and subsequently exhibit a loss of striatal DA (Lam et al. ’11). We now examined whether these mice also exhibit cognitive deficits in tests sensitive to cholinergic function, and whether they present cholinergic deficits.
Thy1-aSyn mice on a mixed C57BL/6-DBA/2 background presented spatial working memory deficits in the Y-maze which showed progression from 3-4 to 5-6 months and to 7-9 months. Thy1-aSyn mice also showed spatial memory deficits in the novel place recognition test and recognition memory deficits in the novel object recognition test at 4-5 months of age. In a reversal learning task at 4-5 months, Thy1-aSyn mice learned the initial contingency rule as equally well as WT littermates, but were impaired in learning a reversal of this rule, mirroring the cognitive inflexibility displayed by early PD patients in similar tasks. Expression of both proteinase-K resistant and non-resistant alpha-synuclein in the medial septum and the basal nucleus, two major regions of cholinergic input into the forebrain, was increased in Thy1-aSyn mice at 5 months of age, and cholinergic neurons in both regions expressed both human and mouse alpha-synuclein in Thy1-aSyn mice, while endogenous (murine) alpha-synuclein expression was either lower or absent in cholinergic neurons in WT mice. However, morphological features of the cholinergic neurons such as cell body diameter did not change in either the basal nucleus or the septum. Acetylcholine levels decreased by 30% in the cortex of Thy1-aSyn mice at 6 months, further suggesting a link between acetylcholine pathology and the cognitive deficits.
Our data indicate that Thy1-aSyn mice display cognitive dysfunction at an early age, which is associated with decreased acetylcholine levels. As the cognitive tests used are sensitive to cholinergic function (Barker et al., 2008; Yang et al., 2009; Botton et al., 2010), future pharmacological studies will attempt to reverse these deficits using cholinergic agonists and/or acetylcholinesterase inhibitors. A study with an acute nicotine treatment is to be performed soon, to determine whether nicotine can reverse the cognitive deficits, which might point to a causal relation between the cognitive deficits and the compromised cholinergic system. In addition, the cognitive phenotype faithfully reproduces the early cognitive deficits in PD, whereas the lack of any neuropathology in cholinergic neurons suggests that the Thy1-aSyn models mild cognitive deficits rather than dementia, which is mostly associated with a gross neuropathology. Thus, it can serve as a basis for the testing of cognitive enhancers other than cholinergic agents.
Natural Vision Improvement
Lecture
Monday, December 19, 2011
Hour: 11:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Natural Vision Improvement
Meir Schneider
School for Self-Healing
San Francisco, CA
Toward a scientific understanding of subjective experience:an open discussion
Lecture
Thursday, December 15, 2011
Hour: 14:30
Location:
Camelia Botnar Building
Toward a scientific understanding of subjective experience:an open discussion
Prof. Giulio Tononi
Dept of Psychiatry,
University of Wisconsin
An integrated information theory of consciousness
Lecture
Wednesday, December 14, 2011
Hour: 14:30
Location:
Dolfi and Lola Ebner Auditorium
An integrated information theory of consciousness
Prof. Giulio Tononi
Department of Psychiatry
University of Wisconsin
Over the past decades, studies have investigated the neural correlates of consciousness with increasing precision. However, why experience is generated by the cortex and not the cerebellum, why it fades during certain stages of sleep and returns in others, or why some cortical areas endow experience with colors and others with sound, remains unexplained. Moreover, key questions remain unanswered. For example, how much consciousness is there when only a few brain 'islands' remain active? How much during sleepwalking or psychomotor seizures? Are newborns conscious, and to what extent?
Are animals conscious, how much, and in which way? Can a conscious machine be built? To address such questions, empirical observations need to be complemented by a principled theoretical approach. The information integration theory (IIT) has several related aims: to characterize, starting from phenomenology, what consciousness is and how each experience is structured; to account for several neurobiological observations about its neural substrate; and to develop measures of consciousness that can be applied, at least in principles, to humans, animals, and machines.
Automated In-vivo Phenotyping of Rodents – Towards PhenoWorld
Lecture
Wednesday, December 7, 2011
Hour: 12:15
Location:
Nella and Leon Benoziyo Building for Brain Research
Automated In-vivo Phenotyping of Rodents – Towards PhenoWorld
Dr. Walter Förster
TSE Systems International Group
Sculpting the mature nervous system:Nuclear receptors shape connections by controlling degeneration and regeneration during development
Lecture
Tuesday, December 6, 2011
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Sculpting the mature nervous system:Nuclear receptors shape connections by controlling degeneration and regeneration during development
Dr. Oren Schuldiner
Dept of Molecular Cell Biology, WIS
Adult neurons in the CNS undergo little or no regeneration following insults such as spinal cord injury. Their inability to regenerate results from both non-cell autonomous negative signals as well as from reduced internal growth capabilities. In contrast, developing neurons are capable of extensive growth, extension and reorganization. However, it has long been challenged whether growth events during development resemble the regenerative process following injury. In my talk I will present unpublished data regarding a new pathway that we discovered, consisting of a nuclear receptor complex regulating the mTor kinase, as crucial for a regenerative process during neuronal remodeling of the Drosophila mushroom body (MB) neurons. Importantly, these nuclear receptors are not important for the initial growth of these or other types of neurons. Therefore, we discovered a pathway that is selectively required for regeneration during development. I will also provide evidence that the worm ortholog of Hr51, one of the nuclear receptors we identified, is required for injury induced regeneration following axotomy. Therefore, our data uncover a novel pathway regulating regeneration during development and following injury and suggest that developmental and injury induced axon regeneration share molecular similarities.
Odor coding in awake mice
Lecture
Thursday, December 1, 2011
Hour: 12:15
Location:
Gerhard M.J. Schmidt Lecture Hall
Odor coding in awake mice
Dr. Roman Shusterman
Janelia Farm Research Campus, HHMI
Olfaction is traditionally considered a ‘slow’ sense, but recent evidence demonstrates that rodents are capable of making extremely difficult odor discriminations rapidly, in as little as a single sniff. To understand the temporal aspects of olfactory information processing, we studied how sniffing shapes the responses of mitral/tufted cells in awake mice. We found that odorants evoked precisely sniff-locked activity in mitral/tufted (M/T) cells in the olfactory bulb of awake mouse. The trial- to-trial response jitter averaged 12 ms, a precision comparable to other sensory systems. Individual cells expressed odor-specific temporal patterns of activity and responses were more tightly time-locked to the sniff phase than to the time after inhalation onset. Precise locking to sniff phase may facilitate ensemble coding by making synchrony relationships across neurons robust to variation in sniff rate. Additional feature that olfactory system should encode is odor intensity. Psychophysical experiments in humans demonstrate that perceived odor intensity falls rapidly with repeated sampling. Changes in perceived intensity can also be due to changes in odor concentration. We show that activity of M/T cells is a neural corelate of psychophysical phenomena.
Neurodegenerative diseases, stem cells and inflammation-new prospects for therapy
Conference
Thursday, December 1, 2011
Hour:
Location:
Dolfi and Lola Ebner Auditorium
Neurodegenerative diseases, stem cells and inflammation-new prospects for therapy
Bio-inspired Intracellular recordings and stimulation of neurons by extracellular multisite noninvasive gold mushroom shaped multi electrode array
Lecture
Tuesday, November 29, 2011
Hour: 12:30
Location:
The David Lopatie Hall of Graduate Studies
Bio-inspired Intracellular recordings and stimulation of neurons by extracellular multisite noninvasive gold mushroom shaped multi electrode array
Prof. Micha E. Spira
The Life Sciences Institute and the NanoCenter
The Hebrew University of Jerusalem
The development of Brain Machine Interface (BMI) technologies is driven by the belief that when successful such interfaces could be applied to replace damaged sensory organs (as the retina), replace motor part (limbs), link disrupted neuronal networks (injured spinal cord), generate hybrid neuro-electronic computers and others.
Despite decades of research and development, contemporary approaches fail to provide satisfying scientific concepts and technological solutions to generate efficient and durable interfaces between neurons and electronic devices. In the presentation I will describe a novel biologically inspired approach to enable the generation of efficient bidirectional electrical coupling between cultured neurons and extracellular multi-microelectrode array. The cell biological, molecular and physical principals underlying the novel neuroelectronic configuration will be explained.
The prospective of using our approach for long-term, non-invasive, multisite intracellular recording and stimulation for brain research and clinical BMI applications will be discussed.
Going into the Unknown, Together: Science and Improvisation Theatre
Lecture
Tuesday, November 22, 2011
Hour: 14:30
Location:
Dolfi and Lola Ebner Auditorium
Going into the Unknown, Together: Science and Improvisation Theatre
Prof. Uri Alon
Dept of Molecular Cell Biology, WIS
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Audio-visual objects
Lecture
Tuesday, May 31, 2011
Hour: 12:30
Location:
Jacob Ziskind Building
Audio-visual objects
Prof. Michael Kubovy
Psychology Dept
University of Virginia
In this talk I offer a theory of cross-modal objects. To begin, I will discuss two kinds of linkages between vision and audition. The first is a duality. The the visual system detects and identifies surfaces; the auditory system detects and identifies sources. Surfaces are illuminated by sources of light; sound is reflected off surfaces. However, the visual system discounts sources and the auditory system discounts surfaces. These and similar considerations lead to the Theory of Indispensable Attributes that states the conditions for the formation of gestalts in the two modalities. The second linkage involves the formation of audiovisual objects, integrated cross-modal experiences. I describe research that reveals the role of cross-modal causality in the formation of such objects. These experiments use the canonical example of a causal link between vision and audition: a visible impact that causes a percussive sound.
REGULATION OF HIPPOCAMPAL PLASTICITY: FROM DYNAMICS OF SINGLE SYNAPSES TO ALZHEIMER’S DISEASE
Lecture
Tuesday, May 24, 2011
Hour: 12:30
Location:
Jacob Ziskind Building
REGULATION OF HIPPOCAMPAL PLASTICITY: FROM DYNAMICS OF SINGLE SYNAPSES TO ALZHEIMER’S DISEASE
Dr. Inna Slutsky
Dept of Physiology and Pharmacology
Tel Aviv University
It is widely believed that memories are encoded and stored in the pattern and strength of synaptic connections. Individual synapses, the elementary units of information transfer, encode and store new information in response to the environmental changes through structural and functional reorganization. The key mechanisms that normally maintain plasticity of synapses and initiate synapse loss in neurodegenerative diseases remain elusive. To target this question, we developed an integrative approach to correlate structure and function at the level of single synapses in hippocampal circuits. Utilizing FRET spectroscopy, optical imaging, electrophysiology and molecular biology we explore the casual relationship between the pattern of ongoing neuronal activity, structural rearrangements within the synaptic signaling complexes and plasticity of single synapses and whole networks. Our results suggest that ongoing background synaptic activity critically determines the number and plasticity of synapses in hippocampal circuits.
Facial interactions in mammals
Lecture
Tuesday, May 17, 2011
Hour: 12:30
Location:
Jacob Ziskind Building
Facial interactions in mammals
Prof. Michael Brecht
Bernstein Center for Computational Neuroscience
Humboldt University Berlin
In the talk I will briefly remind the audience about the behavioral neuroscience of facial interactions in primates. I will then provide behavioral evidence for facial communication in rodents. Finally I will summarize our advances on the neurobiology of facial interactions in these animals.
Cellular and microcircuit analysis of spatial representations in the cortico-hippocampal system
Lecture
Monday, May 16, 2011
Hour: 12:30
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Cellular and microcircuit analysis of spatial representations in the cortico-hippocampal system
Prof. Michael Brecht
Extracellular recordings have elucidated spatial neural representations without identifying underlying microcircuits. We labeled neurons juxtacellularly in medial entorhinal cortex of freely-moving rats with a novel friction-based pipette-stabilization system. In a linear maze novel to the animals, spatial firing of superficial layer neurons was reminiscent of grid cell activity. Layer 2 stellate cells showed stronger theta-modulation than layer 3 neurons and both fired during the ascending phase of field potential theta. Deep layer neurons showed little or no activity. Layer 2 stellate cells resided in hundreds of small patches. At the dorso-medial border of medial entorhinal cortex we identified larger patches, which contained polarized head-direction selective neurons firing during the descending theta-phase. Three axon systems interconnected the patches: centrifugal axons from superficial cells to single large patches; centripetal axons from large patch cells to single small patches, and circumcurrent axons interconnecting large patches. Our microcircuit analysis during behavior reveals modularity of entorhinal processing. If time permits I will complement these findings from entorhinal cortex with data from hippocampal whole-cell recordings in awake behaving animals.
Predictive Sparse Coding:A Dynamical Circuit Model of Early Sensory Processing
Lecture
Wednesday, May 4, 2011
Hour: 12:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Predictive Sparse Coding:A Dynamical Circuit Model of Early Sensory Processing
Prof. Dmitri Chklovskii
Janelia Farm, HHMI, USA
In early sensory systems, such as retina and olfactory bulb in vertebrates or optic and antennal lobes in invertebrates, information about the world converges from a large number of receptors onto a much smaller number of projection neurons. Such bottleneck in the communication channel to the higher brain areas (Attneave, 1954, Barlow & Levick, 1976) can be overcome for sensory stimuli containing correlations by the predictive coding strategy (Srinivasan et al, 1982). In case of the retina, instantaneous subtraction of the least squares prediction compresses information and results in center-surround biphasic receptive fields. However, explaining variation of receptive fields with SNR (Srinivasan et al, 1982, Van Hateren, 1992, Atick & Redlich, 1990) would require circuit re-wiring which is unlikely on short time scales. Here we develop the predictive coding idea by proposing that a non-linear recurrent neuronal circuit can implement predictive coding adaptively: stimuli of different SNR result in different inhibitory surrounds. We solve the transient dynamics of this circuit in response to a step-like stimulus and demonstrate that it communicates a residual of the regularization path to higher brain areas. Thus, we are able to map a non-trivial computation on a concrete neuronal circuit and provide a theoretical framework to understand neural coding for many physiological experiments.
Flip sides of the same brain: Words and faces are both mediated by universal computational principles
Lecture
Wednesday, April 27, 2011
Hour: 12:30
Location:
Nella and Leon Benoziyo Building for Brain Research
Flip sides of the same brain: Words and faces are both mediated by universal computational principles
Prof. Marlene Behrmann
Carnegie Mellon University, Pittsburgh
Psychology/Center for the Neural Basis of Cognition
A key issue that continues to generate controversy concerns the nature of the psychological, computational and neural mechanisms that support the visual recognition of objects such as faces and words. While some researchers claim that visual recognition is accomplished by category-specific modules dedicated to processing distinct object classes, other researchers have argued for a more distributed system with only partially specialized cortical regions. Considerable evidence from both functional neuroimaging and neuropsychology would seem to favor the modular view, and yet close examination of those data reveal rather graded patterns of specialization that support a more distributed account. This talk presents theoretical and empirical data that explore a theoretical middle ground in which the functional specialization of brain regions arises from general principles and constraints on neural representation and learning that operate throughout cortex but that nonetheless have distinct implications for different classes of stimuli such as faces and words.
Microcircuit Dynamics in the Striatum
Lecture
Thursday, April 14, 2011
Hour: 12:30
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Microcircuit Dynamics in the Striatum
Gilad Silberberg
Assistant Professor,
Dept of Neuroscience
Karolinska Institute, Stockholm
Motor behaviour requires the meaningful integration of a multitude of sensory information. The basal ganglia are essential for such sensory-motor processing and underlie motor planning, performance, and learning. The striatum is the input layer of the basal ganglia, acting as a “hub” that receives glutamatergic and dopaminergic inputs from different brain regions. The intrastriatal microcircuit is a predominantly inhibitory GABAergic network comprised of a majority of projection neurons (medium spiny neurons, MSNs) and a minority of interneurons. In order to understand the operation of striatum it is essential to have a good description of the dynamic properties of the striatal microcicuitry and how it affects the activity striatal projection neurons. We use patch-clamp recordings in slice and in vivo combined with fluorescent microscopy and optogenetics to reveal the striatal microcircuit properties underlying sensorimotor processing
Mechanisms of axonal degeneration in health and disease
Lecture
Tuesday, April 12, 2011
Hour: 12:30
Location:
Jacob Ziskind Building
Mechanisms of axonal degeneration in health and disease
Dr. Avraham Yaron
Dept of Biological Chemistry, WIS
In the developing peripheral nervous system, many neurons die shortly after their axons have reached their target fields. This neuronal elimination serves as a mean to achieve a precise match between the number of neurons and the target innervation requirements. In addition, this process ensures that misguided axons, which do not reach their appropriate targets, will be eliminated. The regulation of this process is based on the limited production of various neurotrophic factors, insufficient to sustain the entire neuronal population. Since this loss usually occurs after the axons have already fully extended, some kind of axonal disintegration must escort the death of the cell body.
The talk will describe our efforts to uncover the mechanisms of axonal elimination during this process, and their relevance to axonal degeneration in pathological condition
Brain Sciences Open Day
Lecture
Monday, April 11, 2011
Hour: 09:30 - 14:00
Location:
Gerhard M.J. Schmidt Lecture Hall
Brain Sciences Open Day
Conscious Perception in USN
Lecture
Tuesday, April 5, 2011
Hour: 12:30
Location:
Jacob Ziskind Building
Conscious Perception in USN
Dr. Nachum Soroker
Dept of Neurological Rehabilitation, Loewenstein Hospital, Raanana,
and Sackler Faculty of Medicine
Tel Aviv University
Patients with right hemisphere damage often exhibit a symptom complex where contra-lesional objects and events fail to induce an appropriate behavioral reaction. The most puzzling aspect of this syndrome - termed unilateral spatial neglect (USN) - is the failure of salient left-sided stimuli to attract attention and generate conscious perception. This phenomenon, which is often multi-modal, may happen in cases where the sensory pathways and the primary cortical areas are completely intact. Following a short description of the clinical manifestations, underlying anatomy and recovery patterns of USN, I will present data gathered in a series of studies done in our hospital, which aimed to clarify the nature of processing received by stimuli on the neglected side, and the effect of some theory-motivated manipulations aimed to ameliorate the impaired processing.
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