All events, All years

Imaging synaptic development and plasticity of adult-born neurons in the mouse Olfactory Bulb

Lecture
Date:
Monday, February 5, 2007
Hour: 12:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Dr. Adi Mizrahi
|
Department of Neurobiology, The Hebrew University of Jerusalem

The mammalian brain maintains few developmental niches where neurogenesis persists into adulthood. One niche is located within the olfactory system where the olfactory bulb (OB) continuously receives newborn neurons that integrate into the network as functional interneurons. However, little is known about the mechanisms of development and function of this unique population. In this study, we set out to directly image newborn neurons and synapses by combining high resolution in vivo two-photon microscopy and lentivirus labeling. Overexpressing cytosolic GFP or a synaptic protein (PSD95-GFP) reveals the general dendritic structure and/or synaptic distributions along dendritic trees, respectively. In vivo imaging reveals the dynamic behavior of dendrites and synapses over time. Adult-born neurons were transduced at the subventricular zone and imaged in the OB where they start to mature into functional neurons. First, time-lapse imaging of newborn neurons over several days revealed that dendritic formation is highly dynamic with distinct dynamics for spiny neurons and non-spiny neurons. The dynamic nature of newborn development was not affected by sensory deprivation. Once incorporated into the network, adult-born neurons maintain significant levels of structural dynamics. This structural plasticity is local, cumulative and sustained in neurons several months after their integration. Second, synapse formation on these young cells and dendrites was verified by EM analysis of PSD95-GFP expressing cells. Using these neurons we found that early during development, synaptic distributions are highly ordered along dendritic trees. Third, these synapses continuously change locations along dendritic shafts as revealed time-lapse imaging over several days. Interestingly, these newborn neurons remain structurally dynamic months after they have been incorporated into the network. I will also discuss preliminary results where we use in vivo calcium to decipher the physiological activity of unique populations in the OB and cortex. These experiments provide an experimental model to directly study the dynamics of neuronal and synaptic development in the intact mammalian brain and provide direct evidence for the ongoing plasticity of the adult-born neuronal population.

Structure and dynamics of neuronal networks: impact on representation

Lecture
Date:
Monday, January 29, 2007
Hour: 12:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Prof. Shimon Marom
|
Dept of Physiology, Faculty of Medicine, Technion

The structure of large random networks is explored using spontaneous and evoked activities recorded from a subset of individual neurons. The emerging topology is that of a complex dynamic graph. Impacts on concepts of representation are analyzed.

Spatial processing in the auditory brainstem-new roles for synaptic inhibition

Lecture
Date:
Thursday, January 25, 2007
Hour: 12:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Prof. Benedikt Grothe
|
Ludwig Maximilians University, Munich, Germany

The arrival times of a sound at the two ears are only microseconds apart, but both birds and mammals can use these interaural time differences to localize low-frequency sounds. Traditionally, it was thought that the underlying mechanism involved only coincidence detection of excitatory inputs from the two ears. However, recent findings have uncovered profound roles for synaptic inhibition in the processing of interaural time differences. In mammals, exquisitely timed hyperpolarizing inhibition adjusts the temporal sensitivity of coincidence detector neurons to the physiologically relevant range of interaural time differences. Inhibition onto bird coincidence detectors, by contrast, is depolarizing and devoid of temporal information, providing a mechanism for gain control.

Conflict resolution: a monkey fMRI study

Lecture
Date:
Tuesday, January 23, 2007
Hour: 12:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Dr. Maria de la O Olmedo Babe
|
Brain Research Institute, University of Bremen, Germany

fMRI is a technique that allows us to observe brain function; from a small group of neurons to the whole brain and from attentional or perceptual basic mechanisms to high executive functions. Conflict resolution is an executive function that allows to process constantly new information and react according to the needs of the situation. Stroop, Simon and Flanker effects in humans are well described in the literature (Stroop, 1935, Pardo, 1990, Wittfoth, 2006). In order to investigate the neural bases, two monkeys were trained in tasks that involve conflict resolution. Stimulus arrangement was chosen such as to investigate Stroop, Simon and Flanker effects by analyses of behavioral and imaging data.

Computational physiology of the high frequency discharge and pauses of basal ganglia neurons

Lecture
Date:
Monday, January 15, 2007
Hour: 12:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Prof. Hagai Bergman
|
Department of Physiology, Faculty of Medicine, The Hebrew University of Jerusalem

The neurons of many basal ganglia nuclei, including the external and internal globus pallidus (GPe, GPi respectively) and the substantia nigra pars reticulta (SNr) are characterized by their high-frequency (50-100 spikes/s) tonic discharge (HFD). However, the high firing rate of GPe neurons is interrupted by long pauses. To provide insight into the GPe pause physiology, we developed an objective criterion for the quality of the isolation of extracellularly recorded spikes and studied the spiking activity of 212 well-isolated HFD GPe and 52 GPi/SNr neurons from five monkeys during different states of behavioral activity. An algorithm which maximizes the surprise function was used to detect pauses and pauser-cells ("pausers"). Only 6% of the GPi/SNr neurons vs. as many as 56% of the GPe neurons were classified as pausers. The average pause duration equals 0.6s and follows a Poissonian distribution with a frequency of 13 pauses/minute. No linear relation was found between pause parameters (duration or frequency) and the firing rate of the cell. Pauses were preceded by various changes in firing rate but not dominantly by a decrease. The average amplitude and duration of the spike waveform was modulated only after the pause but not before it. Pauses of pairs of cells which were recorded simultaneously were not correlated. The probability of GPe cells to pause spontaneously was extremely variable among monkeys (30-90%) and inversely related to the degree of the monkey's motor activity. These findings suggest that spontaneous GPe pauses are neither triggered by an intrinsic cellular mechanism nor by slow global changes in the extracellular medium and probably reflect a network property of the basal ganglia related to low-arousal and network exploration periods.

Conversion of sensory signals into perceptual decisions

Lecture
Date:
Monday, January 8, 2007
Hour: 14:00
Location:
Arthur and Rochelle Belfer Building for Biomedical Research
Prof. Ranulfo Romo
|
National Autonomous University of Mexico

Multi-regional Interactions support memory formation: modulation of the Rhinal cortices by the Amygdala and the mPFC

Lecture
Date:
Monday, January 8, 2007
Hour: 12:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Dr. Rony Paz
|
Center for Molecular & Behavioral Neuroscience, Rutgert University, New-Jersey

When is it worth working: Behavioral, physiological, genetic, and modeling experiments investigating motivation and reward expectancy

Lecture
Date:
Sunday, January 7, 2007
Hour: 10:00 - 11:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Dr. Barry J. Richmond
|
Chief, Section on Neural Coding and Computation Laboratory of Neuropsychology, National Institute of Mental Health, NIH, DHHS, USA

The intensity or vigor of goal-directed behavior is a correlate of the motivation underlying it. Motivation is related to the subjective value of rewards and is moderated, or even completely dissipated, if the perceived effort or discomfort seems too great. Under what circumstances do we seek a goal or a reward? To study motivated behavior in monkeys, we use several variants of a task in which monkeys must perform some work, in this case detecting when a target spot turns from red-to-green, to obtain a drop of juice. We use another visual stimulus, a cue, to indicate how much discomfort must be endured, e.g., the number of trials to be worked, to obtain the reward. The monkeys learn about the cues quickly, often after just a few trials. The number of errors becomes proportional to amount of work remaining before reward, achieving our goal of manipulating motivation. This is a behavior in which the monkeys decrease their performance in response to an increased predicted workload. Temporal difference models have provided an important framework for interpreting goal directed-behavior, and in economics, game theory has been used to model choice behavior. A key concept in these models is to determine how the value of the reward is modulated by some parameter of the experiment, such as changing the reward size, or the amount of time needed to obtain the reward. In learning or adaptation the TD algorithm predicts that behavior should be (and in artificial systems is) adapted to maximize long-term reward. By examining the influence of reward size, waiting time, and amount of work, we can examine in what ways different model succeed and fail. Our data show that performances depend on work completed since preceding reward (sunk cost effect), and accumulated reward (over whole sessions) and work. In addition this behavior can be used to learn about categorization and rule learning. Using single neuronal recording, regional ablation, and molecular ablation of the D2 receptor we show that dopamine-rich brain regions have signals related to the balance between reward and work.

Stress and the Brain – a Molecular View

Lecture
Date:
Tuesday, January 2, 2007
Hour: 12:00 - 13:15
Location:
Nella and Leon Benoziyo Building for Brain Research
Dr. Daniela Kaufer
|
Department of Integrative Biology Helen Wills Neuroscience Institute, University of California Berkeley, CA

My lab studies the molecular basis of neural and hormonal mechanisms of stress responses. Using interdisciplinary multilevel approach we look at the plasticity of the brain in dealing with physiological and pathological events. In this talk I will describe three current projects: Hormonal Regulation of Neural Stem Cells. Determining the environmental and internal cues that control the proliferation and fate choices of stem cells in the adult hippocampus, and their role in functional plasticity. RNA Regulatory Mechanisms in Neural Stress Responses. RNA regulation, specifically, alternative splicing and microRNA expression as a fine tuning neural stress mechanism. The Molecular Mechanisms of post-trauma Epileptogenesis. Determine the mechanism underlying epileptogenesis following blood brain barrier damage.

Synaptic maintenance - Insights from live imaging experiments

Lecture
Date:
Monday, January 1, 2007
Hour: 12:00
Location:
Nella and Leon Benoziyo Building for Brain Research
Dr. Noam Ziv
|
Dept of Physiology, Faculty of Medicine, Technion

Recent studies suggest that central nervous system (CNS) synapses persist for many weeks, months and even lifetimes, yet little is known on the mechanisms that allow these structures to persist for so long despite the many deconstructive processes acting at biological systems and neurons in particular. As a step toward a better understanding of synaptic maintenance we set out to examine some of the deconstructive and reconstructive forces acting at individual CNS synapses. To that end we studied the molecular dynamics of several presynaptic and postsynaptic cytomatrix molecules. Fluorescence recovery after photobleaching (FRAP) and photoactivation experiments revealed that these molecules are continuously incorporated into and lost from individual synaptic structures within tens of minutes. Moreover, these dynamics can be accelerated by synaptic activity. Finally, we find that synaptic molecules are continuously exchanged between nearby synaptic structures at similar rates and that these rates greatly exceed the rates at which synapses are replenished with molecules arriving from somatic sources. Our findings indicate that the dynamics of key synaptic matrix molecules may be dominated by local protein exchange and redistribution, whereas protein synthesis and degradation serve to maintain and regulate the sizes of local, shared pools of these proteins. The nature of these dynamics raises intriguing questions as to how synapses manage to maintain their individual, use-dependent structural and functional characteristics over long durations.

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