Karel Svoboda

..The spread of Ras-dependent signaling was necessary for the local regulation of the threshold for LTP induction. Thus, Ca2+-dependent synaptic signals can spread to couple multiple synapses on short stretches of dendrite...

..Here we review the principles of 2PE microscopy, highlight recent applications, discuss its limitations, and point to areas for future research and development...

..New spines reconstructed using electron microscopy made synapses. Our data support a model in which outgrowth and enlargement of nascent spines is tightly coupled to formation and maturation of glutamatergic synapses...

..A large plasticity potential appears to be incorporated into these circuits, allowing for functional 'tuning' with fixed axonal and dendritic arbor geometry...

..Receptors in single spines depressed rapidly in an all-or-none manner. These adaptive changes in NMDA-R function likely play a critical role in metaplasticity and in stabilizing activity levels in neuronal networks with Hebbian synapses...

..Retrospective electron microscopy revealed that new boutons make synapses. Our data suggest that structural plasticity of axonal branches and boutons contributes to the remodeling of specific functional circuits...

..Our results are consistent with the hypothesis that auditory cortical microcircuitry is specialized to the one-dimensional representation of frequency in the auditory cortex...

..By 3 weeks, the strength of the L4-->L3 projection was similar to that of wild type. Our data indicate that Fmr1 shapes sensory cortical circuits during a developmental critical period...

..Our data indicate that novel sensory experience drives the stabilization of new spines on subclasses of cortical neurons. These synaptic changes probably underlie experience-dependent remodelling of specific neocortical circuits...

..Our data provide a causal link between new spine synapses and plasticity of adult cortical circuits and suggest that alphaCaMKII autophosphorylation plays a role in the stabilization but not formation of new spines...

..Depression of Ca2+ extrusion produces Ca2+ concentration dynamics that depend on the history of neuronal activity and therefore likely modulates the induction of synaptic plasticity...

..The cortico-cortical neurons in superficial layers of motor cortex thus couple motor and sensory signals and might mediate sensorimotor integration and motor learning...

..The coincidence of local input and LTS in the spine resulted in summation of local and global Ca2+ signals, a dendritic computation that could endow granule cells with subthreshold associative plasticity...

..In 6-month-old mice, spines turn over more slowly in visual compared to somatosensory cortex, possibly reflecting differences in the capacity for experience-dependent plasticity in these brain regions...

..We compared GECI fluorescence saturation with CaM Ca2+-dependent structural transitions. Our data suggest that GCaMP and Camgaroo2 report CaM structural transitions in the presence and absence of CaM-binding peptide, respectively...

..The entire dendritic and axonal arbor of individual neurons can be reconstructed...

..Synaptic strengths were reduced to compensate for extra synapses, keeping total synaptic input per neuron constant. Our data support a model in which synapse formation is promoted by actin-powered motility...

..Our data suggest that individual PSDs compete for PSD-95 and that the kinetic interactions between PSD molecules and PSDs are tuned to regulate PSD size...

..L2 neurons received input from lemniscal L3 cells and paralemniscal L5A cells spread over multiple columns. Our data indicate that lemniscal and paralemniscal information is segregated into interdigitated cortical layers...

..These local interactions between neighbouring synapses support clustered plasticity models of memory storage and could allow for the binding of behaviourally linked information on the same dendritic branch...

..Our findings reveal a fine-scale and dynamic organization of the frontal cortex that probably underlies flexible behaviour...

..Consistent with this, synaptic currents measured in layer 2/3 neurons at PND 8, just after these neurons ceased to migrate, revealed already spatially well-tuned receptive fields...

..Our data suggest that individual spines can regulate the subunit composition of their NMDA-Rs and the effective fractional Ca2+ current through these receptors...

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..Furthermore, the kinetics of Ca(2+) sources governs the time course of [Ca(2+)] signals and may explain the selective activation of long-term synaptic potentiation (LTP) and long-term depression (LTD) by NMDA-R-mediated synaptic Ca(2+)...

..Therefore, subcellular synapse targeting is independent of thalamic input and probably involves molecular labels and experience-independent forms of activity...

..Our results show that GCaMP2 is improved from the previous versions of GCaMP and may be suited to detect bursts of high-frequency action potentials and synaptic currents in vivo...

..Given the identical layer 1 territory upon which CR and TC axons grow, the differences in their structure and dynamics likely reflect distinct intrinsic growth programs for axons of long projection neurons versus local interneurons...

..The implication of a transiently inactivating calcium channel in synaptic release from granule cells suggests novel mechanisms for the regulation of lateral inhibition in the olfactory bulb...

..Given that L-type VSCCs do not contribute measurably to Ca2+ influx in spines, they must activate downstream effectors either directly through voltage-dependent conformational changes or via [Ca2+] microdomains...

..We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget...

..These results indicate that odor-evoked activity can have remarkable spatial specificity in the MB...

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..Our measurements suggest that sensory experience drives the formation and elimination of synapses and that these changes might underlie adaptive remodelling of neural circuits...

..Deprivation initiated at PND 15 had no effect on basal branching measured at PND 20. Thus the spatial organization of secondary dendritic branching is experience-dependent and shares a critical period with receptive field plasticity...

..Our measurements further demonstrate that optical recordings can be used to study single receptors in intact systems...

..Here, we describe techniques that are optimized for 2-photon imaging of [Ca2+] dynamics in small compartments such as dendrites and dendritic spines...

..Together with progress imaging synapses in vivo, the stage appears set for advances in understanding the dynamics and mechanisms of experience-dependent synaptogenesis...

..Other measures of excitability, including I-f curves and passive membrane properties, were affected by development but unaffected by whisker deprivation...

..In general, synaptic incorporation of AMPA-Rs in vivo conforms to rules identified in vitro and contributes to plasticity driven by natural stimuli in the mammalian brain...

..These results reveal competitive interactions between barrel and septal circuits in the establishment of precise intracortical circuits...

..In particular, recent work has highlighted that spines are highly specialized compartments for rapid large-amplitude Ca(2+) signals underlying the induction of synaptic plasticity...

..A major impediment to custom design is the difficulty of building custom data acquisition hardware and writing the complex software required to run the laser scanning microscope...

..The Ras pathway therefore functions as a supersensitive threshold detector for neural activity and Ca(2+) concentration...

..Our results show that perceptual decisions and learning can be driven by extremely brief epochs of cortical activity in a sparse subset of supragranular cortical pyramidal neurons...

..MISTs allow for specific, inducible, and reversible lesions in neuronal circuits and may provide treatment of disorders associated with neuronal hyperactivity...

..Automated analysis of dendritic spine morphology will enable objective analysis of large morphological data sets. The approaches presented here are generalizable to other aspects of neuronal morphology...

..In both hemispheres the L2/3-to-L5 projection is stronger than the L2/3-to-L2/3 projection. Our results suggest that laminar specificity may be identical for local and long-range cortical projections...

..We hope to end up with a core description of the function and plasticity of single synapses. ..

..We hope to end up with a core description of the function and plasticity of single synapses. ..

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..3.) Well-characterized systems will be introduced into subpopulations of neurons in mice using viruses and transgenic approaches. Systems will be tested in vivo using intrinsic signal imaging and electrophysiological techniques. ..

..We believe that Scanlmage will facilitate exciting biological discovery in numerous laboratories. ..

..We hope to end up with a core description of the function and plasticity of single synapses. ..

..These studies will be helped by improvements to existing instrumentation for TPLSM-based physiology in vivo. ..