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2 Publications

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    Karpova LabSvoboda Lab
    12/08/05 | Rapid and reversible chemical inactivation of synaptic transmission in genetically targeted neurons.
    Karpova AY, Tervo DG, Gray NW, Svoboda K
    Neuron. 2005 Dec 8;48(5):727-35. doi: 10.1016/j.neuron.2005.11.015

    Inducible and reversible silencing of selected neurons in vivo is critical to understanding the structure and dynamics of brain circuits. We have developed Molecules for Inactivation of Synaptic Transmission (MISTs) that can be genetically targeted to allow the reversible inactivation of neurotransmitter release. MISTs consist of modified presynaptic proteins that interfere with the synaptic vesicle cycle when crosslinked by small molecule "dimerizers." MISTs based on the vesicle proteins VAMP2/Synaptobrevin and Synaptophysin induced rapid ( approximately 10 min) and reversible block of synaptic transmission in cultured neurons and brain slices. In transgenic mice expressing MISTs selectively in Purkinje neurons, administration of dimerizer reduced learning and performance of the rotarod behavior. MISTs allow for specific, inducible, and reversible lesions in neuronal circuits and may provide treatment of disorders associated with neuronal hyperactivity.

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    Svoboda Lab
    06/01/05 | Geometric and functional organization of cortical circuits.
    Shepherd GM, Stepanyants A, Bureau I, Chklovskii D, Svoboda K
    Nature Neuroscience. 2005 Jun;8(6):782-90. doi: 10.1016/j.tins.2005.05.006

    Can neuronal morphology predict functional synaptic circuits? In the rat barrel cortex, ’barrels’ and ’septa’ delineate an orderly matrix of cortical columns. Using quantitative laser scanning photostimulation we measured the strength of excitatory projections from layer 4 (L4) and L5A to L2/3 pyramidal cells in barrel- and septum-related columns. From morphological reconstructions of excitatory neurons we computed the geometric circuit predicted by axodendritic overlap. Within most individual projections, functional inputs were predicted by geometry and a single scale factor, the synaptic strength per potential synapse. This factor, however, varied between projections and, in one case, even within a projection, up to 20-fold. Relationships between geometric overlap and synaptic strength thus depend on the laminar and columnar locations of both the pre- and postsynaptic neurons, even for neurons of the same type. A large plasticity potential appears to be incorporated into these circuits, allowing for functional ’tuning’ with fixed axonal and dendritic arbor geometry.

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