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Kozorovitskiy, Yevgenia

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Kozorovitskiy

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Yevgenia

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Kozorovitskiy, Yevgenia

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20122

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Author's Publications: search.filters.isAuthorOfPublication.5dc44b06-6810-45cb-8898-3f2a27dbe924

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    Cortical synaptogenesis and excitatory synapse number are determined via a Neuroligin-1-dependent intercellular competition
    (2012) Kwon, Hyung-Bae; Kozorovitskiy, Yevgenia; Oh, Won-Jong; Peixoto, Rui T.; Akhtar, Nazia; Saulnier, Jessica L.; Gu, Chenghua; Sabatini, Bernardo
    Members of the neuroligin (NL) family of cell-adhesion proteins are found at excitatory and inhibitory synapses and are mutated in some familial forms of autism spectrum disorders. Although they display synaptogenic properties in heterologous systems, a function of NLs in vivo in regulating synapse formation and synapse number has been difficult to establish. Here we show that neuroligin-1 (NL1), which is located at excitatory post-synaptic densities, does regulate activity-dependent synaptogenesis as well as mature synapse number on cortical layer 2/3 pyramidal neurons in vivo. However, synapse number is not sensitive to absolute NL1 levels but rather to transcellular differences in the relative amounts of NL1. These effects are independent of the cell-autonomous regulation of NMDA-type glutamate receptors by absolute levels of NL1. Our data indicate that transcellular competitive processes govern synapse formation and number in developing cortex and that NL1 plays a central function in these processes.
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    Recurrent network activity drives striatal synaptogenesis
    (2012) Kozorovitskiy, Yevgenia; Saunders, Arpiar; Johnson, Caroline; Lowell, Bradford; Sabatini, Bernardo
    Neural activity during development critically shapes postnatal wiring of the mammalian brain. This is best illustrated by the sensory systems, in which the patterned feed-forward excitation provided by sensory organs and experience drives the formation of mature topographic circuits capable of extracting specific features of sensory stimuli1,2. In contrast, little is known about the role of early activity in the development of the basal ganglia, a phylogenetically ancient group of nuclei fundamentally important for complex motor action and reward-based learning3,4. These nuclei lack direct sensory input and are only loosely topographically organized5,6, forming interlocking feed-forward and feed-back inhibitory circuits without laminar structure. Here we use transgenic mice and viral gene transfer methods to modulate neurotransmitter release and neuronal activity in vivo in the developing striatum. We find that the balance of activity among the two inhibitory and antagonist pathways in the striatum regulates excitatory innervation of the basal ganglia during development. These effects indicate that the propagation of activity through a multi-stage network regulates the wiring of the basal ganglia, revealing an important role of positive feedback in driving network maturation.