Morphologic evidence for spatially clustered spines in apical dendrites of monkey neocortical pyramidal cells

Authors

  • Aniruddha Yadav,

    1. Fishberg Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York 10029
    2. Computational Neurobiology and Imaging Center, Mount Sinai School of Medicine, New York, New York 10029
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  • Yuan Z. Gao,

    1. Fishberg Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York 10029
    2. Computational Neurobiology and Imaging Center, Mount Sinai School of Medicine, New York, New York 10029
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  • Alfredo Rodriguez,

    1. Fishberg Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York 10029
    2. Computational Neurobiology and Imaging Center, Mount Sinai School of Medicine, New York, New York 10029
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  • Dara L. Dickstein,

    1. Fishberg Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York 10029
    2. Computational Neurobiology and Imaging Center, Mount Sinai School of Medicine, New York, New York 10029
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  • Susan L. Wearne,

    1. Fishberg Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York 10029
    2. Computational Neurobiology and Imaging Center, Mount Sinai School of Medicine, New York, New York 10029
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    • We dedicate this article to Susan L. Wearne, our friend, colleague, and mentor, who passed away in September, 2009.  Grant Sponsor: National Institutes of Health; Grant numbers: MH071818, AG035071, AG025062, and AG00001.

  • Jennifer I. Luebke,

    1. Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts 02118
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  • Patrick R. Hof,

    1. Fishberg Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York 10029
    2. Computational Neurobiology and Imaging Center, Mount Sinai School of Medicine, New York, New York 10029
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  • Christina M. Weaver

    Corresponding author
    1. Computational Neurobiology and Imaging Center, Mount Sinai School of Medicine, New York, New York 10029
    2. Department of Mathematics, Franklin and Marshall College, Lancaster, Pennsylvania 17604
    • Department of Mathematics, Franklin and Marshall College, P.O. Box 3003, Lancaster, PA 17604-3003
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Abstract

The general organization of neocortical connectivity in rhesus monkey is relatively well understood. However, mounting evidence points to an organizing principle that involves clustered synapses at the level of individual dendrites. Several synaptic plasticity studies have reported cooperative interaction between neighboring synapses on a given dendritic branch, which may potentially induce synapse clusters. Additionally, theoretical models have predicted that such cooperativity is advantageous, in that it greatly enhances a neuron's computational repertoire. However, largely because of the lack of sufficient morphologic data, the existence of clustered synapses in neurons on a global scale has never been established. The majority of excitatory synapses are found within dendritic spines. In this study, we demonstrate that spine clusters do exist on pyramidal neurons by analyzing the three-dimensional locations of ∼40,000 spines on 280 apical dendritic branches in layer III of the rhesus monkey prefrontal cortex. By using clustering algorithms and Monte Carlo simulations, we quantify the probability that the observed extent of clustering does not occur randomly. This provides a measure that tests for spine clustering on a global scale, whenever high-resolution morphologic data are available. Here we demonstrate that spine clusters occur significantly more frequently than expected by pure chance and that spine clustering is concentrated in apical terminal branches. These findings indicate that spine clustering is driven by systematic biological processes. We also found that mushroom-shaped and stubby spines are predominant in clusters on dendritic segments that display prolific clustering, independently supporting a causal link between spine morphology and synaptic clustering. J. Comp. Neurol. 520:2888–2902, 2012. © 2012 Wiley Periodicals Inc.

Ancillary