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Researchers uncover scaffolds in the brain's wiring diagram

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  • Robert Karl Stonjek
    Public release date: 28-Feb-2005 Contact: Peter Sherwood sherwood@cshl.edu 516-367-6947 Cold Spring Harbor Laboratory Researchers uncover scaffolds in the
    Message 1 of 1 , Mar 1, 2005
      Public release date: 28-Feb-2005
      Contact: Peter Sherwood
      Cold Spring Harbor Laboratory

      Researchers uncover scaffolds in the brain's wiring diagram

      Many implications seen for biomedical research

      The human brain is estimated to contain 100 billion neurons (the
      number 1 followed by eleven zeros). Because a typical neuron
      forms ~1,000 synaptic connections to other neurons, the total
      number of synapses in the brain is estimated to be 100 trillion
      (the number 1 followed by 14 zeros). The thin projections from
      neurons that form connections with each other (axons and
      dendrites) can be thought of as the biological "wiring" of the

      Neuroscientists already know that brain neurons can and do form
      specific rather than random connections with each other to
      generate the observed wiring diagram of the brain. However, the
      precise patterns of such non-random connections, how the
      patterns are formed, and how these patterns underlie the brain's
      extraordinary information processing capacity are important
      questions that Cold Spring Harbor Laboratory theoretical
      neuroscientist Dmitri Chklovskii is exploring. An article
      published in this week's issue of PLoS Biology (March 1, 2005)
      describes Chklovskii's discovery of strongly preferred patterns
      of connectivity or scaffolds within the wiring diagram of the
      rat brain. The patterns are likely to correspond to modules that
      play an important role in brain function not only in rats, but
      also in humans.

      Chklovskii and his colleagues use statistical analysis and
      mathematical modeling--coupled with in vivo, experimental
      observations--to search for recurrent, non-random patterns of
      local connectivity within the vast thickets of brain wiring
      diagrams. Finding such patterns would be strong evidence for the
      presence of functional modules (for example, "local cortical
      circuits") that process information. The researchers recently
      uncovered evidence of such functional modules by using two
      complementary approaches.

      In the first study--published in December--they chose the
      nematode worm C. elegans as a relatively simple model system.
      Studies by others had determined that this organism has 302
      neurons, and had mapped which neurons connect with which.
      However, those studies did not characterize non-random patterns
      of connectivity in a rigorous way.

      When Chklovskii and his colleagues considered all 13 possible
      patterns of connectivity that can occur among three neurons (one
      such "triplet" pattern being "neuron A connects to B, B connects
      to C, and A connects to C"), they found that three particular
      patterns, including the aforementioned one, stood out as
      appearing far more frequently in the C. elegans wiring diagram
      than they would by chance. They also discovered that some
      triplet patterns were less common than predicted by chance.
      Taking the analysis a step further, Chklovskii found that among
      all 199 possible patterns of connectivity that can occur among
      four neurons, one particular pattern stood out in C. elegans as
      appearing more frequently than it would by chance.

      Significantly, Chklovskii considered whether the frequent
      connectivity patterns or "motifs" they discovered might be
      accounted for by previously known principles of neurobiology.
      They found no such explanation for the existence of the motifs,
      indicating that further analysis of the motifs may reveal
      important information about nervous system structure and

      Because it was based purely on anatomical data collected by
      electron microscopy, Chklovskii's C. elegans study did not
      include telling information about the strengths of connections
      between neurons. Therefore, to extend his findings into the
      physiological realm, Chklovskii collaborated with researchers at
      Brandeis University on the study published this week in PLoS
      Biology. The Brandeis group had previously collected one of the
      largest electrophysiological data sets of its kind ever
      recorded: measurements of the connectivity of some 3,000
      individual neurons in the rat visual cortex.

      Chklovskii realized that the Brandeis data could be used to
      explore his ideas concerning functional modules in the brain. He
      and his colleagues detected some of the very same non-random
      patterns of connectivity in the rat brain as they had observed
      in C. elegans. More importantly, they found that most
      connections formed by neurons in the rat visual cortex are weak,
      and that the stronger connections (~17% of all connections)
      account for as much as half of the total synaptic strength of a
      particular network. In part because more strongly connected
      neurons fire more reproducibly, Chklovskii proposes that strong
      cortical synapses--with particular connectivities--act as a
      network "scaffold" that is likely to generate reproducible
      patterns of activity and play an important role in brain
      function. "Local brain circuits can therefore be viewed as a
      'skeleton' of strong connections in a sea of weaker ones," says


      Ian Pitchford PhD CBiol MIBiol
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