One of the earliest neuroscientists, Santiago Ramón y Cajal, postulated that brains are arranged to minimise wire length [1]. In [1] Dmitri Chklovskii and Charles Stevens formulate this problem as follows:

Wiring a brain presents formidable problems because of the extremely large number of connections: a microliter of cortex contains approximately 105 neurons, 109 synapses, and 4 km ofaxons, with 60% of the cortical volume being taken up with "wire", half of this by axons and the other half by dendrites. [ 1] Each cortical neighborhood must have exactly the right balance of components; if too many cell bodies were present in a particular mm cube, for example, insufficient space would remain for the axons, dendrites and synapses. Here we ask "What fraction of the cortical volume should be wires (axons + dendrites)?"

While the formulation of this problem continues to evolve and its solution is far from settled, I am motivated by its potential impact on different areas of neuroscience. In particular, the areas of developmental neuroscience, network neuroscience and biophysics(i.e. the energetic constraints on information processing in human brains).

Due to its historical importance and potential impact on the field of neuroscience, I'd like to learn more about the state-of-the-art on this problem. From my own literature review and a question I asked on Twitter, I managed to gather the following references listed below.

In this context, are there essential post-2000 publications that aren't in this reference list? One thing I find curious is that although there has been an explosion of neuroscience data since the year 2010 nearly half the papers I have found that directly attempt to answer the question were written before 2010.


  1. D. Chklovskii, C. Stevens. Wiring optimization in the brain. NIPS. 2000.
  2. D. Van Essen. A tension-based theory of morphogenesis and compact wiring in the nervous system. Nature. 1997.
  3. G. Shepherd, A. Stepanyants, I. Bureau, D. Chklovskii and K. Svoboda. Geometric and functional organization of cortical circuits. Nature Neuroscience. 2005.
  4. M. Kaiser & C. Hilgetag. Nonoptimal Component Placement, but Short Processing Paths, due to Long-Distance Projections in Neural Systems. PLOS. 2006.
  5. A. Stepanyants, L. Martinez, A. Ferecskó , and Z. Kisvárda. The fractions of short- and long-range connections in the visual cortex. PNAS. 2008.
  6. Q. Wena, A. Stepanyants, G. Elstonc, A. Grosberg, and D. Chklovskii. Maximization of the connectivity repertoire as a statistical principle governing the shapes of dendritic arbors. PNAS. 2009.
  7. C. Cherniak. Neural Wiring Optimization. 2011.
  8. E. Bullmore , O. Sporns.The economy of brain network organization. Nat Rev Neurosci. 2012.
  9. M. Hofman. Evolution of the human brain: when bigger is better. Frontiers in Neuroanatomy. 2014.
  10. A. Gushchin, A. Tang. Total Wiring Length Minimization of C. elegans Neural Network: A Constrained Optimization Approach. PLOS. 2015.
  11. J. Niven. Neuronal energy consumption: biophysics, efficiency and evolution. 2016.
  12. I. Wang & T.Clandinin. The Influence of Wiring Economy on Nervous System Evolution. Current Biology. 2016.
  13. S. Srinivasan, C. Stevens. Scaling principles of distributed circuits. biorxiv. 2018.
  14. J. Stiso & D. Bassett. Spatial Embedding Imposes Constraints on the Network Architectures. Arxiv. 2018. of Neural Systems
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    $\begingroup$ Though this is outside my sub-specialty I don't think you are likely to find a principal authoritative review, since neuroscience is typically too decentralized for such a thing to make sense and you're talking about quite a broad topic. Seems like you have a decent reference list to start with, from there I'd do some searches for "cited by" relative to the references you find closest to your interest. You also might search for "small worldedness" $\endgroup$
    – Bryan Krause
    May 10, 2019 at 15:29


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