Wiring up distant neurons in the brain is costly to an organism. Whether wiring cost is mainly due to wiring volume, metabolic expense, signal delay and attenuation, or developmental overhead, one thing is certain: wiring cost increases with the distance between connected neurons. Therefore, placement of connected neurons as close to each other as possible reduces wiring cost and confers evolutionary advantage to an organism. This consideration leads to a hypothesis, often referred to as the wiring economy principle, that wiring minimization plays an important role in determining brain organization.

The utility of the wiring economy principle derives from its explanatory and predictory power. Various features of brain organization, from topographic maps to dendritic and axonal arbor sizes can be explained as a result of wiring minimization for a given neuronal circuit. To do this, we specify neuronal circuits and search for optimal placements of neuronal components. For different parameters of neuronal circuits we find different optimized layouts, thus establishing a mapping between neuronal circuits and spatial layout. In addition to accounting for existing spatial layouts, we can use this mapping in the reverse direction to make predictions about neuronal circuits from the observed spatial layout. Because the spatial layout is often known while the circuit is not, the wiring economy principle is a powerful tool for uncovering brain circuits and eventually understanding brain function.

Because the wiring economy principle answers why rather than how questions, it shares strengths and weaknesses of teleological approaches. The wiring economy principle allows one to bypass developmental analysis, and, hence does not require a detailed knowledge of developmental rules. Testable predictions about the final outcome of development can be made. These predictions can help guiding future experiments. Of course, bypassing development means that the wiring economy principle in many cases cannot generate predictions regarding outcomes of various developmental manipulation. However, the wiring economy principle places important constraints on the possible form of developmental rules and should, therefore, be helpful in uncovering these rules.

As with any hypothesis, the validity of the wiring economy principle can only be affirmed by its successful application. We and others used the principle to explain features of brain organization and to make experimentally testable predictions. Experimental confirmations of these predictions should be the strongest argument in favor of the wiring economy principle.

The history of the wiring economy principle in neuroscience goes back to Cajal. Since then, many scientists have appealed to this principle as exemplified by the following quotes on wiring economy:

"After the many shapes assumed by neurons, we are now in a position to ask whether this diversity ... has been left to chance and is insignificant, or whether it is tightly regulated and provides an advantage to the organism. ... we realized that all of the various conformations of the neuron and its various components are simply morphological adaptations governed by laws of conservation for time, space, and material. [Laws of conservation is Cajal's terminology for the wiring economy principle]" S.R. y Cajal in Histology of the nervous system of man and vertebrates, p.116, Oxford University, 1995.

"I have argued that the retina is topologically mapped [onto the visual cortex] in order to keep intracortical connections short..." A. Cowey, Q. J. Exp. Psychol. 31, 1-17 (1979).

"Economizing on wire is the single most important priority for both nerves and chips." C. Mead in Analog VLSI and neural systems, p.102, Addison-Wesley, 1989.

"...maps are common because continuous maps are computationally efficient for local computations and local computations are a common feature of many sensory processing tasks." M.E. Nelson and J.M. Bower, TINS13, 403-8 (1990).

"It seems likely that there has been considerable evolutionary pressure on the brain to organize itself so that the overall volume of this connections is kept as small as possible, and indeed various features of cortical design suggest a principle of wiring economy." G. Mitchison, Proc R Soc Lond B Biol Sci  245, 151-8 (1991).

"There seems little doubt that subdividing the cortex into areas confers a considerable advantage in wiring economy..." G. Mitchison, TINS 15, 122-6 (1992).

"At multiple hierarchical levels - brain, ganglion, individual cell - physical placement of neural components appears consistent with a single , simple goal: minimize cost of connections among the components. The most dramatic instance of this "save wire" organization principle is reported for adjacencies among ganglia in the nematode nervous system; among about 40,000,000 alternative layout orderings, the actual ganglion placement in fact requires the least total connection length." C. Cherniak, Journal of Neuroscience 14, 2418 (1994).

"One example of compact wiring ... is the layout of areas across the surface of the cerebral cortex, as connections occur with high probability between adjacent areas but with low probability between distant areas." D.C. Van Essen, Nature 385, 313 (1997).

"The principle of minimizing wire length appears to be a general factor governing the connections of nervous systems." J.M. Allman in Evolving Brains, p.155, W.H. Freeman and Co., 1999.