, 2013). Size-invariant time parsing in neural networks strongly depends on neuronal conduction velocity. As an example, for gamma oscillation to be synchronous in both hemispheres of the mouse brain, at an interhemispheric distance of ∼5–10 mm, a conduction velocity of 5 m/s is sufficient (Buzsáki et al., 2003). Maintaining coherent oscillations at the same frequency in the human brain, with a 70–140 mm interhemispheric distance (Varela et al., 2001), requires much find more more

rapidly conducting axons. Of the various structural-anatomical possibilities, evolutionary adaptation of axon size and myelination appear to be most critical for a brain-size-invariant scaling of network oscillations because they both determine the conduction velocity of neurons. The benefits of increased brain size should therefore be offset by the cost of larger-caliber axons (Figure 3; Aboitiz et al., 2003 and Wang et al., 2008) so that signals can travel longer distances within approximately the same time window. The scaling laws of axons support this hypothesis. Indeed, axon calibers in the brain vary by several orders of magnitude (Swadlow, 2000). An important evolutionary strategy is the myelination of axons and saltatory conduction; the speed of conduction along a myelinated axon scales relatively linearly with axon diameter (Hursh, 1939 and Tasaki, 1939). In humans, the

great majority of callosal axons, which connect approximately 2%–3% of cortical neurons, have diameters <0.8 μm, but the thickest 0.1% of axons can exceed 10 μm in diameter (Aboitiz http://www.selleckchem.com/products/PLX-4720.html et al., 2003). The calibers of axons emanating from the same neurons but targeting different brain regions can vary

substantially, exemplifying a complex system of lines of communication with different geometrical and time-computing properties (Innocenti et al., 2013). However, a proportional increase of PI-1840 axon caliber in larger brains would enormously increase brain size. Instead, a minority of axons with a disproportionally increased diameter might be responsible for keeping the timing relatively constant across species. Indeed, it is the thickest diameter tail of the distribution that scales best with brain size (Figure 3), whereas across species the fraction of thinner fibers/total numbers of cortical neurons decreases (Swadlow, 2000, Wang et al., 2008, Olivares et al., 2001 and Aboitiz et al., 2003). Although adding a small fraction of giant axons to the neuropil still demands increased volume and an increasing share of the white matter in larger brains, the metabolic costs and the needed volume are still orders of magnitude less than would result from the proportional increase of axon calibers of all neurons. Adding a very small fraction of very-large-diameter axons might guarantee that the cross-brain conduction times increase only modestly (Figure 3B) across species (Wang et al., 2008). The host neurons of the giant axons still need to be identified.