What is the functional significance of such isochronicity of action potential conduction? The issue of isochronicity has actually a long history and has been demonstrated also in invertebrates. Among the oldest of these examples are the classical studies on the squid giant axons. Conduction time of the giant axons between the stellate ganglia and the mantle musculature is such that activation of the whole mantle takes place synchronously, allowing effective escape to occur. This is achieved by faster CV for longer axons, by changing axon diameters (Young, 1939
) exclusively. That is because invertebrates do not have myelination with which the CV could be enormously (~100 times) increased. In other words, vertebrates are endowed with an additional mechanism in regulating CV. It appears quite reasonable to think that vertebrates would exploit these strategies independently. In electric organs of a certain kind of fish, synchronous activation of electrocytes to produce larger electrical potentials is attained by two mechanisms; first, same as squid axon, faster CV for longer pathways, and secondly, longer circuitous route for cells closer to the target (Bennett, 1970
). The avian auditory system is another similar example where circuitous routes are used to compensate for shorter distance. The conduction time between the cochlear nucleus and its ipsi- and contralateral nucleus laminaris is matched by lengthening the path to the ipsilateral nucleus, to create a delay line for detecting the differential timing of sound inputs to both ears for sound localization. In these cases, the advantage of the isochronous conduction is obvious.
By analogy, in those connections we have discussed above, such as olivocerebellar, amygdalo-perirhinal, and corticofugal from ventral temporal cortex, isochronous activations of target cells should have clear temporal advantages. However, at this point, how isochronicity is advantageous does not seem obvious in these systems. One interesting view is that the olivocerebellar system serves as an intrinsic timing device that is essential for motor co-ordination (Llinas, 1988
). This view is based on the observation that neurons in the inferior olive are connected by gap junctions and thus exhibit oscillatory activity. This is supposed to propagate to a wide territory of the cerebellar cortex, a process for which isochronicity is essential.
A similar situation might apply to the thalamocortical pathway. Thalamic cells also show oscillatory activities intrinsically (Contreras et al., 1996
) that could cause synchronization in the functionally related target cortical cells. Isochronous or synchronous activation of group of cells distributed in distant cortical locations with zero phase-lag have been shown in visual cortex (Gray et al., 1989
), and callosally connected areas (Engel et al., 1991
). These findings attracted attention as relevant to the problem of connecting features responsible for object recognition in the spatially fractured nature of sensory representation over the cortical mantle (Llinas et al., 2002
; Singer, 1999
) and providing the perception of unity (von der Malsburg and Buhmann, 1992
). For such binding to work correctly, isochronous activation of related cells in the global cortical area would be a necessary condition. Isochronous activation of thalamocortical as well as transcallosal connections provides a physiological and anatomical explanation for these observations. Synchronous activities may also be appropriate for producing synfire chains (Abeles, 1991
). Another possible explanation for the resultant isochronicity might be, as we discussed before, that each connection has its own characteristic conduction time for information to be correctly processed in the network. Under such conditions, if postsynaptic target neurons are widely distributed, isochronous conduction will result. This is in some sense consistent with isochronicity in the developing brain as we described earlier. During development, once a pathway with a characteristic conduction time becomes functional, the specific conduction time presumably needs to be kept constant in spite of the increasing distances subsequent to growth of the body. The corpus callosum displays a significant variety in terms of myelination (Aboitiz et al., 1992
). In rats, the fraction of myelinated fibers is zeroe at birth, then it gradually increases to 53% at 300
days post-conception (Seggie and Berry, 1972
). Similarly in humans, none of the callosal fibers are myelinated at birth, and in adults 30% of the fibers remain unmyelinated. In addition, analyses of fiber composition revealed a wide variety of fiber diameters and extent of myelination depending on the target area. Callosal regions connecting prefrontal and temporoparietal association areas consist of small caliber with low myelinated fibers, whereas regions connecting primary and secondary sensorimotor areas include highly myelinated, large-caliber fibers (Aboitiz et al., 2003
). Consequently, the conduction time between two hemispheres varies from 30
ms via myelinated axons to as long as 300
ms via unmyelinated ones (Fields, 2008
). Since callosal fibers connect a variety of cortical regions with various functions, conduction times for each functions are likely to be diverse. The extent of myelination, as well as axon diameter might help regulate the conduction time to its optimal value for communicating between hemispheres. This leads to another interesting question; namely, how the conduction time of each pathway is determined in the network. Overall, our understanding regarding the time devoted to each step in neural processing is still, unfortunately, severely limited.