Talk:Axonal conduction delays
Overall the article is well organized, well written, and stimulating to read. The article should be accessible to its target audience. Table 1 is especially welcome.
There are just a few criticisms, which are expanded on below. First, the current version of the article may appear a bit dry to its intended audience. To break up the text, I have suggested the inclusion of few figures to help reinforce key points. Second, I think further explanation is required regarding myelin thickness and the relationship between axon diameter and conduction velocity for unmyelinated axons. Third, a number of key statements lack an obvious citation making it difficult for the interested reader to follow up on these points. Fourth, there appears to be no mention that conduction properties change during pathway development (e.g. Foster et al 1982 Dev Brain Res 3:371). Given many experiments are conducted on immature brain slices, it would be useful for the reader to be aware that caution in needed when comparing conduction properties measured at different postnatal ages in the same species. Fifth, while understandably the vast majority of the article concerns in vivo recordings of extrinsic axonal pathways (see Table 1), there appears little mention of what happens regarding axonal delays within brain structures such as cerebral cortex.
The authors have generally been careful about their use of terminology but the novice reader may wonder whether terms such as fibre vs axon or unmyelinated vs nonmyelinated are interchangeable. Some clarification regarding terms at the start of the article would assist the reader.
Axonal conduction velocities and conduction delays
(1) The authors rightly state the presence of myelination is a main structural determinant of conduction velocity. Yet they do not mention that the number of lamellae in the myelin sheath around an axon cylinder can vary. A naïve reading of the current text might give the impression that when present myelination is the same for all axons. In a tangential nerve cross-section of primate visual cortex, for instance, the numbers of lamellae per axon can range from 2 to 36 (Peters et al 2001 J Comp Neurol 435: 241). The authors should mention the variation in sheath thickness (or number of wrappings) and its relationship to conduction velocity. In addition, the authors might mention the 'g-ratio': its wide range of values and evidence regarding its relationship to axon diameter.
(2) “Whereas the conduction velocity of myelinated axons increase in a linear manner with increasing diameter, conduction velocity of unmyelinated axons is proportional to the square root of axon diameter.” This key statement, which does not receive a citation, appears quite definite. But how strong is the empirical support for this statement? Waxman and Bennett (1972) mainly examined Rushton's predictions of local circuit theory for myelinated axons (Rushton 1951 J Physiol 115: 101), who, surprisingly, is not cited in the article. While the evidence for an approximately linear relationship between axon diameter and conduction velocity for myelinated axons is reasonably good, the empirical support for conduction velocity increasing with the square root of axon diameter for unmyelinated axons is less clear cut. A number of studies suggest exponents >0.5 for unmyelinated axons. For example, Hoffmeister et al (1991 Neuroscience 42: 603) argue their data support an approximately linear axon diameter-conduction velocity relationship for unmyelinated axons. As this study is cited by at least one of the existing references, Wang et al (2008), an interested reader following up this Scholarpedia article may well become confused by conflicting statements. The authors should clarify the situation and probably make a less definite statement regarding unmyelinated axons. It would help if the authors could provide a reason for the discrepancy between theory and experiment such as differences in specific membrane properties.
(3) A figure illustrating the empirical relationship between axon diameter and conduction velocity for myelinated and unmyelinated axons, a key structural factor in axonal conduction delays, would aid the reader's understanding.
(4) The article does not mention any alternative methods of estimating conduction velocity or latency such as membrane potential optical imaging (e.g. Antic & Zecevic 1995 J Neurosci 15:1392 and http://www.scholarpedia.org/article/Voltage-sensitive_dye).
(5) “Invertebrates, for example, do not insulate their axons with myelin, and when they require rapid impulse conduction they usually achieve this with dramatic increases in axonal diameter.” There is no citation linked with this statement.
(6) Perhaps start a new paragraph with sentence “Other structural factors...”.
Axonal conduction in the peripheral nervous system: structure-function correlations
(7) Typo: “the smallest myelinated fibers 1 – 5 um)” is missing an opening round bracket.
Axonal conduction in the central nervous system: structure-function correlations
(8) “Many central axons are short and make local connections over distances of a few hundred microns, with correspondingly short conduction delays (< 1 ms).” There is no citation associated with this wide-ranging statement.
(9) To give the reader a flavour of how conduction measurements are obtained, a figure (or movie?) to explain the antidromic activation method with actual data would be informative – perhaps showing inter-trial variability to explain how a final estimate is reached.
(10) “Notably, in these populations, axonal conduction times are related to sensory or movement-related response properties, with many of the slowest conducting axons lacking sensory or motor related responses and showing very low levels of spontaneous impulse activity. (Sirota et al., 2005; review in Swadlow, 2000).” Not sure I completely understood the meaning of this sentence. Does it mean the conduction times of axons tend to be fast when relaying sensory or movement-related signals but slow when not carrying sensory or movement-related signals?
(11) “Interestingly, the diameter spectrum of the fine unmyelinated axons is quite constant across species.” There is no citation given for this general statement.
(12) “In the corpus callosum of both monkeys and rabbits, for example, the great majority of unmyelinated axons are 0.1 – 0.3 microns in diameter (median values = 0.2 microns in both species), with a similar ratio of myelinated to nonmyelinated axons.” There is no citation given for this statement.
Conduction delays and synchrony of postsynaptic events
(13) A simple figure (or movie?) would help the reader to understand the concept of isochronicity (temporal coherence).
(14) The authors might mention that differential myelination has been proposed as a mechanism for compensating for axon length differences in isochronicity (Suigihara et al 1993; also Lang & Rosenbluth 2003 J Neurophysiol 89: 2259; Salami et al 2003 Proc Natl Acad Sci USA 100: 6174).
(15) To partly counter the absence of information on intrinsic axonal delays, the authors might mention that the branching pattern of intracortical axon arbors may be designed to ensure a tight (linear) relationship between axonal delay and cortical distance to promote temporal coherence (Budd et al 2010 PLoS Comput Biol 6(3): e1000711).
(16) Typo: “(Sherman and Guillary, 1998)” should be Guillery, as in References.
Conduction delays and disease
(17) Typo: “regions (Craner et al, 2004.” is missing a closing round bracket.
(18) Are all Table 1 values obtained from adult animals? If so, please state this table legend, though see point (19) below.
(19) The authors should consider adding at least a few additional tabular entries for intrinsic axonal delays, e.g. horizontal intracortical axons 0.3 m/s in vitro adult rat (Lohmann & Roerig 1994 J Comp Neurol 344: 543).
(20) Typo: Please add 'a' and 'b' to the consecutive Swadlow 1974 references listed and check citations in text and table are correct.