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The NEURONS and NEURAL SYSTEM: a 21st CENTURY PARADIGM This material is excerpted from the full β-version of the text. The final printed version will be more concise due to further editing and economical constraints. A Table of Contents and an index are located at the end of this paper. A few citations have yet to be defined and are indicated by “xxx.” James T. Fulton Neural Concepts [email protected] January 15, 2018 Copyright 2011 James T. Fulton [xxx clear remaining xxx’s and [figure and [section editing markes 9 Stage 3, Signal Transmission Neurons 1 9.1 Introduction [xxx may want to pick up words from old Chapter 10 about NoR. Search for 10.5 to highlight locations ] There are two distinct methods of signal transmission employed in the neural system, graded potential conduction or tonic signaling, and pulse propagation or phasic signaling. Graded potential and tonic signaling both refer to analog waveform signaling. Graded potential or tonic signaling is only employed within stages 1, 2, 4, 5 & 6 of neural signaling. Phasic (pulse) propagation is only used within stage 3 and stage 7 signaling. Propagation, as a technique, has not been discussed in the biophysical literature previously except indirectly. While the high transmission speed associated with phasic signaling (greater than 10 meters/sec) has been documented, the mechanism involved has not been elucidated. Attempts to explain axonal propagation by Lord Kelvin in the 19th Century and Rall in the 20th Century were exemplary failures (Section 9.1.1.3) . This work develops neural propagation as a mechanism based on Maxwells’ General Wave Equations (GWE). This work will use the term signal transmission in the broad sense and differentiate between signal conduction, the slow flow of electrons in the orthodromic direction, and signal propagation, the rapid movement of electrons perpendicular to the orthodromic direction as a part of the wave projection mechanism used in both cables and broadcasting. Juusola, et. al. have recently explored some aspects of graded-potential (i.e., analog) conduction along electrotonic signal paths, including electrotonic synapses2. Their figure 4C presents data on the various quiescent potentials (resting potentials) found by different investigators for both pre and post synaptic plasmas. Unfortunately, the different data points on the pre and post synaptic side are not paired. This chapter will only address pulse propagation or phasic signaling as used in the neural system. Such neurons are found primarily in mammalian animals. This chapter will address the cytology, morphology, pathology and operation of the individual stage 3 neurons. The anatomy of the stage 3 neurons of the mammal was introduced in Chapter 1 and is discussed in greater detail in Chapter 10. A critical feature of the axons of stage 3 neurons is the periodic morphological constriction of the axons. The French pathologist Louis Antoine Ranvier first described this periodic constrictions 1Released: 15 January 2018 2Juusola, M. et. al. (1996) Op. Cit. Signal Transmission 9- 3 which interrupted the enshrouding of the axon by myelin. However, its functional significance has been obscure up to the present time. It has been described many times as a morphological oddity or a mere structural component. In fact, its physiological role is critical. These constrictions are now known as Nodes of Ranvier and to be the location of phasic signal regenerators critical to the operation of stage 3 neurons. Zagoren & Fedoroff edited a volume on the Node of Ranvier in 19843. It contains some useful electron-micrographs but is otherwise largely obsolete. All of their models employ simple RC circuits in electrical configurations while relying upon the chemical neuron concepts of sodium and potassium channels. Their “Current working model of the node of Ranvier” on page 319 is barely more than two dashed lines connecting two myelinated axon segments. Page 333 does show an excellent image of a stained axon of a pyramid cell reflecting the attraction of positive charges to the outside of the axon due to the presence of the high negative charge within it. More recently, Fields introduced a paper by Tomassy et al. that reviewed the subject of stage 3 propagation based on their interpretation of the role of myelin in the cytology of the phasic neurons used therein. The Fields paper made several open ended statements of interest but included no detailed models4. “Myelin is often compared to electrical insulation on nerve fibers. However, nerve impulses are not transmitted through neuronal axons the way electrons are conducted through a copper wire, and the myelin sheath is far more than an insulator. Meylin fundamentally changes the way neural impulses (information) are generated and transmitted, and its damage causes dysfunction in many nervous systems disorders including multiple sclerosis, cerebral palsy, stroke, spinal cord injury and cognitive impairments.“ While the above quotation is true, it offers no indication of how myelin is causal in these diseases. He then goes on, “A detailed understanding of myelin structure is therefore imperative, but is lacking.” More is needed that an understanding of the structure of myelin; it is the functional role of myelin that is most critical. With an understanding of its functional role, abnormalities related to its structure expose the reasons for the diseases associated with myelin. Fields does note in closing, “Myelin ...facilitates modes of nervous system function beyond the Neuron Doctrine, . .” This chapter will describe both the functional and structural role in much greater detail than the paper by Tomassy et al. Tomassy et al5. address the gross structural details of myelin in a variety of situations but does not address the functional role of myelin directly. Nor does it address the fascinating structure of the myelin layers as they approach a specific Node of Ranvier (in order to form a functional “half- section” of electrical filter theory (Section 9.1.2.4 in this work & in greater detail in Sections 10.3.5 & 10.5.2 of “Processes in Biological Vision” (PBV)). In their discussion, they note, “. .the thickness of the myelin sheath varies greatly, and it is a major determinant of the speed of impulse propagation.” Contrary to the statement, “High resolution maps of myelin distribution along individual axons are not currently available,” the geometry of the myelin forming two half- sections on either side of a Node of Ranvier is reproduced in figure 10.5.2-9 of PBV and originally presented by Rydmark & Berthold in 19836. Tomassy et al. discussed a variety of neurons in the CNS without describing their individual functions, and thereby failing to differentiate the application of myelin in these different neuron types. They essentially treat all “pyramid” shaped neurons as equivalent, even though some are employed in the encoding of analog signals to generate action potential streams and others are used to decode action potential streams to recover analog information. Other smaller “pyramid” neurons in the CNS are actually stage4, 5 & 6 neurons handling only analog (tonic) 3Zagoren, J. & Fedoroff, S. eds. (1984) The Node of Ranvier. NY: Academic Press 4Fields, R. (2014) Myelin—More than insulation Science vol 344, pp 264-267 5Tomassy,G. Berger, D. Chen, H-H. et al. (2014) Distinct profiles of meylin distribution along single axons of pyramidal neurons in the neocortex Science vol 344, pp 319-324 6Rydmark, M. & Berthold, C. (1983) Electron microscopic serial section analysis of nodes of Ranvier in lumbar spinal roots of the cat J. Neurocytol vol. 12 pp. 475-505 and 537-565 4 Neurons & the Nervous System signals. Tomassy et al. note, “It is interesting that these three profiles of myelination can be found in neurons located in immediately adjacent positions within the same cortical layer.” They close their discussion with the assertion, “Our results suggest that different classes of pyramidal neurons are endowed with different abilities to affect OL (oligodendroctyes) distribution and myelination.” This work suggests the neuron/OL relationship is quite different. The genetic code describes the form of both the neural cell and the application of OL to that neural cell in order to achieve the desired performance. Tomassy et al. do identify premyelin axonal segments (PMAS) which are in fact portions of the neuron soma and not a separate axonal segment. These regions contain the axon hillock (the location of the Activa generating action potentials in stage 3 encoding neurons). Only the post Activa portion of the PMAS needs to be myelinated. However, if this portion is short, a Node of Ranvier may be inserted prior to the beginning of myelination on the first true axon segment. Tomassy et al. close with a very insightful, although less than specific, comment, “Although the functional significance of these heterogeneous profiles of myelination awaits future elucidation, we propose that it may have served the evolutionary expansion and diversification of the neocortex by enabling the generation of different arrays of communication mechanisms and the emergence of highly complex neuronal behaviors.” It did! The comment applies to the peripheral neural system as well as the neocortex. This chapter will address the following; Section 9.1.1, the topology of signal projection neurons, Section 9.1.2, the physiology and propagation of neural signals, Section 9.2, encoding of neural signals, Section 9.3, actual codes used for neural signals, Section 9.4, the functional role of the Node of Ranvier, Section 9.5, the synapse in signal projection, Section 9.6, the stellite neuron as a signal decoder, Section 9.7, special topics related to signal projection. 9.1.1 The fundamental topology of the stage 3 signal projection circuit While the neurons of stage 3 generating action potentials represent only a small number of the total number of neurons (about 5%), they play a major functional role and have been studied most closely (because of their ease of access and easily isolated signals).
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