The nerve impulse in the axon — a new theory

The Classical Theory of function in the nervous system postulates that the nerve impulse is the result of a sequential reversal of the membrane potential due to an increased permeability of the membrane, first to sodium ions, then to potassium ions. The new theory presents a bio-physical model which depicts the nerve impulse as an event involving the motions of electrons and waves, and their interactions with sodium and potassium atoms and ions. The velocity of the nerve impulse (the most important parameter of nerve function) is determined by the product of two constants: c = the speed of light, which is a constant for all nerves; k =a constant for each nerve and is believed to be a specific property of nerve matter related in some way to the atomic process. The theory proposes that the nerve impulse in the axon is dualistic in nature (particles and waves play equally significant roles). The dualistic nature accounts for the three most fundamental characteristics of conduction of the nerve impulse: periodicity (conduction of a nerve impulse over long distances with constant velocity and form); non-summing (two nerve impulses cannot be in the same place at the same time); quantum nature of each nerve impulse — i.e., the unit message of the nerve impulse is an indivisible unit.     

Is astrocyte laminin involved in axon guidance in the mammalian CNS?

This paper provides evidence for the expression of laminin on glia in correlation with axon elongation and nerve pathway formation during embryonic development of the mouse optic nerve and other parts of the central nervous system (CNS). We show that punctate deposits of laminin on immature glial cells precede the entrance of the first optic axons into the nerve, and remain in close association with growing axons. Furthermore, we show that in one particular region of the optic pathway that the retinal ganglion cell axons avoid in normal animals (i.e., the pigmented area of the distal nerve) the punctate laminin matrix is missing. As the optic nerve matures punctate laminin deposits disappear, and laminin is reduced in the astroglial cytoplasm. The close correlation of the punctate form of laminin with early axonal growth is true not only in the optic nerve but also in some other parts of the CNS. We demonstrate such punctate laminin deposits in a model of astrocyte-induced regeneration of the corpus callosum in acallosal mice (G. Smith, R. Miller, and J. Silver, 1986, J. Comp. Neurol. 251, 23-43), and in glia associated with several normal developing axon trajectories, such as the corpus callosum, fornix, and pathways in the embryonic hindbrain. In all of these regions punctate laminin deposits are found on astroglia that are associated with early growing axons. Our results indicate that the punctate form of laminin, produced by astrocytes, may be an important factor involved in axon elongation and nerve pathway formation in the mammalian CNS.     

The sinoatrial ring bundle: a cardiac neural communication system?

The sinoatrial ring bundle (SARB), was originally described as a "whitish bundle of tissue which describes an almost complete loop around the two venae cavae and the coronary sinus" in the adult rabbit heart (Paes de Carvalho et al., 1959). The histologically and electrophysiologically differentiated structure, derived from the embryonic venous valves, was suitably placed for rapid conduction from sinoatrial (SA) to atrioventricular (AV) node, but no evidence was found for this role. Today, the function of the SARB remains obscure. Cholinesterase/silver staining reveals the neural pattern associated with the SARB and suggests a function. Throughout its extent, the SARB contains a bundle of parallel muscle fibers and accompanying long nerves. The nerves distribute to structures at either side of the loop: superolaterally to pectinate muscle and inferomedially to the region of the AV node. Along the curve of the right SARB, the nerves contribute to a dense neural plexus with nerves coiled around muscle. The plexus communicates with the nearby SA node and with the ganglia inferior to the node near the inferior vena cava. The morphological pattern of neural elements is suitably organized to suggest tension monitoring and internodal, neural communication.     

Does a cytoplasmic bridge connect the CNS axon with the inner loop of myelin?

Sarah Luse (1959) reported over 30 years ago on the presence of a bridge connecting the axon to the myelin sheath in the central nervous system (CNS). This notion has not been accepted in the literature. Wolman (1992) found that the progress of demyelination in some viral diseases affecting the CNS fits the concept of Luse, as the process occurred primarily along the major dense line of myelin, which is in continuity with the cytoplasm of the oligodendroglial cell. Injection of Lucifer yellow (LY) and horseradish peroxidase (HRP) into the vitreous of guinea pigs, with and without iontophoresis, resulted in labeling of the nerve axons and myelin. Labeling of myelin by HRP occurred along the major dense line which indicated that a transient or permanent cytoplasmic bridge connects axons and myelin in the optic nerve.     

Is progesterone a pre-hormone in the CNS?

In this paper, experimental evidences have been presented indicating that progesterone per se appears to be a powerful modulatory steroid of presynaptic striatal dopaminergic terminals of the central nervous system of the rat. This effect of the progesterone signal is concentration as well as infusion mode dependent. Low pulsatile doses of the steroid positively modulate the mechanism by which dopamine terminals respond to amphetamine stimulation and increase tissue dopamine concentration. Whereas, continuous and/or high doses of this steroid negatively modulate the response of the dopamine terminals to amphetamine stimulation and decreases tissue dopamine concentration. This effects occurs through a membrane mediated mechanism either upon the dopamine neuron directly and/or upon an interneuron. Pregnanolone a 5- beta-3 beta-metabolite of progesterone known to activate the hypothalamic LHRH neural apparatus at the level of the hypothalamus of ovariectomized estrogen primed rats in both in vitro as well as in vivo preparations was completely ineffective at the level of the corpus striatum of similar animal preparations. Therefore, it is reasonable to assume that site specific mechanisms exist within the central nervous system which may control differentially the final action of progesterone. In the hypothalamus, pregnanolone appears to be the final signal for its action on the LHRH neural apparatus, whereas in the corpus striatum, the steroid per se, and dependent on the modality and/or the strength of the signal can either directly or indirectly up-regulate (stimulatory component) or down-regulate (inhibitory component) the activity of striatal dopaminergic terminals.     

Information processing in the CNS: a supramolecular chemistry?

How does central nervous system process information? Current theories are based on two tenets: (a) information is transmitted by action potentials, the language by which neurons communicate with each other—and (b) homogeneous neuronal assemblies of cortical circuits operate on these neuronal messages where the operations are characterized by the intrinsic connectivity among neuronal populations. In this view, the size and time course of any spike is stereotypic and the information is restricted to the temporal sequence of the spikes; namely, the “neural code”. However, an increasing amount of novel data point towards an alternative hypothesis: (a) the role of neural code in information processing is overemphasized. Instead of simply passing messages, action potentials play a role in dynamic coordination at multiple spatial and temporal scales, establishing network interactions across several levels of a hierarchical modular architecture, modulating and regulating the propagation of neuronal messages. (b) Information is processed at all levels of neuronal infrastructure from macromolecules to population dynamics. For example, intra-neuronal (changes in protein conformation, concentration and synthesis) and extra-neuronal factors (extracellular proteolysis, substrate patterning, myelin plasticity, microbes, metabolic status) can have a profound effect on neuronal computations. This means molecular message passing may have cognitive connotations. This essay introduces the concept of “supramolecular chemistry”, involving the storage of information at the molecular level and its retrieval, transfer and processing at the supramolecular level, through transitory non-covalent molecular processes that are self-organized, self-assembled and dynamic. Finally, we note that the cortex comprises extremely heterogeneous cells, with distinct regional variations, macromolecular assembly, receptor repertoire and intrinsic microcircuitry. This suggests that every neuron (or group of neurons) embodies different molecular information that hands an operational effect on neuronal computation.     

The root microbiota—a fingerprint in the soil?

Background

The root system of a plant is known to host a wide diversity of microbes that can be essential or detrimental to the plant. Microbial ecologists have long struggled to understand what factors structure the composition of these communities. An overlooked part of the microbial community succession in root systems has been the potential for individual variation among plants shaped by early colonisation events such as microbial exposure of the seed inside the parent plant and during dispersal.

Scope

In this review we outline life events of the plant that can affect the composition of its root microbiota and relate ecological theory of community assembly to the formation of the root microbiota.

Conclusion

All plants are exposed to environmental conditions and events throughout their lifetime that shape their phenotype. The microbial community associated with the plant is ultimately an extension of this phenotype. Therefore, only by following a plant from its origin inside the flower to senescence, can we fully understand how the associated microbial community was assembled and what determined its composition.     

Can the immune system be harnessed to repair the CNS?

Experimental and clinical data have demonstrated that activating the immune system in the CNS can be destructive. However, other studies have shown that enhancing an immune response can be therapeutic, and several clinical trials have been initiated with the aim of boosting immune responses in the CNS of individuals with spinal cord injury, multiple sclerosis and Alzheimer's disease. Here, we evaluate the controversies in the field and discuss the remaining scientific challenges that are associated with enhancing immune function in the CNS to treat neurological diseases.     

The phylogenetic system of primates—character evolution in the light of a consolidated tree

Molecular analyses of the last decades helped solving the major open questions on the external and internal phylogenetic relationships of primates. The present review uses these data for the inference of character evolution along the branches of the primate tree. Altogether, more than 200 evolutionary changes in hard and soft tissue anatomy/morphology, behavior, physiology, and protein constitution are presented in the context of their functional relevance and adaptive value. The compilation focuses on primates as a whole and on the higher-ranked primate subtaxa with living representatives: Strepsirhini: Lorisiformes, Galagidae, Lorisidae, Lemuriformes; Haplorhini: Tarsioidea, Anthropoidea, Platyrrhini, Atelidae + Cebidae, Atelidae, Cebidae, Aotinae, Callithrichinae, Cebinae, Pitheciidae, Pithecinae, Catarrhini, Cercopithecoidea, Cercopithecinae, Colobinae, Colobini, and Hominoidea. Within Hominoidea character evolution is traced down to more peripheral branches: Hylobatidae, Hominidae, Pongo, Homininae, Gorilla, Pan + Homo, Pan, and modern humans. Character states in extinct representatives of Plesiadapiformes, Omomyoidea, Propliopithecidae, Hominini, etc. are always taken into account; they are presented in detail whenever character-state distribution in living species is ambiguous or misleading. The taxonomic sample and the characters included combine to a phylogenetic system that illustrates primate evolution and diversity. The data presented additionally provide a detailed picture of the evolutionary steps and trends involved in hominization. Reflections on the frequently underestimated role of polymorphisms in phylogenetic analyses complete the survey.     

It is all about the support — The role of the extracellular matrix in regenerating axon guidance

Although it is known for long time that the peripheral nervous system has the capacity for self-regeneration, the molecular mechanisms by which Schwann cells and extracellular matrix (ECM) guide the injured axons to regrow along their original path, remains a poorly understood process. Due to the importance of ECM molecules during development, constitutive mutant organisms display increased lethality, therefore, conditional or inducible strategies have been used to increase the survival of the organisms and allow the study of the role of ECM proteins. In a recent report published in Neuron, Isaacman-Beck and colleagues (2015) used these pioneering genetic studies on zebrafish combined with in vivo fluorescent imaging, to investigate the micro-environmental conditions required for targeted regeneration of the dorsal motor nerve of zebrafish larvae after laser-transection. A candidate gene approach targeting lh3 basal laminar collagen substrates revealed that the lh3 substrate col4α5 regulates dorsal nerve regeneration by destabilizing misdirected axons. Col4α5 was upregulated in a small population of lh3 expressing Schwann cells located ventrally and ventro-laterally to the injury site and found to co-localize with the molecule slit guidance ligand 1 (slit1a). Capitalizing on the crucial observations of mistargeted regeneration of dorsal nerves in mutant larvae, they put forward a model in which Schwann cells shape an environment that allows and directs axonal regeneration to their original synaptic target. In the light of Isaacman-Beck and colleagues (2015) findings, we will review how their study contributes to the research field, and comment on its potential implications for promoting nerve regeneration after injury.     

The natriuretic peptide system in eels: a key endocrine system for euryhalinity?

The natriuretic peptide system of a euryhaline teleost, the Japanese eel (Anguilla japonica), consists of three types of hormones [atrial natriuretic peptide (ANP), ventricular natriuretic peptide (VNP), and C-type natriuretic peptide (CNP)] and four types of receptors [natriuretic peptide receptors (NPR)-A, -B, -C, and -D]. Although ANP is recognized as a volume-regulating hormone that extrudes both Na(+) and water in mammals, ANP more specifically extrudes Na(+) in eels. Accumulating evidence shows that ANP is secreted in response to hypernatremia and acts to inhibit the uptake and to stimulate the excretion of Na(+) but not water, thereby promoting seawater (SW) adaptation. In fact, ANP is secreted immediately after transfer of eels to SW and ameliorates sudden increases in plasma Na(+) concentration through inhibition of drinking and intestinal absorption of NaCl. ANP also stimulates the secretion of cortisol, a long-acting hormone for SW adaptation, whereas ANP itself disappears quickly from the circulation. Thus ANP is a primary hormone responsible for the initial phase of SW adaptation. By contrast, CNP appears to be a hormone involved in freshwater (FW) adaptation. Recent data show that the gene expression of CNP and its specific receptor, NPR-B, is much enhanced in FW eels. In fact, CNP infusion increases (22)Na uptake from the environment in FW eels. These results show that ANP and CNP, despite high sequence identity, have opposite effects on salinity adaptation in eels. This difference apparently originates from the difference in their specific receptors, ANP for NPR-A and CNP for NPR-B. VNP may compensate the effects of ANP and CNP for adaptation to respective media, because it has high affinity to both receptors. On the basis of these data, the authors suggest that the natriuretic peptide system is a key endocrine system that allows this euryhaline fish to adapt to diverse osmotic environments, particularly in the initial phase of adaptation.     

The adipose-tissue renin-angiotensin-aldosterone system: role in the metabolic syndrome?

Overfeeding of rodents leads to increased local formation of angiotensin II due to increased secretion of angiotensinogen from adipocytes. Whereas angiotensin II promotes adipocyte growth and preadipocyte recruitment, increased secretion of angiotensinogen from adipocytes also directly contributes to the close relationship between adipose-tissue mass and blood pressure in mice. In contrast, angiotensin II acts as an antiadipogenic substance in human adipose tissue, and the total increase in adipose-tissue mass may be more important in determining human plasma angiotensinogen levels than changes within the single adipocyte. However, as increased local formation of angiotensin II in adipose tissue may be increased especially in obese hypertensive subjects, a contribution of the adipose-tissue renin-angiotensin system to the development of insulin resistance and hypertension is conceivable in humans, but not yet proven. Insulin resistance may be aggravated by the inhibition of preadipocyte recruitment, which results in the redistribution of triglycerides to the liver and skeletal muscle, and blood pressure may be influenced by local formation of angiotensin II in perivascular adipose tissue. Thus, although the mechanisms are still speculative, the beneficial effects of ACE-inhibition and angiotensin-receptor blockade on the development of type 2 diabetes in large clinical trials suggest a pathophysiological role of the adipose-tissue renin-angiotensin system in the metabolic syndrome.     

Citrate,Beneficial or Deleterious in the CNS?

Cerebellar granule neurons were incubated with or without glucose (3 mM) in the presence or absence of citrate (20 mM) using normoxic and/or hypoxic incubation conditions. During 4 h of hypoglycemia and also during hypoxia plus hypoglycemia, citrate increased lactate dehydrogenase (LDH) leakage from the cells and decreased mitochondrial activity, the latter was also the case in the presence of glucose. After 24 h of hypoglycemia, however, citrate decreased LDH leakage slightly, possibly due to its metabolism in the tricarboxylic acid cycle under these conditions. It should be noted that during mild hypoxia plus hypoglycemia a reduced LDH leakage was observed when compared to hypoglycemia alone. The 4 h low oxygen period did protect the neurons also during the 20 h re-oxygenation period. The present study might indicate that incubation of brain cell cultures in an atmosphere of air (30% oxygen) and 5% CO₂, which is used in most laboratories, can be toxic and that oxygen concentration should be lowered considerably to mimic conditions in the brain.     

Floral scent in dioeciousSalix (Salicaceae)—a cue determining the pollination system?

Floral scents of male and female inflorescences of three dioeciousSalix species were collected by head-space adsorption, and analysed by GC-MS. InSalix caprea andS. cinerea 1,4-dimethoxy benzene was the main compound, and male and female scents showed a high degree of resemblance. No dominant compound was found inS. repens and malefemale scent similarity was low. Floral scent inSalix is likely a strong orientation cue, guiding pollinators between male and female plants ensuring pollen transfer and pollination. We suggest that a high degree of male-female floral scent resemblance is coupled to a high degree of insect pollination. Floral scent does not promote reproductive isolation betweenS. caprea andS. cinerea.     

Synthesis of life in the lab? Defining a protoliving system

The synthesis of a living system in the lab has been judged by a number of critics as partly attained by the proteinoid microsphere because of its primitive properties of metabolism, growth, and reproduction. These same critics, however, judge the organism as not alive, or as being 50 to 75 percent alive (Baltscheffsky and Jurka, 1984), owing to the absence of a nucleic acid genetic coding mechanism. The experiments in retracing evolution suggest, however, that the self-sequencing of amino acids was the evolutionary precursor of modern nucleic acid templating; the genetic memory is the molecule. The proteinoid microsphere is not a modern living system, but does represent at least a protoliving system (Fox and Dose, 1972). Berra (1990, p. 75) has commented on other difficulties in defining a protoliving system. In Berra's opinion, metabolism, reproduction, responsiveness to stimuli, and cellularity constitute or describe aliveness. These properties characterize proteinoid microspheres. A number of experiments demonstrate that amino acids in aminoacyl adenylates yield specific products, whereas nucleotides are without effect. For this and related reasons, especially the demonstrated self-sequencing of amino acids when they are warmed, resultant bio-functional properties of self-assembled microstructures, and demonstrated self-sequencing of amino acids in modern systems, the results appear to bridge from the chemical era to the biological period. All the above emerges from a departure in style of research (Young, 1984; Pauling and Zuckerkandl, 1972). The latter authors said, "It appears likely that biogenesis is the passage from a 'non-living system' existing in a large number of states to a 'living' system also existing in a large number of states."(ABSTRACT TRUNCATED AT 250 WORDS)     

Restricted inflammatory reaction in the CNS: a key impediment to axonal regeneration?

Axons in the central nervous system (CNS) of adult mammals do not regenerate after injury. Mammalian CNS differs in this respect from other mammalian tissues, including the peripheral nervous system (PNS), and from the CNS of lower vertebrates. In most parts of the body, including the nervous system, injury triggers an inflammatory reaction involving macrophages. This reaction is needed for tissue healing; when it is delayed or insufficient, healing is incomplete. The CNS, although needing an efficient inflammatory reaction resembling that in the periphery for tissue healing, appears to have lost the ability to supply it. We suggest that restricted CNS recruitment and activation of macrophages are linked to regeneration failure and might reflect the immune privilege that characterizes the mammalian CNS. As macrophages play a critical role in tissue restoration, and because their recruitment and activation are among the most upstream of the events leading to tissue healing, overcoming the deficiencies in these steps might trigger a self-repair process leading to recovery after CNS injury.     

Prolongation of the laryngeal chemoreflex after inhibition of the rostral ventral medulla in piglets: a role in SIDS?

We tested the hypothesis that inhibition of neurons within the rostral ventral medulla (RVM) would prolong the laryngeal chemoreflex (LCR), a putative stimulus in the sudden infant death syndrome (SIDS). We studied the LCR in 19 piglets, age 3-16 days, by injecting 0.05 ml of saline or water into the larynx during wakefulness, non-rapid eye movement (NREM) sleep, and REM sleep, before and after 1 or 10 mM muscimol dialysis in the RVM. Muscimol prolonged the LCR (P < 0.05), and the prolongation was greater when the LCR was stimulated with water compared with saline (P < 0.02). The LCR was longer during NREM sleep than during wakefulness and longest during REM sleep (REM compared with wakefulness). Muscimol had no effect on the likelihood of arousal from sleep after LCR stimulation. We conclude that the RVM provides a tonic facilitatory drive to ventilation that limits the duration of the LCR, and loss of this drive may contribute to the SIDS when combined with stimuli that inhibit respiration.     

The nervous system of Bothriomolus balticus (Proseriata) —a contribution to the knowledge of the orthogon in the Plathelminthes

Summary The nervous system (NS) of Bothriomolus balticus (Proseriata) was studied by the immunocytochemical (ICC) method with antisera to RFamide, SALMFamide and serotonin and with the histochemical GAIF method. The use of the ICC technique provided a much more precise morphological account of the nervous system than had previously been possible. The obtained data are discussed in connection with the comparative morphology of the nerve cords of the Plathelminthes. A similar position does not grant direct correspondence between nerve cords in the taxon Seriata. Marginal cords had probably an independent origin in the Monocelididae and Otoplanidae. The ventral (main) cords of B. balticus seem to correspond to the lateral (main) cords of the Monocelididae. It can be hypothesized that both: (1) a shift of the main cords accompanied by formation of new cords from the plexus and fusion of other cords and (2) a redistribution of nerve processes and perikarya between the cords, take part in the evolution of cords in the Plathelminthes. The first hypothesis seems to explain the difference in the position of main cords in proseriates, though, the second hypothesis might dominate, for example, in the Neorhabdocoela and the Neodermata. The correctness of the evolutionary analysis of the nerve cords in plathelminths can only be provided by neurons or neuron groups marking these structures.