Condition of optimum conduction of synaptic excitation along the dendritic fiber

Existence of an optimum radius of fibre is shown, when physical parameters of the intracellular medium and the nonexcitable dendritic membrane are determined and the length and load resistances are fixed. It provides the maximum potential for one end of the fibre if synaptic conductance is determined for another one. Conductance of excitation along the dendritic fibre of changing thickness is optimum for little synaptic conductance when the fibre radius increases and for high conductance when the radius decreases. The formula for calculating an optimum dendritic spine neck radius is proposed.     

Kainate receptors and the induction of mossy fibre long-term potentiation

There is intense interest in understanding the molecular mechanisms involved in long-term potentiation (LTP) in the hippocampus. Significant progress in our understanding of LTP has followed from studies of glutamate receptors, of which there are four main subtypes (alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), N-methyl-D-aspartate (NMDA), mGlu and kainate). This article summarizes the evidence that the kainate subtype of glutamate receptor is an important trigger for the induction of LTP at mossy fibre synapses in the CA3 region of the hippocampus. The pharmacology of the first selective kainate receptor antagonists, in particular the GLU(K5) subunit selective antagonist LY382884, is described. LY382884 selectively blocks the induction of mossy fibre LTP, in response to a variety of different high-frequency stimulation protocols. This antagonist also inhibits the pronounced synaptic facilitation of mossy fibre transmission that occurs during high-frequency stimulation. These effects are attributed to the presence of presynaptic GLU(K5)-subunit-containing kainate receptors at mossy fibre synapses. Differences in kainate receptor-dependent synaptic facilitation of AMPA and NMDA receptor-mediated synaptic transmission are described. These data are discussed in the context of earlier reports that glutamate receptors are not involved in mossy fibre LTP and more recent experiments using kainate receptor knockout mice, that argue for the involvement of GLU(K6) but not GLU(K5) kainate receptor subunits. We conclude that activation of presynaptic GLU(K5)-containing kainate receptors is an important trigger for the induction of mossy fibre LTP in the hippocampus.     

A new approach to the determination of cardiac potential distributions: application to the analysis of electrode configurations

This paper presents a mathematical model and new solution technique for studying the electric potential in a slab of cardiac tissue. The model is based on the bidomain representation of cardiac tissue and also allows for the effects of fibre rotation between the epicardium and the endocardium. A detailed solution method, based on Fourier Series and a simple one-dimensional finite difference scheme, for the governing equations for electric potential in the tissue and the blood, is also presented. This method has the advantage that the potential can be calculated only at points where it is required, such as the measuring electrodes. The model is then used to study various electrode configurations which have been proposed to determine cardiac tissue conductivity parameters. Three electrode configurations are analysed in terms of electrode spacing, placement position and the effect of including fibre rotation: the usual surface four-electrode configuration; a single vertical analogue of this and a two probe configuration, which has the current electrodes on one probe and the measuring electrodes on the other, a fixed distance away. It is found that including fibre rotation has no effect on the potentials measured in the first two cases; however, in the two probe case, non-zero fibre rotation causes a significant drop in the voltage measured. This leads to the conclusion that it is necessary to include the effects of fibre rotation in any model which involves the use of multiple plunge electrodes.     

Involvement of excitatory amino acid receptors in long-term potentiation in the Schaffer collateral-commissural pathway of rat hippocampal slices.

The present article reviews studies from our laboratory, which have shown that excitatory amino acids receptors of the N-methyl-D-aspartate type are involved in the induction of long-term potentiation in the Schaffer collateral-commissural pathway of rat hippocampal slices. The nature of the excitatory amino acid receptors that mediate the response that is modified by the induction of long-term potentiation is also considered. The mechanism of induction of long-term potentiation is discussed, as are some possible stages that are required for the maintenance of this process. Some new data are presented concerning the ability of N-methyl-D-aspartate to potentiate synaptic transmission and to depress the amplitude of the presynaptic fibre volley. Concerning the potentiation, it is shown that brief (1-2 min) perfusion of slices with N-methyl-D-aspartate is sufficient to potentiate synaptic transmission for at least 3 h. The N-methyl-D-aspartate induced depression of the presynaptic fibre volley is shown to be transient and independent of synaptic transmission.     

Comparative histology, histochemistry and innervation of the striated muscle fibers of the peroneus longus muscle

The morphology of the peroneus longus muscle was compared in three Galliformes and five Passeriformes in relation to partial behavioral characteristics. In the quail two fibre types are found, while the muscle of the other species is composed of three fibre types. The frequencies of these fibres are different, especially between Galliformes and Passeriformes. The peroneus longus muscle in the quail is innervated only from the phasic system. The other species show phasic and tonic innervation. There is a correlation between the muscle fibre calibre and the extent of the synaptic gutter.     

Some observations on the fine structure of the giant synapse in the stellate ganglk of the squid,Doryteuphis bleekeri

Summary The fine structure of the synapse between the second-order giant fibre and the third order-giant fibre of the squid Doryteuphis bleekeri was studied by means of electron microscope. In the synaptic region, the two giant fibres are arranged side by side. Many small processes from the third-order giant fibre penetrate the common sheath which separats the adjacent giant axons making synaptic contact with the second order giant axon.The contact surface consists of opposing two plasma membranes of adjacent axons separated by a narrow space of 20–30 m in width. The synaptic membranes are more electron dense and thicker than the other part of the axon membrane. The synaptic vesicles are concentrated exclusively in the presynaptic axon.The fine structural differences between giant synapse in the stellate ganglion of the squid and the giant-to-motor giant synapse of the crayfish were discussed.This work was supported by Grant Number B-3348 from the National Institutes of Health, United States Public Health Service, Department of Health, Education and Welfare.     

Development of the myoneural junction in the rat

Summary The structure of the myoneural junction in the striated muscle of rat embryos and postnatal rats was studied by electron microscopy in order to assess at ultrastructural level the roles of neuronal and muscular elements and the sequence of events resulting in the formation of a functionally mature synaptic organization.From the observations it is concluded that the axon terminals enveloped by Schwann cells contain vesicles prior to apposition of the prospective synaptic membranes. Subsequently, subsarcolemmal thickening of the postsynaptic membrane takes place after the synaptic gap has been formed by disappearance of the teloglial cell from between the synaptic membranes but before the primary synaptic cleft in the strict sense is formed. Secondary synaptic clefts are formed later, when the primary synaptic cleft is regular in width, by local finger-like invaginations of the postsynaptic membrane, which thereafter expand basally, in a plane transverse to the axis of the axon terminal, to resemble flattened flasks. The junction is formed between multinucleated muscle cells and multiple axons, which at first lie side by side and later, when formation of adult-type secondary synaptic clefts is in progress, become separated by folds of the sarcoplasm and the teloglia. In extraocular muscles of adult rats the sarcoplasmic reticulum is closely associated with the postjunctional sarcoplasm.In the light of earlier observations on the development of contractibility after nerve stimulation, cholinesterase histochemistry and muscle fibre physiology, these observations are interpreted to indicate that functional differentiation of the myoneural synapse results from induction by the motor axon and that the association of the sarcoplasmic reticulum with the postjunctional sarcoplasm in adult extraocular muscles is related to modified fibre physiology.The author wishes to thank Prof. Antti Telkkä, M.D., Head of the Electron Microscope Laboratory, University of Helsinki, for placing the electron microscopic facilities at his disposal.     

Ultrastructure of synapses in the nucleus of the trapezoid body of the bat]

The subsynaptic structure of the synapses in the medial nucleus of the trapezoid body was studied in the bat Myotis oxygnatus. The synaptic endings in the nucleus are represented by large-cup-shaped and small loop-shaped terminations. The cup-shaped terminations are formed of large branches originating from a thick myelinated fibre after loss of myelin from it. Each branch forms a series of contacts alternating with vast enlargements of extracellular space, on the body of the cell and its processes. Large branches are filled with synaptic vesicles, neurofilaments and neurotubules, mitochondria; all these components are distributed rather regularly along the branch diameter. In fine branches of the cup the synaptic vesicles are the main and often the only component. The pattern of the cup branch changes as the distance from the main fibre increases, namely the amount of neurofilaments and neurotubules diminishes up to their disappearance, while the amount and the density of synaptic vesicles increases. The small loop-shaped treminals are different from the cup-shaped ones by the composition of the synaptic vesicles and the structure of the contact zone. In addition to agranular vesicles there are also granular ones. Both types of terminations--cup-shaped and loop-shaped ones -- are found both on the bodies and dendrites. On distal portions of dendrites the terminations are disposed in nests.     

The action of some analogues of the excitatory amino acids in the dentate gyrus of the rat

We have confirmed that gamma-D-glutamylglycine and the L-isomer of 2-amino-4-phosphonobutyric acid, and have shown also that L-2-amino-5-phosphonovaleric (L-APV) acid, are antagonists of synaptic excitations of dentate granule cells induced from both lateral and medial perforant paths. The N-methyl-D-aspartic acid (NMDA) antagonist D-APV is without effect. The synaptic antagonists reduce the presynaptic fibre volley particularly in the lateral path, suggesting that a reduced transmitter output contributes to their action. NMDA receptors exist upon the granule cells, but they are not involved with these synaptic process.     

Synaptic competition and the persistence of polyneuronal innervation at frog neuromuscular junctions

Mechanisms governing the elimination of polyneuronal innervation were examined by correlating the morphology and physiology of competing nerve terminals at identified dually innervated neuromuscular junctions in sartorius muscles of adult frogs (Rana pipiens). Synaptic efficacy (endplate potential amplitude per unit nerve terminal length) was presumed to reflect the ability of a terminal to compete for synaptic space. The synaptic efficacies of two terminals at the same synaptic site were found to be surprisingly equal, with a median difference of 33%. Much more variation would be expected if dually innervated junctions were randomly innervated by pairs of terminals having the same range of synaptic efficacy as that found at singly innervated junctions in the same muscle. This finding supports the hypothesis that the weaker input is eliminated from dually innervated junctions when there is a large discrepancy in competitive efficacy, and that both inputs may persist if competitive efficacies are relatively equal. We also tested but failed to find support for the hypothesis that spatial proximity between competing terminals intensifies competition for synaptic space during synapse elimination.     

The pharmacological and physiological profile of glutamate receptors at the Drosophila larval neuromuscular junction

Abstract.  Drosophila larval muscles are commonly used for developmental assessment in regard to various mutations of synaptically relevant molecules. In addition, the molecular sequence of the glutamate receptors on the muscle fibre have been described; however, the pharmacological profiles to known agonists and antagonists have yet to be reported. Here, the responses of N -methyl- d -aspartic acid, α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA), l -glutamate, kainate, quisqualic acid, NBQX, AP5 and DNQX are characterized with regard to synaptic transmission and direct effects on the muscle fibres. The muscle fibres depolarize to application of glutamate or quisqualate and the excitatory postsynaptic potential (EPSP) amplitudes are diminished. Kainate does not alter the muscle membrane potential but does reduce the EPSP amplitude. The known antagonists NBQX, AP5 and DNQX have no substantial effect on synaptic transmission at 1 m m , nor do they block the response of quisqualate. Kainate may be acting as a postsynaptic antagonist or via autoreceptors presynaptically to reduce evoked transmission.     

L-glutamate as an excitatory transmitter at the neuromuscular junction of a beetle larva

The effects of L-glutamate and acetylcholine on the ventral muscle fibres of the larval mealworm Tenebrio molitor were studied by means of microelectrodes. Bath application of L-glutamate at concentrations higher than 1 × 10 ⁴M suppressed excitatory postsynaptic potentials (EPSPs) and evoked both a depolarisation and a reduction in the input resistance of the muscle fibre. In contrast, acetylcholine chloride (up to 1 mM) had no effect at all. Circumscribed spots could be detected on the fibre surface where iontophoretic applications of L-glutamate caused transient depolarizations (glutamate potentials). Focal extracellular recordings revealed that the glutamate sensitive spots were identical with synaptic sites. The reversal potentials of the EPSP and the L-glutamate potential were identical. These results are compatible with the hypothesis that L-glutamate is an excitatory transmitter at the neuromuscular junction.     

The evolution of phylogenetic differences in the efficiency of digestion in ruminants

This study investigates, for the first time (to our knowledge) for any animal group, the evolution of phylogenetic differences in fibre digestibility across a wide range of feeds that differ in potential fibre digestibility (fibre to lignin ratio) in ruminants. Data, collated from the literature, were analysed using a linear mixed model that allows for different sources of random variability, covariates and fixed effects, as well as controlling for phylogenetic relatedness. This approach overcomes the problem of defining boundaries to separate different ruminant feeding styles (browsers, mixed feeders and grazers) by using two covariates that describe the browser-grazer continuum (proportion of grass and proportion of browse in the natural diet of a species). The results indicate that closely related species are more likely to have similar values of fibre digestibility than species that are more distant in the phylogenetic tree. Body mass did not have any significant effect on fibre digestibility. Fibre digestibility is estimated to increase with the proportion of grass and to decrease with the proportion of browse in the natural diet that characterizes the species. We applied an evolutionary model to infer rates of evolution and ancestral states of fibre digestibility; the model indicates that the rate of evolution of fibre digestibility accelerated across time. We suggest that this could be caused by a combination of increasing competition among ruminant species and adaptation to diets rich in fibre, both related to climatically driven environmental changes in the past few million years.     

An endplate potential due to potassium released by the motor nerve impulse

A small endplate potential can be recorded in frog muscle fibres, after all acetylcholine-mediated transmission has been eliminated by pre- or postsynaptic blocking agents (botulinum toxin, calcium lack, manganese, curare, alpha-bungarotoxin). It is usually necessary to hyperpolarize the muscle membrane to detect this 'non-cholinergic' endplate potential. Below--100 mV little or no response is seen; a maximum is reached at about--140 mV, when the amplitude can be as large as 100 microV (endplate current up to about 1 nA). Other characteristic features are: the response shows no quantal fluctuations; its amplitude is not facilitated by repetitive impulses; its size and time course are not noticeably affected by prostigmine, curare or alpha-bungarotoxin; the half-time of decline of the endplate current is approximately 1.7 ms at 20 degrees C, and is lengthened by lowering the temperature with a Q10 of about 1.3; the response is abolished by barium. When iontophoretic pulses of potassium are applied to the endplate, local depolarization is recorded whose amplitude varies with membrane potential similarly to that of the nerve-evoked response. These observations strongly indicate that this 'non-cholinergic', 'non-quantal' endplate potential arises from a rapid synaptic transfer of potassium ions, released by the active nerve terminal into the synaptic cleft and entering the muscle fibre through 'anomalous rectifier' channels in the endplate membrane.     

Making an escape: development and function of the Drosophila giant fibre system

Flies escape danger by jumping into the air and flying away. The giant fibre system (GFS) is the neural circuit that mediates this simple behavioural response to visual stimuli. The sensory signal is received by the giant fibre and relayed to the leg and wing muscle motorneurons. Many of the neurons in the Drosophila GFS are uniquely identifiable and amenable to cell biological, electrophysiological and genetic studies. Here we review the anatomy and development of this system and highlight its utility for studying many aspects of nervous system biology ranging from neural development and synaptic plasticity to the aetiology of neural disorder.     

The structure of the ventral nerve cord of Caenorhabditis elegans.

The nervous system of Caenorhabditis elegans is arranged as a series of fibre bundles which run along internal hypodermal ridges. Most of the sensory integration takes place in a ring of nerve fibres which is wrapped round the pharynx in the head. The body muscles in the head are innervated by motor neurones in this nerve ring while those in the lower part of the body are innervated by a set of motor neurones in a longitudinal fibre bundle which joins the nerve ring, the ventral cord. These motor neurones can be put into five classes on the basis of their morphology and synaptic input. At any one point along the cord only one member from each class has neuromuscular junctions. Members of a given class are arranged in a regular linear sequence in the cord and have non-overlapping fields of motor synaptic activity, the transition between fields of adjacent neurones being sharp and well defined. Members of a given class form gap junctions with neighbouring members of the same class but never to motor neurones of another class. Three of the motor neurone classes receive their synaptic input from a set of interneurones coming from the nerve ring. These interneurones can in turn be grouped into four classes and each of three motor neurone classes receives its synaptic input from a unique combination of interneurone classes. The possible developmental and functional significance of these observations is discussed.     

Calmodulin-dependent protein phosphatase: immunocytochemical localization in chick retina

Calmodulin-dependent protein phosphatase, previously called CaM-BP80 or calcineurin, is present in high concentrations in the central nervous system. The level of the phosphatase has been shown by radioimmunoassay to increase during development in the retinas of embryonic and hatching chicks (Tallant, E.A., and W.Y. Cheung, 1983, Biochemistry, 22:3630-3635). The aims of this study are to immunocytochemically localize the phosphatase in developing and mature retinas and to determine if the phosphatase is present in fractions of retinal synaptic membranes and synaptic junctions. Vibratome slices of fixed chick retina and Western blots of detergent-solubilized retinal fractions are both treated sequentially with rabbit primary antisera and goat anti-rabbit Fab fragments conjugated to peroxidase, and then reacted with hydrogen peroxide and diaminobenzidine. The tissue slices are further processed for electron microscopy. This paper demonstrates the presence of peroxidase reaction product in the retina just before synapse formation. In the outer plexiform layer the product is confined to photoreceptor synaptic terminals, whereas in the inner plexiform layer it is present in synaptic terminals of bipolar cells and in dendrites of ganglion cells. In this latter site the product is present postsynaptically at bipolar and amacrine synapses. The phosphatase is detected in Western blots of both synaptic plasma membrane and synaptic junction fractions.     

Non-lipid osmiophilic granules in the presynaptic neuroplasma of the boutons

Summary Brain, spinal cord and peripheral (sensory and sympathetic) ganglia of cats and rats have been fixed in Susa, imbedded and impregnated on slides with a mixture of osmium tetroxide and egg albumen solution.This method produced small (about one micron) black granules in the boutons around the multipolar nerve cells in the cord and in the medulla. The granules were absent around the other nerve cells in the cortex (pyramidal cells, etc.) and in the peripheral ganglia.These osmiophilic granules may be clusters of synaptic vesicles containing transmitter substance. If the clusters are large enough, as in the boutons, they are visible under the light microscope, if they are smaller;, as in the smaller synaptic knobs, they remain invisible.If the osmiophilic granules are clusters of vesicles containing the transmitter substance, this substance might be an acidic amino acid.