Morphophysiological characteristics of bushy interoceptors

The survey of the existing morphological and physiological classifications of the bushy interoceptors is presented. Dependence of adaptive properties of the receptors on their structure is demonstrated. The bushy receptors can be both quickly- and slowly-adapting: Their adaptive properties evidently depend on viscous-elastic peculiarities of the surrounding tissues. The data on a possible connection between impulse activity of the receptors and the level of their oxidative metabolism are reported. Similarity and differences of the morpho-functional characteristics of the bushy receptors in various animal organs and tissues are established.     

Structuro-functional changes of bushy receptors after reoxygenation

With restarting oxygen supply to the bushy receptors of the frog urinary bladder, a gradual increase of impulse frequency in the afferent neural fibers is observed, with a successive exceed, in some cases, of the initial level and rearrangement of spike rhythmicity according to the type of "spasmodic" discharges. Certain acceleration is noted in vital staining and discoloration of the receptors. This is expressed in shortening coloration time, in increasing rate for accumulation restorative equivalents, in intensified granuloformation. Ultrastructural shifts are mainly demonstrated in normalization of the mitochondrial apparatus.     

Morphological changes in the electrically inactive afferent myelinated nerve fibers of the live clustered neuroreceptor

At attempt has been made to determine morphological criterium of active and inactive alive afferent myelin fibers. Applying electrophysiological control, external diameters in the area of maximal dilatation of the myelin fiber are compared with the neighbouring maximal narrowing of the unmyelinated preterminal. The dilatation coefficient, suggested by the authors of mathematical models of the nervous fiber is taken as the base of estimation. When the dilatation coefficient is more than five, the fiber is considered to be inactive. The active and inactive nervous fibers are stated to possess certain morphological differences. They are observed not only in the first myelin segment area, but in the second one, and sometimes--in the third and fourth segments. Morphological characteristics of these segments make it possible to suggest that electrical impulse can be blocked. From our data it is possible to think that not only the first myelin segment and the first node of Ranvier, but also the successive segment and nodes of Ranvier influence the impulse passing.     

State of the receptors in the wall of the large arteries and veins following the action of impulse acceleration in the organism]

The state of receptors in the wall of the vena cava and pulmonary veins, the pulmonary trunk and the aorta arc was studied in cats subjected to single impulse accelerations within the limits of 8-70 gravitation units during 20-25 msec. Myelinated nerve fibres underwent reactive changes in the form of increased argirophilia, swelling, varicosities. In bushy receptors there appeared the same reactive changes in their preterminal part as well as an excessive growth of terminals. A small part of myelinated fibres and bushy receptors regenerated. Regeneration of the receptor terminals was noted.     

Ultrastructural changes of receptor endings in prolonged action of local anesthetics

Ultrastructural changes of the terminal plates of the bushy receptors in the frog urinary bladder have been studied after two hours' exposition in 0.05% novocaine solution and one hour's exposition in 0.05% dicaine and trimecaine solution. During these periods a steady block of the receptor impulse activity develops. The local anesthetics essentially change ultramicroscopic structure of the terminals. The reaction to the anesthetics investigated has both some features in common and certain peculiarities. At each effect three types of changes can be determined, characterized with various degree of rearrangement in neurilemma, neuroplasm and organelles. Each type of the changes is supposed to reflect a certain phase of the plate reactive response. Specificities of the reaction to novocaine are minimal changes of mitochondria, accumulation of glycogen granules, deformity and decreasing amount of vesicles. Under dicaine effect mitochondria do not change, amount of vesicles increases, their form does not change; under trimecaine effect mitochondria undergo most noticeable alterations. The changes of the terminal plates observed are interpreted as adaptive. The effect of the local anesthetics on the receptors is not limited with the blockade of the sodium canals of the afferent fibers, in parallel, biochemical processes, occurring in cytosol of the terminals also change; their morphological manifestations are the ultrastructural changes observed.     

Volume transmission in activity-dependent regulation of myelinating glia

The importance of neural impulse activity in regulating neuronal plasticity is widely appreciated; increasingly, it is becoming apparent that activity-dependent communication between neurons and glia is critical in regulating many aspects of nervous system development and plasticity. This communication takes place not only at the synapse, but also between premyelinating axons and glia, which form myelin in the PNS and CNS. Recent work indicates that neural impulse activity releases ATP and adenosine from non-synaptic regions of neurons, which activates purinergic receptors on myelinating glia. Acting through this receptor system, neural impulse activity can regulate gene expression, mitosis, differentiation, and myelination of Schwann cells (SCs) and oligodendrocytes, helping coordinate nervous system development with functional activity in the perinatal period. ATP and adenosine have opposite effects on differentiation of Schwann cells and oligodendrocytes, providing a possible explanation for the opposite effects of impulse activity reported on myelination in the CNS and PNS.     

Adenosine: a neuron-glial transmitter promoting myelination in the CNS in response to action potentials

Neuronal activity influences myelination of the brain, but the molecular mechanisms involved are largely unknown. Here, we report that oligodendrocyte progenitor cells (OPCs) express functional adenosine receptors, which are activated in response to action potential firing. Adenosine acts as a potent neuron-glial transmitter to inhibit OPC proliferation, stimulate differentiation, and promote the formation of myelin. This neuron-glial signal provides a molecular mechanism for promoting oligodendrocyte development and myelination in response to impulse activity and may help resolve controversy on the opposite effects of impulse activity on myelination in the central and peripheral nervous systems.     

Structural and functional reactive changes in the bushy interceptor of the frog urinary bladder upon adequate stimulation]

Morphological and functional changes in the bushy receptors of the frog urinary bladder were studied after a definite cystectasia (bladder wall distention). Morphological and electrophysiological parameters were registered synchronously. Under the effect of distention the total rate of afferent impulse activity was demonstrated to increase with a simultaneous increase of the average size of the receptor end-plates and with changing (growing round) in their form. Increment of the average size of the end-plates overtakes that of the distance between two points chosen on the urinary bladder wall; certain shifts are also observed in time parameters for staining the receptors with methylene blue. A possibility is suggested on interconnections of morphological and electrophysiological shifts.     

Metabolic, electrophysiological and structural effects of dicaine and trimecaine on tissue bushy receptors

By means of a complex technique, including electrophysiological control, vital microscopy, cytophotometry and electron microscopy, reaction of the tissue bushy receptors of the frog urinary bladder to the effect of 0.05% solution of tetracaine hydrochloride (TeH) and trimecaine hydrochloride (TrH) has been investigated. Together with fading afferent impulse activity, the level of restorative equivalents increases sharply; this demonstrates that the anaesthetics influence not only plasmolemma but cytosol of the terminal. In neuroplasm of the terminal plates and receptor fibers certain ultrastructural changes take place (rearrangement of organelles, changes in vesicles, accumulation of glycogen granules). These changes are interpreted as functional-adaptive. Simultaneously, the character of vital staining of the receptors also changes (saturation of the colour, granule formation and time of decoloration). Certain specificity is noted in reaction of the receptors to TeH and TrH. The latter alters more essentially the microstructure both at the effect during 2 and 20 min. The effect of the local anaesthetics is evidently determined not only by the membranotropic effect, but by the influence on the cytosol of the terminal.     

On the Transmission of Information through Sensory Neurons

Information about muscle length is transmitted to the cerebellum from muscle spindle receptors through the dorsal spinocerebellar tract (DSCT). The “transinformation” about muscle length in single DSCT fibers was calculated from steady-state spike trains by two different methods, assuming that the decoding mechanisms use a frequency code. By the first method, the number of distinguishable muscle lengths (and thus the transiformation) was determined from the rate of convergence of the mean frequency of firing (with increasing number of intervals). The observation time necessary to estimate the mean frequency of the impulse train with a certain accuracy was independent of the stretch level, even though the number of intervals necessary to make this estimate was different at high and low levels of stretch. By the second method an input frequency-output frequency matrix was calculated. The transinformations and the rate of transinformation was then calculated from this matrix. There was an acceptable agreement in the estimates of transinformation by the two methods. The rates of transinformation are significantly increased by the particular time structure of the discharge patterns of the nerve cells. Consequently, the loss of information due to the synaptic coupling is appreciably reduced.     

Frequency response characteristics of an isolated photoreceptor

The transmembrane voltage change in response to light was studied in the barnacle photoreceptor by using sinusoidal and impulse changes in light intensity. The input-output relation is linear if the transmembrane voltage change does not exceed 10 mV. The frequency response is of low pass character with attenuation beginning at 1 cps. The system can best be represented by a third order transfer function consisting of a first order pole, a complex second order pole, and a transport delay. Lower temperature causes greater high frequency attenuation of the voltage response. Background illumination, depolarization, and wavelength do not affect the frequency response within the linear range. Beyond the linear range the elements of a differentiating process are introduced. This is probably due to a disproportionate increase in cell conductance.     

Distribution of nerve fiber nodes with different cytochemical properties in bushy interoceptors

Distribution of generation zones of the action potential (AP) in the bushy interoceptors of the frog urinary bladder has been studied by means of D. C. Quick and S. G. Waxman cytochemical technique (1977). A positive reaction is obtained from the nodes of the neural fibers and a part of semi-nodi. The dependence of active nodi distribution on the length of the myelin branches is revealed. Three variants in distribution of precipitate are found in the divided fibers. If the distance between the semi-nodi is 60-350 mcm, the precipitate deposits more proximal to the node division. When the distance between the semi-nodi is 1,300-1,650 mcm, the active nodi are in both branches of the divided fiber. When the distance between the semi-nodi is 460-940 mcm, the active nodi are either in one branch only, or no branches give any positive reaction, and the precipitate deposits in the node of branching. Since the precipitate deposition characterizes, according to D. C. Quick and S. G. Waxman (1977) data, the AP generation places, it is possible to suppose that several impulse generators are present in one receptor, when the distance between its semi-nodi is not less than 1,300 mcm. A specific precipitate is supposed to deposit in the plates. It speaks in favour of a great density of transmembranous currents that determine transformation of a mechanical stimulus into a receptory potential.     

Basic fibroblast growth factor high and low affinity binding sites in developing mouse brain, hippocampus and cerebellum.

Fibroblast growth factors (FGFs), first extracted from brain and retina, are potent neurotrophic factors. They stimulate neuroblast proliferation and neuron differentiation and survival. In order to study the spatial and temporal distribution of the target cells in the mouse brain we studied by autoradiography and quantified by image analysis 125I-bFGF binding sites as a function of development. We have revealed the presence of two types of specific bFGF receptors. One is heparitinase sensitive and is co-localized with heparan sulfate proteoglycans of the basement membranes (meninges, choroid plexus and blood vessels). It is not developmentally regulated and corresponds to the low affinity receptors. It may be a storage form. The second type is heparitinase resistant and is modified during development, matching, in the adult, layering of the hippocampus and cerebellum. At 13 days of embryonic development there is a preferential distribution of silver grains on the ecto- and neuroectodermal tissues. In the adult, the labeling is localized on the neural process layers. It likely corresponds to the specific binding to cell high affinity receptors. Binding patterns according to the developmental stages of the brain can be correlated with mitotic, migration and differentiation phases of the neuronal cells.     

Inhibitory interaction of receptor units in the eye of Limulus

The inhibition that is exerted mutually among the receptor units (ommatidia) in the lateral eye of Limulus has been analyzed by recording oscillographically the discharge of nerve impulses in single optic nerve fibers. The discharges from two ommatidia were recorded simultaneously by connecting the bundles containing their optic nerve fibers to separate amplifiers and recording systems. Ommatidia were chosen that were separated by no more than a few millimeters in the eye; they were illuminated independently by separate optical systems. The frequency of the maintained discharge of impulses from each of two ommatidia illuminated steadily is lower when both are illuminated together than when each is illuminated by itself. When only two ommatidia are illuminated, the magnitude of the inhibition of each one depends only on the degree of activity of the other; the activity of each, in turn, is the resultant of the excitation from its respective light stimulus and the inhibition exerted on it by the other. When additional receptors are illuminated in the vicinity of an interacting pair too far from one ommatidium to affect it directly, but near enough to the second to inhibit it, the frequency of discharge of the first increases as it is partially released from the inhibition exerted on it by the second (disinhibition). Disinhibition simulates facilitation; it is an example of indirect effects of interaction taking place over greater distances in the eye than are covered by direct inhibitory interconnections. When only two interacting ommatidia are illuminated, the inhibition exerted on each (decrease of its frequency of discharge) is a linear function of the degree of activity (frequency of discharge) of the other. Below a certain frequency (often different for different receptors) no inhibition is exerted by a receptor. Above this threshold, the rate of increase of inhibition of one receptor with increasing frequency of discharge of the other is constant, and may be at least as high as 0.2 impulse inhibited in one receptor per impulse discharged by the other. For a given pair of interacting receptors, the inhibitory coefficients are not always the same in the two directions of action. The responses to steady illumination of two receptor units that inhibit each other mutually are described quantitatively by two simultaneous linear equations that express concisely all the features discussed above. These equations may be extended and their number supplemented to describe the responses of more than two interacting elements.     

Electrical activity and structural correlates of giant nerve fibers in Kuruma shrimp (Penaeus japonicus)

Morphology and recordings of electrical activity of Kuruma shrimp (Penaeus japonicus) giant medullated nerve fibers were carried out. A pair of giant fibers with external diameter of about 120 μ and 10 μ in myelin thickness were found in the ventral nerve cord. The diameter of the axon is about 10 μ. Thus there is a wide gap between the axon and the external myelin sheath. Each axon is doubly coated directly by Schwann cells and indirectly by the myelin sheath layer which is produced by those Schwann cells. Impulse conduction velocities of these giant fibers showed a range between 90–210 m/sec at about 22°C. Large action potentials (up to 113 mV, rise time of 0.16–0.3 msec, maximum rate of rise of 650–1250 V/sec, half decay time of 0.2–0.3 msec, maximum rate of fall of 250–450 V/sec and total duration of less than 1.5 msec) could be obtained by inserting microelectrodes or by longitudinal insertion of 25 μ diameter capillary electrodes into the gap but no DC-potential difference was observed across the myelin sheath. Transmyelin electrical parameters were very favorable for fast impulse conduction: myelin resistance of 3 × 10⁴ Ω cm²; time constant of 0.38 msec; myelin capacitance of 1.35 × 10^?8 F/cm²; gap fluid resistivity of 23 Ω cm. The existence of nodes of Ranvier could not be demonstrated morphologically, but electrophysiological evidence suggests that a type of saltatory conduction occurs in these giant fibers.     

Rapid conduction and the evolution of giant axons and myelinated fibers

Nervous systems have evolved two basic mechanisms for increasing the conduction speed of the electrical impulse. The first is through axon gigantism: using axons several times larger in diameter than the norm for other large axons, as for example in the well-known case of the squid giant axon. The second is through encasing axons in helical or concentrically wrapped multilamellar sheets of insulating plasma membrane--the myelin sheath. Each mechanism, alone or in combination, is employed in nervous systems of many taxa, both vertebrate and invertebrate. Myelin is a unique way to increase conduction speeds along axons of relatively small caliber. It seems to have arisen independently in evolution several times in vertebrates, annelids and crustacea. Myelinated nerves, regardless of their source, have in common a multilamellar membrane wrapping, and long myelinated segments interspersed with 'nodal' loci where the myelin terminates and the nerve impulse propagates along the axon by 'saltatory' conduction. For all of the differences in detail among the morphologies and biochemistries of the sheath in the different myelinated animal classes, the function is remarkably universal.     

Preparation of the spinal neurons and their bushy receptors for morphophysiological study

A preparation of the sensory neuron of the spinal ganglion with dendritic processes for simultaneous morphological and physiological investigations is described. It consists of a frog urinary bladder with bushy interoceptors in its wall, two vesicle neurons, two abdominal branches of the X spinal nerves and two IX spinal ganglia with ventral and dorsal roots branching off from them. The total length from the receptors to the ganglion neurons is 20-30 mm. In the ganglia a zone of the neuronal bodies localization is found, their processes form receptors; the zone includes as many as 9 neurons, 50-80 mkm in size. A vital fine structure of the ganglion cells and their satellites is traced. There are three types of cells in the ganglion--large, middle and small. Electrophysiological control has demonstrated that the preparation is viable for several hours.     

Evidence that biological activity of NGF is mediated through a novel subclass of high affinity receptors.

Trophic factors, such as NGF, regulate survival and differentiation of many classes of neurons by binding specific receptors. Two types of NGF receptors have been identified, which bind NGF with low and high affinity. The latter mediates the major biological actions of NGF. To determine the relationship between these two receptor types, polyclonal antibodies to the low affinity receptor have been prepared and used in ligand-binding, ligand-cross-linking, and biological assays. These antibodies eliminated binding of NGF to low affinity receptors and to one class of high affinity receptors, but did not prevent binding to a second class of high affinity receptors. The same antibodies did not inhibit NGF-stimulated neuronal survival or neurite outgrowth. Thus, a biologically important class of high affinity NGF receptors is antigenically distinct from the low affinity receptor and may be encoded by a novel gene.     

Functional and morphologic characteristics of limbic cortex maturation during early ontogenesis

Development of the limbic cortical area in postnatal ontogenesis of the rabbit comprises three periods judging by the parameters of impulse activity of neurones and cytoarchitectonic differentiation. The period of stratification and beginning of cellular differentiation functionally corresponds to the manifestation of simple forms of spike activity (single, group) with long inactivation periods (the first week of life). The period of intensive cytoarchitectonic differentiation with separation of the agranular type of the anterior limbic area structure correlates with a more complex neuronal impulse activity (burst discharges), augmenting spectrum of dominating spike frequencies, predominance of phasic activation and specific responses together with a high total neuronal responsiveness to sensory (acoustic) stimuli (the second to third week of life). The period of complete cytoarchitectonic maturation corresponds to the stabilization of functional properties of neurones (the fourth to sixth week of life). The revealed ontogenetic dynamics of morpho-functional reorganizations in the limbic cortex point to its involvement at an early stage of postnatal life in the mechanisms of sensory analysis and of the formation of adequate adaptive reactions.     

Oligodendrocytes as regulators of neuronal networks during early postnatal development

Oligodendrocytes are the glial cells responsible for myelin formation. Myelination occurs during the first postnatal weeks and, in rodents, is completed during the third week after birth. Myelin ensures the fast conduction of the nerve impulse; in the adult, myelin proteins have an inhibitory role on axon growth and regeneration after injury. During brain development, oligodendrocytes precursors originating in multiple locations along the antero-posterior axis actively proliferate and migrate to colonize the whole brain. Whether the initial interactions between oligodendrocytes and neurons might play a functional role before the onset of myelination is still not completely elucidated. In this article, we addressed this question by transgenically targeted ablation of proliferating oligodendrocytes during cerebellum development. Interestingly, we show that depletion of oligodendrocytes at postnatal day 1 (P1) profoundly affects the establishment of cerebellar circuitries. We observed an impressive deregulation in the expression of molecules involved in axon growth, guidance and synaptic plasticity. These effects were accompanied by an outstanding increase of neurofilament staining observed 4 hours after the beginning of the ablation protocol, likely dependent from sprouting of cerebellar fibers. Oligodendrocyte ablation modifies localization and function of ionotropic glutamate receptors in Purkinje neurons. These results show a novel oligodendrocyte function expressed during early postnatal brain development, where these cells participate in the formation of cerebellar circuitries, and influence its development.