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Development of the sensory receptor cells in the utricular macula.

Normal CBA mice were timed for the developmental stage by the vaginal plug technique. The day of copulatory plug observance was designated as gestation day one. The developmental characteristics of the utricular macula sensory epithelium is described on an ultrastructural level from the 15th to the 19th day of gestation (approximate day of birth). The following pertinent observations are reported: (1) the formation of stereocilia begins prior to the 15th day and continues to approximately the 18th day, (2) the formation of the stereocilia suggests a mechanism of gradual transformation of existing cell surface microvilli, (3) the onset of the genesis of stereocilia precedes neuronal contact and cuticular plate formation, (4) stereocilia rootlets are forming before cuticular plate formation, (5) utricular sensory hair cells have undergone significant ultrastructural differentiation prior to the development of synaptic contacts, and (6) nerve chalice formation of type 1 sensory cells begins on the 18th day and is still incomplete at birth.

Animals

Secondary sensory cells in the gravity receptor system of the statocyst of Octopus vulgaris.

The presence of secondary sensory cells in the Octopus gravity receptor system has been demonstrated. In serial thin sections of the receptor cells (hair cells) no axons were found leaving the cells. Instead, synapses were observed with synaptic vesicles lying inside the receptor cells. Both data clearly indicate that the receptor hair cells represent secondary sensory cells. In addition, efferent contacts to the receptor cells could be confirmed.

Animals

On the mechanism of sensory transduction in bacterial chemotaxis.

Sensory transduction in bacterial chemotaxis is beginning to be understood at the molecular level. At the receptor end, we have some considerable knowledge about the molecular properties of chemoreceptors. At the effector end, we know that flagella rotate and that the direction of rotation is determined by attractants and repellents, although we do not yet know the molecular features of the motor and the gear shift. Between the receptors and the effectors is a system for integrating the sensory transduction, which somewhow involves methylation of membrane proteins and possibly a change in membrane potential, but further details of how the mechanism works remain to be elucidated. It seems to us likely that the facts and concepts learned from a study of sensory transduction in bacteria can be applied to answering questions about transduction mechanisms in eukaryotic cells. Examples include the following: How do sensory stimuli produce their effects in sensory receptor cells? How do neurotransmitters act at receptors of postsynaptic cells to produce the variety of effects possible (changes in membrane potential, in secretion, in contraction, etc.)? How do hormones interact with their receptors to bring about various responses?

Carrier Proteins

Diffuse noxious inhibitory controls (DNIC). II. Lack of effect on non-convergent neurones, supraspinal involvement and theoretical implications.

(1) Diffuse noxious inhibitory controls (DNIC) were tested for their effect on noxious only, non-noxious and proprioceptive cells in the dorsal horn of the intact anaesthetized rat. Unlike convergent neurones, as described in the previous paper, there was no effect of DNIC on these neurones. It is concluded that convergent neurones are specifically inhibited by DNIC. (2) The effect of DNIC could not be demonstrated for convergent neurones in the spinal animal. Thus the neuronal substrate for DNIC must involve supraspinal structures. (3) Because of the level of firing in convergent neurones induced by hair and touch receptors, presumably constantly and randomly activated in the freely moving animal, a noxious message arriving at higher centres may be partly masked by this background noise. On the basis of the known role of convergent neurones in nociception, we propose the following mechanism which may interpret this paradoxical convergence: two pools of convergent neurones are influenced by a painful peripheral stimulation, one segmental pool being activated whilst the remaining population of cells is inhibited; the "contrast" between the messages from these two pools may well produce a significant pain signalling output from the convergent dorsal horn cells. (4) These results and their theoretical implications are discussed with regard to the concept of the "analgesic system", certain clinical observations and the paradoxical pain relieving effects of counterirritation and some forms of acupuncture.

Acupuncture Therapy

Electron microscopy of cutaneous nerves and receptors.

Recent ultrastructural observations on the connective tissue sheaths of nerves, Schwann cell-axonal relations, and nerve terminals and receptors are reviewed. It seems likely that endoneurial collagen is formed by perineurial cells during development and postnatally. New observations on "collagen pockets" are presented. Attention is drawn to freeze-fracture studies of peripheral nerve, particularly in relation to junctional complexes associated with compact myelin, and further application of the technique is considered. Current views on Merkel cells, encapsulated endings, and free nerve terminals are discussed.

Animals

A cytologic study of Grandry corpuscle development in chicken toe skin.

The developmental sequence of Grandry corpuscles was traced in the toe skin of embryonic, young and adult chickens by light and electron microscopy. The developing Grandry cells as well as Schwann cells can first be identified at stage 38 (approximately 12 days of incubation) due to the cytoplasmic content of scattered secretory granules of approximately 100 nm in diameter. Such developing Grandry cells are always associated with nerve fibers. During late stages (stages 40-42, 14-16 days of incubation) several immature Grandry cells formed cell clusters in the dermis. Such cell clusters were always in contact with growing nerve tips of Schwann cells. Immature Grandry cells were separated from one another and dispersed in the connective tissue compartment at stages 44-45 (near hatching). By the time of hatching the developing Grandry cells began to have the morphological characteristics of adult cells. They were relatively large in cell diameter (approximately 10 micron) containing numerous secretory granules and bundles of filamentous material. These cells had finger-like cytoplasmic processes. The Grandry cells at this time had an intimate relationship with nerve fibers and satellite cells. The fact that Grandry cells were always associated with nerve fibers throughout development would support the hypothesis that Grandry cells are derived from neural elements, perhaps neural crest. Satellite cells of Grandry corpuscles are apparently derived from Schwann cells. Grandry cells and corpuscles are adult in form by two to three months of age.

Animals

Biochemical studies of taste sensation--VIII. Partial characterization of alanine-binding taste receptor sites of catfish Ictalurus punctatus using mercurials, sulfhydryl reagents, trypsin and phospholipase C.

1. Taste receptors for L-alanine in the channel catfish Ictalurus punctatus have been partially characterized. The binding activity, which is localized to a sedimentable fraction (Fraction P2), was assayed with L-[3H]alanine as the ligand. 2. Addition of HgCl2 or p-mercuribenzoate to the assay at 0.1-1 mM markedly inhibited binding. The effect was not reversible and was unaffected by increased L-alanine in the binding assay. 3. The sulfhydryl reagents iodoacetate, 5,5'-dithiobis(2-nitrobenzoic acid), arsenite, and N-ethylmaleimide did not show appreciable inhibition of binding. The results suggest that the inhibitory effect of mercurials is not on specific sulfhydryl groups at alanine-binding sites. 4. Treatment of Fraction P2 with phospholipase C decreased binding activity and treatment with trypsin led to increased binding activity.

Alanine

Interaction of chemosensory, visual, and statocyst pathways in Hermissenda crassicornis.

Neurons in the cerebropleural ganglia (CPG), photoreceptors in the eye, optic ganglion cells, and statocyst hair cells of the nudibranch mollusk Hermissenda crassicornis responded in specific ways, as recorded intracellularly, to stimulation of the chemosensory pathway originating at the tentacular chemoreceptors as well as to stimulation of the visual pathway originating at the photoreceptors. Synaptic inhibition of photoreceptors occurs via the chemosensory pathway. The possible significance of such intersensory interaction is discussed with reference to preliminary investigation of the animal's gustatory behavior and possible neural mechanisms of behavioral choice.

Animals

Adult-onset of Tangier disease: 1. Morphometric and pathologic studies suggesting delayed degradation of neutral lipids after fiber degeneration.

A 67-year-old woman, with the typical biochemical features of Tangier disease, had a syringomyelia-like syndrome which has now been observed in several patients with symptomatic onset in adult life. She developed progressive facial diplegia, bilateral wasting of hand muscles and loss of sensation over cranial, cervical and brachial dermatomes over 17 years. Nociception alone was first affected, then nociception and thermal discrimination and finally all modalities of sensation. Quantified tests of cutaneous sensation confirmed that sensation was normal in lower limbs but markedly abnormal in upper limbs. Biopsied fascicles of cutaneous nerves from clinically affected (forearm) and from clinically unaffected (leg) regions permitted a comparison of well-advanced and early pathologic lesions, respectively. The selective vulnerability of unmyelinated and small myelinated fibers in affected regions in this disorder has been confirmed. The earliest morphologic abnormalities of myelinated fibers, but seen infrequently, were mitochondrial enlargement and structural abnormality, aggregation of mitochondria and dense bodies and clusters of neurofilaments. Increased numbers of sudanophilic lipid droplets did not seem to form in Schwann cell cytoplasm prior to fiber degeneration. On the contrary, for myelinated fibers there appeared to be an altered process of axonal degeneration from that seen in Wallerian degeneration and in other axonal degenerations. Distinctive linear bands of closely-packed, minute, osmiophilic and clear lipid droplets formed and their further degradation appeared delayed. Although less clearly demonstrated, lipid droplets in Schwann cells of unmyelinated fibers also appeared to form following their degeneration. We would propose that in Tangier disease, the degradation of myelin ovoids to neutral lipid in Schwann cells does not appear to be delayed. However, further degradation of neutral lipid or its transport away from Schwann cells appears to be retarded.

Aged

The ultrastructure of sensory corpuscles in the skin in the hedgehog snout.

The ultrastructure of sensory nerve endings was examined in the snout skin in 3 adult hedgehogs (Erinaceus europaeus). The material was taken intravitally under total anaesthesia and processed in a usual way for the electron microscopy. The corpuscles were evaluated in the individual sections and series sections made through the whole corpuscle. In the superficial layers of the dermis simple sensory corpuscles and free endings were found. The simple sensory corpuscles can be divided into three types. a) Corpuscles containing a greater number of lamellae in the inner core, the lamellae are arranged regularly and are separated by two opposite clefts. The capsule is formed by only several lamellae undoubtedly of fibrocytic origin. b) Corpuscles containing a smaller number of wider lamellae in the inner core situated often at random. The clefts are also irregular and are often closed in the superficial layers of the inner core. The capsule is quite simple mostly formed by a single lamella of fibrocyte which often fails to form a continuous coat of the corpuscle. c) The third type is typical of its inner core being formed by few lamellae arranged irregularly. These corpuscles have no connective tissue capsule and are separated from the environments only by the basement membrane of superficial lamellae of the inner core. The corpuscles of the second type resemble considerably the developmental stages of simple sensory corpuscles as described in the literature in the cat. They are the same in size or smaller than the corpuscles of the first type. The free nerve endings occurred in two forms. a) Flattened (lanciform) nerve terminals. The axon is rich in mitochondria. The sides of the flattened terminal is lined with one to three wide lamellae while the axon reaches as far as the surface of the formation which is covered only with the basement membrane. b) Typical free endings rich in mitochondria which are embedded in the cytoplasm of Schwann cells or occasionally are covered only with the basement membrane. The lanciform endings which are not linked up with the hairs here may represent a transition from free endings to simple sensory corpuscles.

Animals

[Ultrastructural studies of the duck cere with special reference to Grandry and Herbst bodies].

The results of the investigations into the cere of the domestic duck (Anas boscas domestica) and the mallard (Anas platyrhyncha) may be summarized as follows. The parts of ceroma are the epidermis and the corium. The epidermis is a laminated epithelium and the corium consists of fibrous connective tissues. The later one frequently contains mastocytes and pigment cells. There are many blood vessels, Schwann's cells, nerve fibres, Grandry's and Herbst's bodies. The sensory cells of Grandry's bodies are bodies with processes. They are characterized by the round nucleus, dense core vesicles, the small Golgi's complexes, the narrow endoplasmatic ducts and the cytoplasmatic fascicles. In the nerve fibre running between the sensory cells there are plenty of mitochondria but few clear vesicles and neurofilaments. The axolemma, cytolemma, and the empty space lying between these are sharply obvious. In Grandry's bodies with more than one sensory cells the nerve fibre ramifies. In the branches there are no mitochondria. These are replaced by clear vesicles. In Grandry's bodies with one sensory cell the axon ends in a disc growing narrow at its termination. Both of them are full of mitochondria. The terminal disc is characterized by the elliptical bodies and the thickenings of the membrane. Herbst's body consists of three parts. One of these is the inner knob, the other is the inner cavity, the third is the external capsule. The inner knob consists of two series of cells. The number of cells is ten in both rows each. From the cells, 20 to 50 lamina-like processes are originating. The laminar system of every cell is connected with the system of the cell before and behind it, as well as with the laminar system of the other side. In the nerve fibre running between the rows of cells mainly in its terminal part, some groups are formed by mitochondria, the dense-core vesicles, and the elliptical bodies. The inner cavity consists of laminae of different breadths, limited by cavities full of some meshwork. The laminae vary in form and extent. There are among them some ramifying ones, some forms terminating in a point and some of blunt ends. They are characterized by dense and long ribosomeseries, arranged close to one another. The external capsule consists of several parallel laminae, separated from one another by collagenous fibrin fascicles. The laminae are mostly narrow, their cytoplasm is spongoid, they are characterized by egg-shaped cysterns. There is no synaptic organization either in Grandry's or in Herbst's body. The junction between the membrane is to be regarded as a parallel contact in both places.

Animals

The structure and composition of peripheral nerves and nerve roots in the Sprawling mouse.

Peripheral nerves and lumbar nerve roots of Sprawling, a neurological mutant mouse, were examined with light and electron microscopy. The peripheral nerves and the dorsal roots were thin and grey and were composed predominantly of small myelinated and unmyelinated axons. No evidence of axonal or myelin degeneration was found. Quantitative studies showed a marked reduction in the total number of myelinated axons with preponderance of those of 2-5 micron in diameter or less, most marked in the dorsal roots in which there was also an increase in the proportion of axons which were unmyelinated. In the ventral roots there was a deficiency in the contribution formed by myelinated axons of small calibre, probably indicating a deficiency of gamma fibres. Examination of the myelinated axons in nerves and roots showed a normal relationship between fibre size and internodal lengths and number of myelin lamellae. The findings suggest that the genetic defect in Sprawling is responsible for a failure of myelination of sensory axons. The deficiency of large sensory axons and of small motor axons can be correlated with the deficiency of muscle spindles.

Animals

Studies on the sensory hairs of receptor cells in the inner ear.

The crista ampullaris of the semicircular canal in the frog can be isolated and mounted in a chamber so that the sensory hairs can be observed under high magnification in interference-contrast. The cupula is removed and the sensory hairs can be manipulated and their mechanical properties investigated by a microprobe held in a micromanipulator. The hairs appear quite stiff and pivot around their base. When subjected to force they break as if they are brittle. All the cilia within a bundle move together as if joined to one another. Labelling for electron-microscopy with polycationic ferritin reveals that the membrane surrounding the cilia has a surface coat of negatively charged molecules. When the organ is incubated with polycationic ferritin before fixation the sensory hairs agglutinate. Fusion of the membrane surrounding individual sensory hairs also occurs.

Animals

Embryonic and postnatal development of afferent innervation in cat vestibular receptors.

The maturing process of afferent innervation of the vestibular sensory cells in the cat was studied during both the fetal and postnatal stages. Although the type II cells from the 36th day of gestation already have an innervation similar to that found in the adult, it is not the same for the type I receptor cells. Only 75% have a complete innervation from the 7th postnatal day onwards. Most often, the formation of a continuous nerve calyx is caused by the fusion of the neighbouring membranes of the different dendritic elements belonging to the same neuron. Following the polyneuronal innervation of certain type I cells, numerous competition phenomena can be seen between the fibre endings coming from different neurons. The hypothesis that, during ontogenesis, type I cell innervation passes through a stage which corresponds to type II cell innervation is presented in the Discussion.

Afferent Pathways