The innervation of the primate fungiform papilla--development, distribution and changes following selective ablation

The development of the terminal parts of the chorda tympani nerve, lingual nerve and cranial sympathetics in the macaque fungiform papillae were studied by light- and electron microscopy. Their respective distributions in the intra- and extragemmal compartments of papillae from adult macaques were examined following selective ablation of each nerve. Prior to midgestation, a single bundle of unmyelinated axons which contained numerous axoaxonic synapses passed through the subepithelial connective tissue and ramified in the single nascent chemosensory corpuscle and surrounding non-gustatory epithelium. Following midgestation, additional chemosensory corpuscles appeared, possibly by division of existing corpuscles, myelination of axons was begun, axoaxonic synapses were eliminated, and nerve terminals appeared in the subepithelial connective tissue as free nerve endings and coiled simple nerve endings. In the perinatal period, coiled simple endings, corpuscular receptors and Meissner corpuscles were present in the papilla core. Large numbers of intra-epithelial nerve endings were present in the extragemmal epithelium throughout development. Tonofilament collars ensheathed intra-epithelial axons and 80-100 nm dense core granules, occupying adjacent epithelial cells, appeared to be sequestered near such axons. Experimental selective ablation indicated that the terminal parts of chorda tympani fibers were present only within chemosensory corpuscles. In contrast, lingual nerve endings were present both in the extragemmal epithelium and chemosensory corpuscles and also were the sole supply of corpuscular receptors. Sympathetics appeared to be sparsely distributed in the papilla core. Intra-epithelial axons degenerated within 24 h following transection, while axons with Schwann or lamellar cell sheaths or myelin persisted for at least 3 days.     

The sensory innervation of primate facial skin. II. Vermilion border and mucosa of lip

The innervation of the vermilion border and mucosa of the monkey lip have been studied by light and election microscopy. Meissner corpuscles are present at the junction between hairy skin and vermilion border usually high in the dermal papillae, tightly abutting the overlying basal layer of the keratinized squamous epithelium. These Meissner corpuscles resemble those described in primate glabrous skin and are characterized by the presence of stacks of lamellae interposed between loops of the terminal axon. The lamellae are cytoplasmic extensions of specialized Schwann cells referred to as lamellar cells. One to three myelinated axons, 2–4 μm in diameter, innervate a single Meissner corpuscle.Coiled simple corpuscles, innervated by 1–3 myelinated axons, 3–5 μm in diameter, are characteristic of the non-keratinized portion of vermilion border and oral mucosa. The terminal axons in simple corpuscles are enveloped by circumferentially arranged cytoplasmic lamellae. Small terminal axoplasmic spikes protrude into spaces between the cytoplasmic lamellae in both Meissner and simple corpuscles. Cytoplasmic lamellae in both receptors are characterized by the presence of numerous pinocytotic vesicles. The lower parts of Meissner as well as simple corpuscles are encapsulated by perineurium and these perineural epithelial cells have incomplete basal lamina on both sides of their flattened cytoplasm. In contrast, corpuscles that are present high in the dermal papillae have scant perineural capsular elements and instead have fibroblast-like cells demarcating the inner core of the corpuscle from the general connective tissue compartment. Endoneural fibroblasts are a constant component of all corpuscular receptors. Tactoids of fibrous long-spacing collagen are present in the endoneural connective tissue of these sensory corpuscles. The vermilion border has 10–20 corpuscular receptors per mm² of surface area. Tastscheiben consisting of clusters of Merkel cells and their associated axons are present in the basal layer of rete ridges and rete pegs throughout the hair skin, vermilion border, and oral mucosa of the primate lip.Free nerve endings (FNE's) have been identified using cytologie criteria described previously⁵⁴. FNE's in the vermilion border and mucosa often establish intimate contact with the basal lamina and/or basal cells of the epithelium. FNE's can also be identified in dermal papillae that contain Meissner and/or simple corpuscles. Ruffini nerve endings are not present in dermal papillae. This relatively dense sensory innervation can be correlated with the known tactile sensitivity of the lip in terms of twopoint as well as force thresholds and expanded areas of thalamic and cortical representation.The innervation of glabrous skin resembles that of hairy skin with Meissner and simple corpuscles of glabrous skin being equivalent to lanceolate terminals of hairy skin. The other sensory terminals of each type of skin are identical. Hairs provide an anatomical substrate for multiple afferent terminals, and rete ridges/dermal papillae are the equivalent structural unit in glabrous skin. Each cutaneous anatomical site can be multiply innervated, and this afferent information is processed centrally over multiple parallel ascending systems.     

Early development and innervation of taste bud-bearing papillae on the rat tongue

Early development of fungiform papillae on the fetal rat tongue was examined: (1) to determine whether morphogenesis of the taste bud-bearing fungiform papillae is induced by nerve and (2) to study the growth pattern of the two sensory nerves that innervate the papilla. The papillae first appear on the 15th day of gestation (E15; E1 is the day when the dam is sperm positive) in rows parallel to the midline sulcus. There appears to be a medial-lateral and an anterior-posterior gradient in the sequence of papilla differentiation. The epithelium of the early papilla resembles a multilayered placode topped by a flattened surface periderm. Close examination of the peridermal cells at the apex of the papillae reveals that the cells have fewer surface microvilli and their cytoplasm is more electron opaque than that of similar cells in interpapillary regions. The basal cells in the placode-like epithelium differ from those in interpapillary regions in that they are postmitotic and have more mitochondria. At later stages, the papilla acquires a mesenchymal core and nerves grow into the core. Results from organ culture experiments of tongue fragments taken from E14 fetuses indicate that morphogenesis of fungiform papillae is initiated in the absence of sensory nerve influence, but the nerve exerts a trophic effect on their maintenance. The two sensory nerves of the tongue, the chorda tympani and the lingual branch of the trigeminal nerve, enter the tongue mesenchyme at E14 and grow toward the epithelium. By E15 the chorda tympani branches have reached the developing fungiform papillae, by E16 many have entered the papilla, and by E17 they have penetrated the epithelium at the papilla apex. Their fibers are associated exclusively with the cells at the papilla apex, where the taste bud will develop. The trigeminal nerve ramifies beneath the surface of the entire epithelium by E15. Later, it, too, sends branches into fungiform papillae; these ascend along the trunk of the chorda tympani and at E17 terminate in the connective tissue core around the chorda tympani field. The results are compatible with the notion that the tongue epithelium exerts a general tropic effect on growing axons of both sensory nerves, and the epithelial cells of the fungiform papilla apex exert a similar effect to which only the chorda tympani axons are responsive.     

Immunohistochemical,electrophysiological, and electron microscopical study of rat fungiform taste buds after regeneration of chorda tympani through the non-gustatory lingual nerve

The sensory innervation of fungiform papillae on the rat dorsal tongue is derived from branches of two cranial nerves: the lingual branch of the trigeminal nerve which provides somatosensory innervation and the chorda tympani (CT) branch of the facial nerve, which provides innervation to the taste buds. Removal of the CT results in degeneration of the taste buds. Removal of both nerves results in reduction in size of fungiform papillae and an altered pattern of keratinization in its epithelium. Regeneration of nerves to the epithelium restores the pre-operative condition. Thus, in addition to their sensory functions, both the CT and lingual seem to exert trophic effects on the phenotypic expression of epithelial cells in the fungiform papillae. We severed both the CT and lingual nerves in rats and sutured the proximal stump of the CT to the distal stump of the lingual to promote regeneration of the CT along the lingual nerve pathway. At the same time, we prevented the proximal stump of the lingual from regenerating into the tongue. Our purpose was to determine whether and how the innervation pattern of the regenerated taste bud might be different from normal under these experimental conditions. We found that reinnervation by the CT through the lingual nerve occurs, that this restores the anatomical and functional integrity of the fungiform taste buds and papillae, and that some papillae, but not all, were richly innervated with subgemmal, extragemmal, and perigemmal neuron-specific enolase, calcitonin gene-related peptide, substance P, and neurokinin A-positive fibers. Moreover, responses to taste stimuli were recorded electrophysiologically from the CT. © 1996 Wiley-Liss, Inc.     

5′-Nucleotidase in the rodent ventral striatum: Relation to the distribution of leu-enkephalin,cell clusters,and infralimbic cortical innervation

The goal of this study was to determine the compartmental organization of 5′-nucleotidase within the rodent ventral striatum and to compare the distribution of 5′-nucleotidase with that of leu-enkephalin, cell clusters, and infralimbic cortical innervation. In the core, 5′-nucleotidase is present in several contiguous patchy structures that are in register with leu-enkephalin compartments. In the shell, 5′-nucleotidase is concentrated in a longitudinal band along the septal border. This “medial band” extends from the rostral pole of the ventral striatum to the bed nucleus of stria terminalis. The ventral portion of the medial band is in register with a cluster of cells, located medial to the most dorsal island of Cajella. A second 5′-nucleotidase compartment along the border of the core and shell is in register with a cell cluster and is most evident at caudal levels of the ventral striatum. The innervation of the ventral striatum by the infralimbic cortex is denser in the shell than in the core. In the shell, fibers from the superficial layers of the infralimbic cortex tend to avoid the 5′-nucleotidase-rich cell clusters and terminate in areas of moderate 5′-nucleotidase density. By contrast, fibers from the deep layers terminate in the ventral striatum without regard to the 5′-nucleotidase-rich cell clusters. Overall, the compartmental structure of 5′-nucleotidase in the ventral striatum segregates projections from different layers of the infralimbic cortex. Dense 5′-nucleotidase compartments are innervated by neurons in the deep layers of the infralimbic cortex. The area of moderate 5′-nucleotidase density surrounding the 5′-nucleotidase compartments is innervated by neurons in both the superficial and deep layers. © 1995 Wiley-Liss, Inc.     

The Expression of α-, β-, and γ-Synucleins in Olfactory Mucosa from Patients with and without Neurodegenerative Diseases

A family of homologous proteins known as α-, β-, and γ-synuclein are abundantly expressed in brain, especially in the presynaptic terminal of neurons. Although the precise function of these proteins remains unknown, α-synuclein has been implicated in synaptic plasticity associated with avian song learning as well as in the pathogenesis of Parkinson's disease (PD), dementia with LBs (DLB), some forms of Alzheimer's disease (AD), and multiple system atrophy (MSA). Since olfactory dysfunction is a common feature of these disorders and the olfactory receptor neurons (ORNs) of the olfactory epithelium (OE) regenerate throughout the lifespan, we used antibodies specific for α-, β-, and γ-synucleins to examine the olfactory mucosa of patients with PD, DLB, AD, MSA, and controls without a neurological disorder. Although antibodies to α- and β-synucleins detected abnormal dystrophic neurites in the OE of patients with neurodegenerative disorders, similar pathology was also seen in the OE of controls. More significantly, we show here for the first time that α-, β-, and γ-synucleins are differentially expressed in cells of the OE and respiratory epithelium and that α-synuclein is the most abundant synuclein in the olfactory mucosa, where it is prominently expressed in ORNs. Moreover, α- and γ-synucleins also were prominent in the OE basal cells, which include the progenitor cells of the ORNs in the OE. Thus, our data on synuclein expression within the OE may signify that synuclein plays a role in the regeneration and plasticity of ORNs in the adult human OE.     

Zona incerta and lateral hypothalamic afferents to the midbrain reticular core of cat — An HRP and electrophysiological study

The zona incerta (ZI) and lateral hypothalamic afferents to the midbrain reticular formation (MRF) of cat were investigated with the horseradish peroxidase (HRP) technique and by using antidromic identification in experiments on chronically implanted, behaving preparations.Following HRP injections restricted to the MRF territory (nucleus cuneiformis and central tegmental field), the largest number of retrogradely labeled cells appeared in the medial third of the ipsilateral ZI. Labeling extended medially to the adjacent lateral hypothalamus. The number of positive elements gradually diminished towards the lateral extremity of the ZI and the continuing reticularis thalamic nucleus. Ventral lateral geniculate neurons were consistently labeled. No positive elements were found in ventrobasal, pulvinar-lateralis posterior and ventralis lateralis thalamic nuclei.The MRF-evoked antidromic invasion of ZI cells occurred with a sharp mode between 0.5 and 0.75 ms (median latency of the whole sample: 0.6 ms). The conduction velocity of theZI→MRF axons is twice as high as the values found in the reciprocalMRF→ZI projection. In addition to the antidromically elicited discharges, MRF stimulation resulted in short-latency synaptic excitation, sometimes following the antidromic invasion of the same neuron. The difference between the discharge rates of ZI neurons during EEG-desynchronized and EEG-synchronized behavioral states was not significant. A statistically significant increase in firing rates was found in ZI neurons during waking periods with movements compared to quiet, motionless epochs of waking. The possible involvement of caudally projecting ZI cells in the preparation of postural and/or phasic motor functions is discussed.     

Simultaneous monitoring of the seizure-related changes in extracellular glutamate and γ-aminobutyric acid concentration in bilateral hippocampi following development of amygdaloid kindling

We simultaneously monitored the seizure-related changes in extracellular hippocampal glutamate (Glu) and γ-aminobutyric acid (GABA) concentration in brain dialysates in order to clarify the role of Glu and GABA in the development of kindling. Brain dialysates were collected every 5 min from 10 min prior to 80 min after stimulus in the three developing conditions consisting of pre-kindling state, stage 3 (C-3), and five consecutive stage 5 (5*C-5) following kindling in the same rat. Extracellular Glu level increased rapidly, lasting for only 5 min after stimulus. The post-stimulus ratio of Glu increase in partially kindled rats (C-3) was 2.5–3.5 times of the baseline, and in fully kindled rats it was about 5 times of the baseline. Extracellular GABA concentration enhanced gradually, reaching a plateau level at 15–20 min and lasting for several hours after stimulus at each stage. The enhancement of GABA level was about 1.5 times of the baseline in partially kindled stage, and was about 2.5 times of the baseline in fully kindled stage. There was no significant difference between the two hemispheres with respect to either the time-course or the magnitude of Glu and GABA increase respectively. These data show that progressive, transient and stimulus-induced enhancement of extracellular Gin levels combined with long-lasting elevation of extracellular GABA levels in the bilateral ventral hippocampi results in imbalance between the excitatory and inhibitory neuronal systems, causing excessive propagation of seizure activity, culminating in the secondary generalized seizure of amygdaloid kindling.     

The development, use, and reliability of the Brief Psychiatric Rating Scale (Nursing Modification)—An assessment procedure for the nursing team in clinical and research settings

The role of nursing staff in the systematic rating of psychopathology has been explored in a small number of studies in recent years. Nurses are uniquely placed to carry out relatively continuous observations of high validity which are sensitive to change, yet on the basis of the limited data available, some doubts remain concerning the reliability of such ratings, particularly when they extend to nonobservational phenomena. Nevertheless, since in practice nurse ratings form an important part of the psychopathological assessment arm in many research settings, continuing uncertainty about their reliability is clearly undesirable. Following a brief review of nurse rating, this report describes the role of the nursing team in a developing research environment and reports interrater reliability data for randomly selected pairings of nurses drawn from a mainstream clinical team who had been trained in the use of a specially modified version of the Brief Psychiatric Rating Scale (Nursing Modification) (BPRS[NM]). The findings indicate that nursing staff can reliably rate this range of psychopathology under ordinary clinical conditions, provided they have been properly trained and that appropriate modifications have been made to the procedure. Although validity was not formally assessed in this study, the extension of the time period covered by the BPRS, combined with the special place of nurses in the ward milieu can also be expected to enhance the validity and sensitivity of the ratings. Other effects of the involvement of therapeutically-oriented nursing staff in research procedures are also discussed.     

Localization,distribution, and connectivity of neuropeptide Y in the human and porcine retinas—A comparative study

Neuropeptide Y (NPY) is a peptide neurotransmitter abundantly expressed in the mammalian retina. Since its discovery, NPY has been studied in retinas of several species, but detailed characterization of morphology, cell‐type, and connectivity has never been conducted in larger mammals including humans and pigs. As the pig due to size and cellular composition is a well‐suited animal for retinal research, we chose to compare the endogenous NPY system of the human retina to that of pigs to support future research in this field. In the present study, using immunohistochemistry, confocal microscopy and 3D reconstructions, we found NPY to be expressed in GABAergic and calretinin‐immunoreactive (‐ir) amacrine cells of both species as well as parvalbumin‐ir amacrine cells of humans. Furthermore, we identified at least two different types of medium‐ to wide‐field NPY‐ir amacrine cells. Finally, we detected likely synaptic appositions between the NPY‐ir amacrine cells and melanopsin‐ and nonmelanopsin‐ir ganglion cells, GABAergic and dopaminergic amacrine cells, rod bipolar cells, and horizontal cells, suggesting that NPY‐ir cells play diverse roles in modulation of both image and non‐image forming retinal signaling. These findings extend existing knowledge on NPY and NPY‐expressing cells in the human and porcine retina showing a high degree of comparability. The extensive distribution and connectivity of NPY‐ir cells described in the present study further highlights the potential importance of NPY signaling in retinal function.     

Effects of hypoxia‐induced gill remodelling on the innervation and distribution of ionocytes in the gill of goldfish,Carassius auratus

The presence of an interlamellar cell mass (ILCM) on the gills of goldfish acclimated to 7°C leads to preferential distribution of branchial ionocytes to the distal edges of the ILCM, where they are likely to remain in contact with the water and hence remain functional. Upon exposure to hypoxia, the ILCM retracts, and the ionocytes become localized to the lamellar surfaces and on the filament epithelium, owing to their migration and the differentiation of new ionocytes from progenitor cells. Here we demonstrate that the majority of the ionocytes receive neuronal innervation, which led us to assess the consequences of ionocyte migration and differentiation during hypoxic gill remodelling on the pattern and extent of ionocyte neuronal innervation. Normoxic 7°C goldfish (ILCM present) possessed significantly greater numbers of ionocytes/mm² (951.2 ± 94.3) than their 25°C conspecifics (ILCM absent; 363.1 ± 49.6) but a statistically lower percentage of innervated ionocytes (83.1% ± 1.0% compared with 87.8% ± 1.3%). After 1 week of exposure of goldfish to hypoxia, the pool of branchial ionocytes was composed largely of pre‐existing migrating cells (555.6 ± 38.1/mm²) and to a lesser extent newly formed ionocytes (226.7 ± 15.1/mm²). The percentage of new (relative to pre‐existing) ionocytes remained relatively constant (at ～30%) after 1 or 2 weeks of normoxic recovery. After hypoxia, pre‐existing ionocytes expressed a greater percentage of innervation than newly formed ionocytes in all treatment groups; however, their percentage innervation steadily decreased over 2 weeks of normoxic recovery. J. Comp. Neurol. 522:118–130, 2014. © The Authors. The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.     

A community needs assessment: the care needs assessment pack for dementia (CarenapD)—its development,reliability and validity

Objective. To develop and evaluate a multidisciplinary needs assessment tool for people with dementia living in the community and their carers. Design. The measure was developed through applying a theory of need, generating content, consultation with potential users and refinement and evaluation. Validity was established incrementally through the development process. Setting. The development and evaluation was conducted in a variety of settings, including multidisciplinary dementia community care teams, social work departments, day hospitals, and inpatient and residential care. Patients. The evaluation included community patients with a formal diagnosis of dementia (N=34) and consultation with a multidisciplinary group of potential users (N=23). The development process included inpatients with a formal diagnosis of dementia (N=157) and consultation with potential users (N=170) from a range of professions including both health and social care. Measures. Interrater reliability was assessed using the kappa statistic. Social validity was estimated using a measure developed for this purpose as part of the development process. Results. The evaluation of interrater reliability demonstrated that three-quarters of assessors agreed on at least 85% of items in the CarenapD. The kappa statistic demonstrated that agreement for 76.2% of items in the CarenapD was ‘good’ or better (ie kappa>0.75), for 12.4% of items it was ‘fair’ or ‘moderate’ (ie kappa 0.35–0.60) and for the remaining 12 (11.4%) items for which kappa could not be calculated there was low intra-item variance and high agreement (>90%). There was good evidence for social validity. Conclusions. The CarenapD is a reliable and valid multidisciplinary assessment of need for people with dementia living in the community and their carers. © 1998 John Wiley & Sons, Ltd.     

Singing Numbers… in Cognitive Space — A Dual‐Task Study of the Link Between Pitch,Space, and Numbers

We assessed the automaticity of spatial‐numerical and spatial‐musical associations by testing their intentionality and load sensitivity in a dual‐task paradigm. In separate sessions, 16 healthy adults performed magnitude and pitch comparisons on sung numbers with variable pitch. Stimuli and response alternatives were identical, but the relevant stimulus attribute (pitch or number) differed between tasks. Concomitant tasks required retention of either color or location information. Results show that spatial associations of both magnitude and pitch are load sensitive and that the spatial association for pitch is more powerful than that for magnitude. These findings argue against the automaticity of spatial mappings in either stimulus dimension.     

The progression of neuronal,myelin, astrocytic,and immunological changes in the rat brain following exposure to aurothioglucose

Aurothioglucose (ATG) is presently employed both by clinicians in the treatment of advanced rheumatoid arthritis and by neuroscience researchers to generate lesions around the circumventricular organs (CVOs) of rodent brains, resulting in obese animals. Although the existence of such lesions is well documented, there is relatively little information concerning the changes over time of the different cell types in the regions surrounding the CVOs. To address this question, specific markers allowing identification of four distinct cellular populations were used to characterize respective changes over time. Generally, regions adjacent to the CVOs were more vulnerable than the CVOs themselves, while more caudal structures were more frequently lesioned than more anterior CVO regions. Vascular and glial cells appeared to be the initial targets of ATG, while neuronal cell death occurred subsequent to the inflammatory response. The results of this study help resolve the mechanism of ATG toxicity as reflected by a cascade of pathologies that is consistent with disparate cell types exhibiting specific changes at specific times.     

Dog cerebral cortex contains μ-, δ- and κ-opioid receptors at different densities: apparent lack of evidence for subtypes of the κ-receptor using selective radioligands

The biochemical and pharmacological properties of mu (mu), kappa (kappa) and delta (delta) opioid receptors were ascertained in dog cerebral cortex homogenates. The selective peptides, [3H]D-Pen2-D-Pen5enkephalin [( 3H]DPDPE) and [3H]D-Ala2-MePhe4-Glyol5-enkephalin [3H]Glyol; [3H]DAMGO), bound to delta- and mu-opioid receptors with high affinity (dissociation constants, Kd values = 4.7 and 1.6 nM) but to different densities of binding sites (Bmax values of 49.2 and 6.6 fmol/mg protein, respectively) in washed homogenates of dog cerebral cortex. In contrast, the non-peptides, [3H]U69593 [( 3H]U69) and [3H]etorphine [( 3H]ET), labeled a high concentration of kappa-opioid receptors (respective Bmax values of 67.2 and 76.6 fmol/mg protein) of high affinity (respective Kds of 1.4 and 0.47 nM) in the same tissue homogenates. Thus, the relative rank order of opioid receptor densities was: kappa greater than delta much greater than mu. The selective labeling of the kappa-receptors with two different drugs [( 3H]U69 and [3H]ET) failed to reveal the possible existence of multiple kappa-sites based on the relative Bmax values of the two radioligands. This conclusion was further supported by the similarity of the pharmacological specificity of both [3H]U69 and [3H]ET binding, where all the opioids tested produced 100% inhibition of these labels and where the rank order of potency of opioids at inhibiting the binding of these probes was: U50488 greater than U69593 greater than dynorphin-(1-8) greater than naloxone much greater than morphine much greater than Glyol (DAMGO) greater than DPDPE.(ABSTRACT TRUNCATED AT 250 WORDS)