About functional evolution of peripheral part of the auditory system

Functional evolution of the peripheral part of the auditory system is considered. The key point of the appearance of a possibility of analysis of sound waved is formation in the course of evolution of cells with protoplasmic processes (sensillae)—the hair cells—that are transformed into auditory receptors. The fundamental moment is the emergence in evolution of the specialized ionic medium (endolymph) surrounding the auditory receptors. This medium is necessary for generation of receptor potential due to mechanical deformations of the auditory receptor. The characteristic feature of functional evolution of the peripheral part of the auditory system is the many-time repetition in the course of evolution of the main devices to detect and to distinguish sounds. This indicates recapitulation in evolution not only of the central parts of the brain (including central regions of the auditory system), but also of its peripheral part.     

Peripheral frequency mis-match in the primitive ensiferan Cyphoderris monstrosa (Orthoptera: Haglidae)

Peripheral auditory frequency tuning in the ensiferan insect Cyphoderris monstrosa (Orthoptera: Haglidae) was examined by comparing tympanal vibrations and primary auditory receptor responses. In this species there is a mis-match between the frequency of maximal auditory sensitivity and the frequency content of the species' acoustic signals. The mis-match is not a function of the mechanical properties of the tympanum, but is evident at the level of primary receptors. There are two classes of primary receptors: low-tuned and broadly tuned. Differences in the absolute sensitivity of the two receptor types at the male song frequency would allow the auditory system to discriminate intraspecific signals from sounds containing lower frequencies. Comparisons of tympanal and receptor tuning indicated that the sensitivity of the broadly tuned receptors did not differ from that of the tympanum, while low-tuned receptors had significantly narrower frequency tuning. The results suggest that the limited specialization for the encoding of intraspecific signals in the auditory system of C. monstrosa is a primitive rather than a degenerate condition. The limited specialization of C. monstrosa may reflect the evolutionary origin of communication-related hearing from a generalized precursor through the addition of peripheral adaptations (tympana, additional receptors) to enhance frequency sensitivity and discrimination. Accepted: 13 March 1999     

Receptors of glutamate and neurotrophin in vestibular neuronal functions

The last decade has witnessed advances in understanding the roles of receptors of neurotrophin and glutamate in the vestibular system. In the first section of this review, the biological actions of neurotrophins and their receptors in the peripheral and central vestibular systems are summarized. Emphasis will be placed on the roles of neurotrophins in developmental plasticity and in the maintenance of vestibular function in the adult animal. This is reviewed in relation to the developmental expression pattern of neurotrophins and their receptors within the vestibular nuclei. The second part is focused on the functional role of different glutamate receptors on central vestibular neurons. The developmental expression pattern of glutamate receptor subunits within the vestibular nuclei is reviewed in relation to the potential role of glutamate receptors in regulating the development of vestibular function.     

Tonotopic organization of auditory receptors of the bushcricket Pholidoptera griseoaptera (Tettigoniidae, Decticinae)

The peripheral and central tonotopy of auditory receptors of the bushcricket Pholidoptera griseoaptera is described. Out of 24 auditory receptor cells of the crista acustica 18 were identified by single-cell recordings in the prothoracic ganglion and complete staining with neurobiotin. Proximal receptor cells of the crista acustica were most sensitive to 6 kHz, with medial cells being sensitive to 20–30 kHz, whereas distal cells were most sensitive to frequencies higher than 50 kHz. Projection areas within the auditory neuropile in the prothoracic ganglion were to- notopically arranged. Proximal cells projected anteriorly, medial cells ventrally and posteriorly, and distal cells to more dorsal regions. Identified receptor cells revealed an interindividual variability of tuning and central projections. Receptor cells from the intermediate organ of a bushcricket were identified for the first time. Receptors of the distal intermediate organ were broadly tuned and less sensitive than those of the crista acustica. Receptor cells of the proximal intermediate organ were most sensitive to frequencies below 10 kHz. They projected in anterior portions of the auditory neuropile, whereas cells of the distal intermediate organ had terminations spread over almost the whole auditory neuropile.     

Embryonic development of the central projection of auditory afferents (Schistocerca gregaria, Orthoptera, Insecta)

The auditory system of Schistocerca gregaria is a well investigated sensory network in the adult grasshopper. Here we present a first study on the embryonic development of this neuronal network. Focussing on the auditory receptor cells we show that they differentiate axonal processes at around 45% of embryonic development. These axons fasciculate with the intersegmental nerve and enter the central nervous system by 45-50% of development. First collaterals sprout into the major arborization area, the frontal auditory projection area of the metathoracic ganglion by 60%. This projection increases in density until an adult-like morphology is established by 90% of development. Furthermore, by the end of embryogenesis all three types of receptor fiber projections can be distinguished. This development is independent of a hearing ability, which develops much later during postembryonic life. The auditory projection co-develops with the fusion of neuromeres to the metathoracic ganglion, the formation of the target neuropile areas and the expression of the synapse associated molecule synapsin. Fasciclin I and Lachesin, both potential axon-guidance molecules, are expressed strongly on both, peripheral and central auditory pathways and, although much weaker, within the synaptic target area.     

Anti-inflammatory effect of acute stress on experimental colitis is mediated by cholecystokinin-B receptors

We aimed to investigate the effects of electric shock (ES) on the course of experimental colitis and the involvement of possible central and peripheral mechanisms. In Sprague-Dawley rats (n = 190) colitis was induced by intracolonic administration 2,4,6-trinitrobenzenesulfonic acid (TNBS). The effects of ES (0.3-0.5 mA) or the central administration of corticotropin-releasing factor (CRF; astressin, 10 microg/kg) or cholecystokinin (CCKB; 20 microg/kg) receptor antagonists and peripheral glucocorticoid receptor (RU-486; 10 mg/kg) or ganglion (hexamethonium; 15 mg/kg) blockers on TNBS-induced colitis were studied by the assessment of macroscopic score, histological analysis and tissue myeloperoxidase activity. ES reduced all colonic damage scores (p < 0.05-0.01), while central CRF (p < 0.05-0.001) and CCKB receptor (p < 0.05-0.01) blockers or peripheral hexamethonium (p < 0.05-0.01) and RU-486 (p < 0.05) reversed stress-induced improvement. ES demonstrated an anti-inflammatory effect on colitis, which appears to be mediated by central CRF and CCK receptors with the participation of hypothalamo-pituitary-adrenal axis and the sympathetic nervous system.     

Intracellular routing of transferrin and transferrin receptors in epidermoid carcinoma A431 cells

Using transferrin peroxidase (Tfn-HRP) and a transferrin receptor-specific antibody complexed to colloidal gold (ATR) we have identified the intracellular compartments concerned with processing internalized transferrin-receptor complexes. We have identified major membrane-bound systems in the peripheral cytoplasm and in the juxtanuclear area, from which components of these complexes are returned to the cell surface. Time course studies indicate that the peripheral system is concerned with a “short circuit,” recycling ligand and receptor complexes back to the upper surface of the cell. The juxtanuclear compartment is part of a longer circuit that routes some receptors to the basal surface and others, along with ligand, to the lysosome.     

Embryonic development and evolutionary origin of the Orthopteran auditory organs

Two different types of ears characterize the order of Orthopteran insects. The auditory organs of grasshoppers and locusts (Caelifera) are located in the first abdominal segment, those of bushcrickets and crickets (Ensifera) are found in the tibiae of the prothoracic legs. Using neuron-specific antibody labelling, we describe the ontogenetic origin of these two types of auditory organs, use comparative developmental studies to identify their segmental homologs, and on the basis of homology postulate their evolutionary origin. In grasshoppers the auditory receptors develop by epithelial invagination of the body wall ectoderm in the first abdominal segment. Subsequently, at least a part of the receptor cells undergo active migration and project their out-growing axons onto the next anterior intersegmental nerve. During this time the receptor cells and their axons express the cell-cell adhesion molecule, Fasciclin I. Similar cellular and molecular differentiation processes in neighboring segments give rise to serially homologous sensory organs, the pleural chordotonal organs in the pregenital abdominal segments, and the wing-hinge chordotonal organs in the thoracic segments. In more primitive earless grasshoppers pleural chordotonal organs are found in place of auditory organs in the first abdominal segment. In bushcrickets the auditory receptors develop in association with the prothoracic subgenual organ from a common developmental precursor. The auditory receptor neurons in these insects are homologous to identified mechanoreceptors in the meso- and metathoracic legs. The established intra- and interspecies homologies provide insight into the evolution of the auditory organs of Orthopterans.     

Characterization of two duplicate zebrafish Cb2-like cannabinoid receptors

Several cannabinoid receptors have been detected in many organisms. The best known are CB1, mainly expressed in the central nervous system and CB2 which is almost exclusively expressed in the periphery. Here we report the molecular characterization of two duplicate CB2-like cannabinoid receptors from zebrafish (Danio rerio) (zebrafish Cb2a and zebrafish Cb2b). The amino acid sequences of these receptors present 56% identity with Takifugu rubripes CB2 sequence and 39% with human CB2 sequence and conserve some specific key residues for cannabinoid receptor function. Both duplicate receptors are expressed in peripheral tissues (gills, heart, intestine and muscle), immune tissue (spleen) and also in the central nervous system. Using in situ hybridization techniques zebrafish Cb2 mRNA expression was observed for the first time in the adenohypophysial cells of the rostral pars distalis and proximal pars distalis of the pituitary gland. Given the importance of the existence of duplication of genes in teleosts, the combined analysis of these two new cannabinoid receptors opens a new exciting door to investigate and understand cannabinoid function throughout evolution.     

多巴胺D2受体在肿瘤治疗中的研究进展

多巴胺(Dopamine)(C6H3(OH)2-CH2-CH2-NH2)是人类中枢神经系统的重要儿茶酚胺类神经递质,通过其相应的膜受体而发挥情绪、饮食、运动、认知及外周血等的调节作用。多巴胺受体属于膜G蛋白偶联受体家族。目前发现的多巴胺受体有五种,其中D2受体基因主要分布于脑部。近年来的研究表明,多巴胺D2受体对肿瘤细胞具有抑制作用,对肿瘤的药物治疗具有重要意义。目前,D2受体激动剂已经成为大多数泌乳素瘤的首选治疗药物。本文通过文献回顾,对多巴胺受体在肿瘤的预后和治疗中的作用进行综述。     

腺苷A2A受体在小鼠颅脑创伤与外周组织损伤模型中的作用差异

本文旨在探索腺苷A2A受体在颅脑创伤、皮肤创伤及放射损伤复合创伤中的作用差异.分别观察和检测野生型小鼠、A2A受体基因敲除小鼠以及给予A2A受体激动剂CGS21680治疗的小鼠在皮肤创伤、放射损伤复合创伤后的伤口愈合时间以及颅脑创伤后的神经功能缺损情况、伤侧皮层脑含水量、脑脊液中谷氨酸浓度.结果表明,CGS21680促进外周组织伤口愈合,却加重颅脑创伤模型的神经功能损害,这与其促进谷氨酸释放有关.相反,A2A受体基因敲除显著延迟小鼠皮肤创伤及放射损伤复合创伤模型的伤口愈合,而在颅脑创伤模型中通过抑制谷氨酸释放产生保护效应.本研究初步证实,A2A受体激活促进谷氨酸大量释放可能是其在中枢损伤与外周损伤产生作用差异的机理之一,这为将来临床应用A2A受体激动剂减轻外周损伤,而用A2A受体拈抗剂减轻颅脑损伤提供了一定的实验依据.     

Spatial organization of tettigoniid auditory receptors: Insights from neuronal tracing

The auditory sense organ of Tettigoniidae (Insecta, Orthoptera) is located in the foreleg tibia and consists of scolopidial sensilla which form a row termed crista acustica. The crista acustica is associated with the tympana and the auditory trachea. This ear is a highly ordered, tonotopic sensory system. As the neuroanatomy of the crista acustica has been documented for several species, the most distal somata and dendrites of receptor neurons have occasionally been described as forming an alternating or double row. We investigate the spatial arrangement of receptor cell bodies and dendrites by retrograde tracing with cobalt chloride solution. In six tettigoniid species studied, distal receptor neurons are consistently arranged in double‐rows of somata rather than a linear sequence. This arrangement of neurons is shown to affect 30–50% of the overall auditory receptors. No strict correlation of somata positions between the anterio‐posterior and dorso‐ventral axis was evident within the distal crista acustica. Dendrites of distal receptors occasionally also occur in a double row or are even massed without clear order. Thus, a substantial part of auditory receptors can deviate from a strictly straight organization into a more complex morphology. The linear organization of dendrites is not a morphological criterion that allows hearing organs to be distinguished from nonhearing sense organs serially homologous to ears in all species. Both the crowded arrangement of receptor somata and dendrites may result from functional constraints relating to frequency discrimination, or from developmental constraints of auditory morphogenesis in postembryonic development. J. Morphol. © 2012 Wiley Periodicals, Inc.     

Identification of high- and low-affinity NGF receptors during development of the chicken central nervous system

In order to study regulation of the nerve growth factor (NGF) receptor during embryogenesis in chick brain, we have used affinity crosslinking of tissues with 125I-NGF. NGF interacts with high- and low-affinity receptors; high-affinity receptors are required for the majority of NGF's actions. Most measurements of receptor levels do not distinguish between high- and low-affinity forms of the receptor. We have used the lipophilic crosslinking agent HSAB to identify the high-affinity, functional receptor during development of the chicken central nervous system. A peak of expression during Embryonic Days 5-10 was detected in all regions of the chicken central nervous system, but, shortly after birth, only the cerebellar region displays significant levels of NGF receptor protein. The time course of expression confirms the dramatic regulation of the NGF receptor gene during defined embryonic periods. The detection of high-affinity NGF receptors in brain and neural retina provides strong evidence that NGF is involved in essential ontogenetic events in the development of the chicken central nervous system.     

Members of a nicotinic acetylcholine receptor gene family are expressed in different regions of the mammalian central nervous system

Nicotinic acetylcholine receptors found in the peripheral and central nervous system differ from those found at the neuromuscular junction. Recently we isolated a cDNA clone encoding the alpha subunit of a neuronal acetylcholine receptor expressed in both the peripheral and central nervous system. In this paper we report the isolation of a cDNA encoding the alpha subunit of a second acetylcholine receptor expressed in the central nervous system. Thus it is clear that there is a family of genes coding for proteins with sequence and structural homology to the alpha subunit of the muscle nicotinic acetylcholine receptor. Members of this gene family are expressed in different regions of the central nervous system and, presumably, code for subtypes of the nicotinic acetylcholine receptor.     

Evidence for the presence of CB1 cannabinoid receptors on peripheral neurones and for the existence of neuronal non-CB1 cannabinoid receptors.

The discovery of CB1 and CB2 receptors and of endogenous agonists for these receptors has sparked renewed interest in the therapeutic potential of cannabinoids. This has led to a need for strategies that will provide a better separation of wanted from unwanted effects, particularly for CB1 receptor agonists. Possible strategies are to target CB1 receptors present on neurones outside the central nervous system or novel types or subtypes of neuronal cannabinoid receptor. This paper reviews evidence for the presence of CB1 receptors on peripheral neurones and for the existence of neuronal non-CB1 cannabinoid receptors.     

Generation and pharmacological analysis of M2 and M4 muscarinic receptor knockout mice

Muscarinic acetylcholine receptors (M1-M5) play important roles in the modulation of many key functions of the central and peripheral nervous system. To explore the physiological roles of the two Gi-coupled muscarinic receptors, we disrupted the M2 and M4 receptor genes in mice by using a gene targeting strategy. Pharmacological and behavioral analysis of the resulting mutant mice showed that the M2 receptor subtype is critically involved in mediating three of the most striking central muscarinic effects, tremor, hypothermia, and analgesia. These studies also indicated that M4 receptors are not critically involved in these central muscarinic responses. However, M4 receptor-deficient mice showed an increase in basal locomotor activity and greatly enhanced locomotor responses following drug-induced activation of D1 dopamine receptors. This observation is consistent with the concept that M4 receptors exert inhibitory control over D1 receptor-mediated locomotor stimulation, probably at the level of striatal projection neurons where the two receptors are known to be coexpressed. These findings emphasize the usefulness of gene targeting approaches to shed light on the physiological and pathophysiological roles of the individual muscarinic receptor subtypes.     

Regeneration of the projection and synaptic connections of tympanic receptor fibers of Locusta migratoria (Orthoptera) after axotomy

The tergite nerve N6 of the first abdominal segment of the locust Locusta migratoria contains receptor fibers, from the tympanic organ, and hair sensilla as well as motoric axons. The nerve was axotomized in nymphal instars or adults, and the regeneration of nerve fibers was studied. The sensory fibers regrow and regenerate their projection pattern within the central nervous system. They recognize their specific neuropile areas even after entering the ganglion through different pathways. The receptor fibers of the tympanic organ reestablish synaptic connections to auditory interneurons, even though the physiological characteristics of the interneurons are not fully restored. This regenerative capability contrasts with the lack of regeneration of peripheral structures in locusts, but supports the described plasticity in the auditory system of monaural locusts (Lakes, Kalmring, and Engelhard, 1990). The motor fibers do not regenerate nerves innervating muscles of the body wall.     

Unrestrained nociceptive response and disregulation of hearing ability in mice lacking the nociceptin/orphaninFQ receptor.

In the G-protein-coupled receptor superfamily, the opioid receptor subfamily is constituted of the three distinct opioid receptors (namely delta-, mu- and kappa-subtypes) and the receptor for nociceptin (also designated orphaninFQ). The members of the opioid receptor subfamily were known to mediate a variety of cellular inhibitory effects. The three opioid receptors are known to play central roles in mediating analgesia and many other physiological activities; however, the nociceptin receptor was identified recently and less is known about its physiological roles. Here we report the generation and characterization of mice lacking the nociceptin receptor. The knockout mice showed no significant differences in nociceptive threshold and locomotor activity compared with control mice, but they lost nociceptin-induced behavioral responses. These results indicate that the nociceptin system is not essential for regulation of nociception or locomotor activity. On the other hand, we found insufficient recovery of hearing ability from the adaptation to sound exposure in the mutant mice. Thus, the nociceptin system appears to participate in the regulation of the auditory system.     

Central and peripheral alpha adrenergic activity of imidazoline derivatives

Intravenous injection of a number of imidazoline derivatives into rats induced an increase in blood pressure due to peripheral alpha adrenergic receptor stimulation. Some of these compounds, however, caused a secondary, long lasting decrease which was caused by central nervous system alpha adrenergic receptor stimulation. This central hypotensive action was only observed in the case of 2-amino-imidazolines such as clonidine, tramazoline and St 600, a clonidine analogue. Imidazolines lacking the nitrogen between the imidazoline and the benzene or naphtalene group such as oxymetazoline, xylometazoline and naphazoline were found to exert no central hypotensive action.Within the series of 2-amino-imidazolines lipid solubility turned out to be a major factor in the potency of a drug's central hypotensive action.Oxymetazoline — peripherally a very potent alpha adrenergic receptor stimulating agent — did not even cause hypotension when injected into the anterior hypothalamus, a brain structure where alpha adrenergic receptors mediating depressor effects have been localized. These data show that the hypothalamic alpha adrenergic receptors differ from peripheral alpha receptors and that only imidazolines with 2-amino substitution show affinity for these central hypotensive alpha adrenergic receptors.     

The role of aquaporins in hearing function and dysfunction

The inner ear is composed by tiny and complex structures that, together with peripheral and central auditory pathways, are responsible for hearing processing. However, not only the anatomy of the cochlea, its compartments and related structures are complex. The mechanisms involved in the regulation of homeostasis in the inner ear fluid, which determines the ionic gradient necessary for hearing and balancing sensory excitability, is an intricate phenomenon that involves several molecules. Among them, Aquaporins (AQP) play a significant role in this process. AQP are part of a family of small, integral membrane proteins that regulate different processes, including bidirectional water and ionic flow in the inner ear. Changes in the expression of these proteins are essential to auditory physiology and several pathophysiological processes in the inner ear. This review focuses on the role of AQP in health and disease of the auditory system.