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1.
Studies of hearing thresholds and frequency- and intensity-difference limens for birds are reviewed. Where possible these are related to limitations placed on auditory function by stimulus processing at peripheral levels of the avian auditory system. The high frequency limit of bird hearing is about 10 kHz; this limit is shown to be imposed in part by middle ear function and in part by cochlear mechanisms. For frequencies greater than 1.0 kHz, frequency-difference limens (DLs) show a similar dependence on frequency in birds as in mammals. Correspondingly, cochlear filtering is shown to be as good in birds as in mammals. At frequency below 1.0 kHz, frequency DLs in birds are poorer than in mammals. These low frequency differences may not be attributable to peripheral processing. Intensity-difference limens are worse in birds than mammals; there seem to be no differences in peripheral processing between birds and mammals which can account for this behavioral difference. Finally, complexities in processing at higher levels of the avian auditory system which have been related to detection of species-specific vocalizations are shown to appear in the first brainstem auditory nuclei.  相似文献   

2.
Chloride homeostasis is a critical determinant of the strength and robustness of inhibition mediated by GABA(A) receptors (GABA(A)Rs). The impact of changes in steady state Cl(-) gradient is relatively straightforward to understand, but how dynamic interplay between Cl(-) influx, diffusion, extrusion and interaction with other ion species affects synaptic signaling remains uncertain. Here we used electrodiffusion modeling to investigate the nonlinear interactions between these processes. Results demonstrate that diffusion is crucial for redistributing intracellular Cl(-) load on a fast time scale, whereas Cl(-)extrusion controls steady state levels. Interaction between diffusion and extrusion can result in a somato-dendritic Cl(-) gradient even when KCC2 is distributed uniformly across the cell. Reducing KCC2 activity led to decreased efficacy of GABA(A)R-mediated inhibition, but increasing GABA(A)R input failed to fully compensate for this form of disinhibition because of activity-dependent accumulation of Cl(-). Furthermore, if spiking persisted despite the presence of GABA(A)R input, Cl(-) accumulation became accelerated because of the large Cl(-) driving force that occurs during spikes. The resulting positive feedback loop caused catastrophic failure of inhibition. Simulations also revealed other feedback loops, such as competition between Cl(-) and pH regulation. Several model predictions were tested and confirmed by [Cl(-)](i) imaging experiments. Our study has thus uncovered how Cl(-) regulation depends on a multiplicity of dynamically interacting mechanisms. Furthermore, the model revealed that enhancing KCC2 activity beyond normal levels did not negatively impact firing frequency or cause overt extracellular K(-) accumulation, demonstrating that enhancing KCC2 activity is a valid strategy for therapeutic intervention.  相似文献   

3.
Features of sounds such as time and intensity are important binaural cues for localizing their sources. Interaural time differences (ITDs) and interaural level differences are extracted and processed in parallel by separate pathways in the brainstem auditory nuclei. ITD cues are small, particularly in small-headed animals, and processing of these cues is optimized by both morphological and physiological specializations. Moreover, recent observations in mammals and in some birds indicate that interaural time and level cues are not processed independently but cooperatively to improve the detection of interaural differences. This review will specifically summarize what is known about how inhibitory circuits improve the measurements of ITD in a sound-level-dependent manner.  相似文献   

4.
gamma-Aminobutyric acid(A) neurotransmission and cerebral ischemia   总被引:6,自引:0,他引:6  
In this review, we present evidence for the role of gamma-aminobutyric acid (GABA) neurotransmission in cerebral ischemia-induced neuronal death. While glutamate neurotransmission has received widespread attention in this area of study, relatively few investigators have focused on the ischemia-induced alterations in inhibitory neurotransmission. We present a review of the effects of cerebral ischemia on pre and postsynaptic targets within the GABAergic synapse. Both in vitro and in vivo models of ischemia have been used to measure changes in GABA synthesis, release, reuptake, GABA(A) receptor expression and activity. Cellular events generated by ischemia that have been shown to alter GABA neurotransmission include changes in the Cl(-) gradient, reduction in ATP, increase in intracellular Ca(2+), generation of reactive oxygen species, and accumulation of arachidonic acid and eicosanoids. Neuroprotective strategies to increase GABA neurotransmission target both sides of the synapse as well, by preventing GABA reuptake and metabolism and increasing GABA(A) receptor activity with agonists and allosteric modulators. Some of these strategies are quite efficacious in animal models of cerebral ischemia, with sedation as the only unwanted side-effect. Based on promising animal data, clinical trials with GABAergic drugs are in progress for specific types of stroke. This review attempts to provide an understanding of the mechanisms by which GABA neurotransmission is sensitive to cerebral ischemia. Furthermore, we discuss how dysfunction of GABA neurotransmission may contribute to neuronal death and how neuronal death can be prevented by GABAergic drugs.  相似文献   

5.
During development of inhibitory synapses, the action of the two neurotransmitters GABA and glycine shifts from depolarizing to hyperpolarizing. The shift is due to an age-dependent regulation of the intracellular free chloride concentration ([Cl(-)](i)) in postsynaptic neurons. A model system to study this maturation process is a glycinergic projection in the mammalian auditory brainstem. It is formed in the superior olivary complex (SOC) by neurons of the medial nucleus of the trapezoid body, whose axons terminate in the lateral superior olive (LSO). LSO neurons of perinatal rats and mice are depolarized upon glycine application, whereas older cells (>postnatal day (P) 8) are hyperpolarized. Here we examined the expression of six secondary active chloride transporter genes ( NCC, NKCC2, KCC1, KCC3, KCC4, and AE3) in the rat SOC to unravel the molecular mechanisms underlying this change. RT-PCR analysis demonstrated brainstem expression of KCC1, KCC3, KCC4, and AE3, but not of NCC and NKCC2. RNA in situ hybridization showed that only AE3 is highly expressed both at P3 (high [Cl(-)](i)) and P12 (low [Cl(-)](i)) in LSO neurons. KCC1 and KCC4 are weakly expressed in LSO neurons at P3 and P12, respectively. This study completes the expression analysis of all known chloride transporters sensitive to loop diuretic drugs in the SOC and demonstrates differences in the maturation between hippocampal and brainstem inhibitory synapses.  相似文献   

6.
Of the major vertebrate taxa, Class Aves is the most extensively studied in relation to the evolution of social systems and behavior, largely because birds exhibit an incomparable balance of tractability, diversity, and cognitive complexity. In addition, like humans, most bird species are socially monogamous, exhibit biparental care, and conduct most of their social interactions through auditory and visual modalities. These qualities make birds attractive as research subjects, and also make them valuable for comparative studies of neuroendocrine mechanisms. This value has become increasingly apparent as more and more evidence shows that social behavior circuits of the basal forebrain and midbrain are deeply conserved (from an evolutionary perspective), and particularly similar in birds and mammals. Among the strongest similarities are the basic structures and functions of avian and mammalian nonapeptide systems, which include mesotocin (MT) and arginine vasotocin (VT) systems in birds, and the homologous oxytocin (OT) and vasopressin (VP) systems, respectively, in mammals. We here summarize these basic properties, and then describe a research program that has leveraged the social diversity of estrildid finches to gain insights into the nonapeptide mechanisms of grouping, a behavioral dimension that is not experimentally tractable in most other taxa. These studies have used five monogamous, biparental finch species that exhibit group sizes ranging from territorial male-female pairs to large flocks containing hundreds or thousands of birds. The results provide novel insights into the history of nonapeptide functions in amniote vertebrates, and yield remarkable clarity on the nonapeptide biology of dinosaurs and ancient mammals. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.  相似文献   

7.
Scratching relieves itch, but the underlying neural mechanisms are poorly understood. We presently investigated a role for the inhibitory neurotransmitters GABA and glycine in scratch-evoked inhibition of spinal itch-signaling neurons in a mouse model of chronic dry skin itch. Superficial dorsal horn neurons ipsilateral to hindpaw dry skin treatment exhibited a high level of spontaneous firing that was significantly attenuated by cutaneous scratching, pinch and noxious heat. Scratch-evoked inhibition was nearly abolished by spinal delivery of the glycine antagonist, strychnine, and was markedly attenuated by respective GABA(A) and GABA(B) antagonists bicuculline and saclofen. Scratch-evoked inhibition was also significantly attenuated (but not abolished) by interruption of the upper cervical spinal cord, indicating the involvement of both segmental and suprasegmental circuits that engage glycine- and GABA-mediated inhibition of spinal itch-signaling neurons by noxious counterstimuli.  相似文献   

8.
Using histochemical and immunohistochemical techniques, distribution of activity of oxidative mitochondrial enzyme cytochrome oxidase (CO) and calcium-binding proteins-immunoreactivity was studied in the spiral ganglion and auditory nuclei of brainstem in two turtle species. Calbindin-, parvalbumin-and calretinin-immunoreactivity in neurons and neuropil of cochlear, supraolivary complexes, the lateral lemniscal nucleus and neuropil of spiral ganglion is shown to coincide topographically with high activity of CO. Similarity of the studied metabolic and neuro-chemical characteristics of these auditory centers in reptiles, birds and mammals suggests some general principles of their organization in amniotes, despite phylogenetic differences and peculiarities of auditory system in different species.  相似文献   

9.
Effect of ammonia on GABA uptake and release in cultured astrocytes   总被引:3,自引:0,他引:3  
While the pathogenesis of hepatic encephalopathy (HE) is unclear, there is evidence of enhanced GABAergic neurotransmission in this condition. Ammonia is believed to play a major pathogenetic role in HE. To determine whether ammonia might contribute to abnormalities in GABAergic neurotransmission, its effects on GABA uptake and release were studied in cultured astrocytes, cells that appear to be targets of ammonia neurotoxicity. Acutely, ammonium chloride (5 mM) inhibited GABA uptake by 30%, and by 50-60% after 4-day treatment. GABA uptake inhibition was associated with a predominant decrease in Vmax; the Km was also decreased. Ammonia also enhanced GABA release after 4-day treatment, although such release was initially inhibited. These effects of ammonia (inhibition of GABA uptake and enhanced GABA release) may elevate extracellular levels of GABA and contribute to a dysfunction of GABAergic neurotransmission in HE and other hyperammonemic states.  相似文献   

10.
The accumulation of reactive oxygen species during cellular injury leads to oxidative stress. This can have profound effects on ionic homeostasis and neuronal transmission. Gamma-aminobutyric acid (GABA) neurotransmission is sensitive to reactive oxygen species, but most studies have indicated that this is due to alterations in GABA release. Here, we determined whether reactive oxygen species can alter GABA(A) receptor-gated Cl- channels in the adult hippocampus. First, we measured the effects of hydrogen peroxide on intracellular Cl- using UV laser scanning confocal microscopy and the Cl(-)-sensitive probe, 6-methoxy-N-ethylquinolium iodide (MEQ). Superfusion of adult rat hippocampal slices with hydrogen peroxide for 10 min decreased MEQ fluorescence (elevation in [Cl-]i) significantly in area CA1 pyramidal cell soma. Alterations in [Cl-]i were prevented by the vitamin E analog Trolox, an antioxidant that scavenges free radicals. After exposure of slices to hydrogen peroxide, the ability of the GABA agonist muscimol to increase [Cl-]i was attenuated. To determine if GABA(A) receptors were sensitive to oxidative insults, the effect of hydrogen peroxide on the binding of [35S]t-butylbicyclophosphorothionate (TBPS) to GABA-gated Cl- channels was measured using receptor autoradiography and homogenate binding assays. Hydrogen peroxide inhibited [35S]TBPS binding in a regionally selective manner, with the greatest inhibition in cerebral cortex, hippocampus and striatum, areas vulnerable to oxidative stress. Similarly, xanthine and xanthine oxidase, which generate superoxide radicals, reduced [35S]TBPS binding in these regions. The effect of hydrogen peroxide on [35S]TBPS binding was non-competitive and was prevented by Trolox and the iron chelator, deferoxamine. We conclude that reactive oxygen species may compromise GABA(A)-mediated neuronal inhibition via interaction with pre and postsynaptic sites. A reduction in GABA(A)-gated Cl- channel function during periods of oxidative stress may contribute to the development of neuronal damage.  相似文献   

11.
Summary Mammals and birds have independently developed different populations of sensory cells grouped across the width of their auditory papillae. Although in mammals there is clear evidence for disparate functions for the two hair-cell populations, the different anatomical pattern in birds has made comparisons difficult. In two species of birds, we have used single-fibre staining techniques to trace physiologically-characterized primary auditory nerve fibres to their peripheral synapses. As in mammals, acoustically-active afferent fibres of these birds innervate exclusively the neurally-lying group of hair cells in a 11 relationship, suggesting important parallels in the functional organization of the auditory papillae in these two vertebrate classes. In addition, we found a strong trend of the threshold to acoustic stimuli at the characteristic frequency across the width of the avian papilla.Abbreviations IHC inner hair cell(s) - OHC outer hair cell(s) - SHC short hair cell(s) - THC tall hair cell(s)  相似文献   

12.
Lu T  Rubio ME  Trussell LO 《Neuron》2008,57(4):524-535
The firing pattern of neurons is shaped by the convergence of excitation and inhibition, each with finely tuned magnitude and duration. In an auditory brainstem nucleus, glycinergic inhibition features fast decay kinetics, the mechanism of which is unknown. By applying glycine to native or recombinant glycine receptors, we show that response decay times are accelerated by addition of GABA, a weak partial agonist of glycine receptors. Systematic variation in agonist exposure time revealed that fast synaptic time course may be achieved with submillisecond exposures to mixtures of glycine and GABA at physiological concentrations. Accordingly, presynaptic terminals generally contained both transmitters, and depleting terminals of GABA slowed glycinergic synaptic currents. Thus, coreleased GABA accelerates glycinergic transmission by acting directly on glycine receptors, narrowing the time window for effective inhibition. Packaging both weak and strong agonists in vesicles may be a general means by which presynaptic neurons regulate the duration of postsynaptic responses.  相似文献   

13.
Gamma-aminobutyric acid receptors (GABA(A)R) are the major sites of fast inhibitory neurotransmission in the brain, and a critical determinant for the efficacy of neuronal inhibition is the number of these receptors that are expressed on the neuronal cell surface. GABA(A)Rs are heteropentamers that can be constructed from seven subunit classes with multiple members; alpha, beta, gamma(1-3), delta, epsilon(1-3), theta, and pi. Receptor assembly occurs within the endoplasmic reticulum, and it is evident that transport-competent combinations exiting this organelle can access the cell surface, whereas unassembled subunits are ubiquitinated and subject to proteasomal degradation. In a previous report the ubiquitin-like protein Plic-1 was shown to directly interact with GABA(A)Rs and promote their accumulation at the cell surface. In this study we explore the mechanisms by which Plic-1 regulates the membrane trafficking of GABA(A)Rs. Using both recombinant and neuronal preparations it was apparent that Plic-1 increased the stability of endoplasmic reticulum resident GABA(A)Rs together with an increase in the abundance of poly-ubiquitinated receptor subunits. Furthermore, Plic-1 elevated cell surface expression levels by selectively increasing their rates of membrane insertion. Thus, Plic-1 may play a significant role in regulating the strength of synaptic inhibition by increasing the stability of GABA(A)Rs within the secretory pathway and thereby promoting their insertion into the neuronal plasma membrane.  相似文献   

14.
Despite its complexity, the neural circuitry in the auditory brainstem of vertebrates displays a fascinating amount of order. How is this order established in such a precise manner during ontogeny? In this review, we will summarize evidence for both activity-independent and activity-dependent processes involved in the generation of the auditory brainstem circuitry of birds and mammals. An example of activity-independent processes is the emergence of crude topography, which, most probably, is determined by molecular markers whose expression is genetically controlled. On the other hand, neuronal activity supports cell survival, affects dendritic and axonal growth, and influences fine tuning of maps. It appears that various types of neuronal activity, namely spontaneous versus acoustically evoked, bilateral versus unilateral, uncoordinated versus patterned, play a role during different aspects of development and cooperate with the activity-independent processes to ensure the proper formation of neuronal circuitry.  相似文献   

15.
Oscillatory network activity arises from interactions between synaptic and intrinsic membrane properties of neurons. In this review, we summarize general mechanisms of synchronous neuronal oscillations. In addition, we focus on recent experimental and computational studies which suggest that activity-dependent changes of ionic environment can affect both the synaptic and intrinsic neuronal properties and influence the network behavior. GABA(A) receptor (GABA(A)R)-mediated signaling, that is based on Cl(-) and HCO(3)(-) permeability, is thought to be important for the oscillogenesis and synchronization in cortical networks. A remarkable feature of GABAergic synapses is that prolonged GABA(A)R activation may lead to switching from a hyperpolarizing to a depolarizing response. This is partly due to a positive shift of the GABA(A) R reversal potential (E(GABA)) that is generated by GABA-induced Cl(-) accumulation in neurons. Recent studies suggest that activity-dependent E(GABA) changes may have important implications for the mechanisms of gamma oscillations and seizure-like discharges. Thus, a better understanding of the impact of intracellular Cl(-) dynamics on network behavior may provide insights into the mechanisms of physiological and pathological brain rhythms. Combination of experiments and simulations is a promising approach for elucidating which properties of the time-varying ionic environment can shape the dynamics of a given circuit.  相似文献   

16.
蜡嘴,锡嘴雀和法国鹌鹑耳蜗—中脑听觉中枢的比较观察   总被引:3,自引:1,他引:2  
用辣根过氧化物酶HRP顺行标记方法表明蜡嘴(Eophona migratoria)、锡嘴(Coccothra-ustes coccothraustes)和鹌鹑(France Coturnix coturnix)脑干内听觉中枢的初级神经元位于耳蜗核(nCO,Cochlear unclei)内。较高级神经元位于中脑背外侧核(MLD,Nucleus mesen-cephalicus lateralis,pars dorsalis)。脑干内听觉传入通路始于nCO,经外侧丘系(LL,Lemni-scus lateralis)可直接投射于MLD。鸣禽鸟蜡嘴、锡嘴是对侧投射,同侧仅有个别纤维被标记,非鸣禽鹌鹑仅是对侧性投射。  相似文献   

17.
We have identified specific GABAergic-modulated behaviors in the juvenile stage of the fruit fly, Drosophila melanogaster via systemic treatment of second instar larvae with the potent GABA transport inhibitor DL-2,4-diaminobutyric acid (DABA). DABA significantly inhibited motor-controlled body wall and mouth hook contractions and impaired rollover activity and contractile responses to touch stimulation. The perturbations in locomotion and rollover activity were reminiscent of corresponding DABA-induced deficits in locomotion and the righting reflex observed in adult flies. The effects were specific to these motor-controlled behaviors, because DABA-treated larvae responded normally in olfaction and phototaxis assays. Recovery of these behaviors was achieved by cotreatment with the vertebrate GABA(A) receptor antagonist picrotoxin. Pharmacological studies performed in vitro with plasma membrane vesicles isolated from second instar larval tissues verified the presence of high-affinity, saturable GABA uptake mechanisms. GABA uptake was also detected in plasma membrane vesicles isolated from behaviorally quiescent stages. Competitive inhibition studies of [3H]-GABA uptake into plasma membrane vesicles from larval and pupal tissues with either unlabeled GABA or the transport inhibitors DABA, nipecotic acid, or valproic acid, revealed differences in affinities. GABAergic-modulation of motor behaviors is thus conserved between the larval and adult stages of Drosophila, as well as in mammals and other vertebrate species. The pharmacological studies reveal shared conservation of GABA transport mechanisms between Drosophila and mammals, and implicate the involvement of GABA and GABA transporters in regulating physiological processes distinct from neurotransmission during behaviorally quiescent stages of development.  相似文献   

18.
In vivo microdialysis and behavioural studies in the domestic chick have shown that glutamatergic as well as monoaminergic neurotransmission in the medio-rostral neostriatum/hyperstriatum ventrale (MNH) is altered after auditory filial imprinting. In the present study, using pharmaco-behavioural and in vivo microdialysis approaches, the role of dopaminergic neurotransmission in this juvenile learning event was further evaluated. The results revealed that: (i) the systemic application of the potent dopamine receptor antagonist haloperidol (7.5 mg/kg) strongly impairs auditory filial imprinting; (ii) systemic haloperidol induces a tetrodotoxin-sensitive increase of extracellular levels of the dopamine metabolite, homovanillic acid, in the MNH, whereas the levels of glutamate, taurine and the serotonin metabolite, 5-hydroxyindole-3-acetic acid, remain unchanged; (iii) haloperidol (0.01, 0.1, 1 mm) infused locally into the MNH increases glutamate, taurine and 5- hydroxyindole-3-acetic acid levels in a dose-dependent manner, whereas homovanillic acid levels remain unchanged; (iv) systemic haloperidol infusion reinforces the N-methyl-d-aspartate receptor-mediated inhibitory modulation of the dopaminergic neurotransmission within the MNH. These results indicate that the modulation of dopaminergic function and its interaction with other neurotransmitter systems in a higher associative forebrain region of the juvenile avian brain displays similar neurochemical characteristics as the adult mammalian prefrontal cortex. Furthermore, we were able to show that the pharmacological manipulation of monoaminergic regulatory mechanisms interferes with learning and memory formation, events which in a similar fashion might occur in young or adult mammals.  相似文献   

19.
Proliferation and transdifferentiaton of supporting cells in the damaged auditory organ of birds lead to robust regeneration of sensory hair cells. In contrast, regeneration of lost auditory hair cells does not occur in deafened mammals, resulting in permanent hearing loss. In spite of this failure of regeneration in mammals, we have previously shown that the perinatal mouse supporting cells harbor a latent potential for cell division. Here we show that in a subset of supporting cells marked by p75, EGFR signaling is required for proliferation, and this requirement is conserved between birds and mammals. Purified p75+ mouse supporting cells express receptors and ligands for the EGF signaling pathway, and their proliferation in culture can be blocked with the EGFR inhibitor AG1478. Similarly, in cultured chicken basilar papillae, supporting cell proliferation in response to hair cell ablation requires EGFR signaling. In addition, we show that EGFR signaling in p75+ mouse supporting cells is required for the down-regulation of the cell cycle inhibitor p27(Kip1) (CDKN1b) to enable cell cycle re-entry. Taken together, our data suggest that a conserved mechanism involving EGFR signaling governs proliferation of auditory supporting cells in birds and mammals and may represent a target for future hair cell regeneration strategies.  相似文献   

20.
Triethyllead (TEL) is a CNS neurotoxin producing bizarre neurobehavioral changes. The principal objective of this study was to determine if TEL-induced defects in energy metabolism were responsible for the inhibition of synaptosomal Na+-dependent high-affinity uptake of gamma-aminobutyric acid (GABA). A dose-dependent inhibition of GABA uptake (ID50 = 10 microM TEL) was found during 30-s incubations. Uptake of glutamate was more resistant to the inhibitory effects of TEL. A TEL-induced Cl(-)-dependent synaptosomal deficit of ATP was observed. Such deficit in high-energy phosphate was time-dependent and did not occur in the absence of Cl- or as early as 30 s. Inhibition of GABA uptake, on the other hand, was a Cl(-)-independent phenomenon and was observed at as early as 30 s. TEL was not competitive with Na+ or GABA itself, as the effects of TEL were not overcome with high [Na+] or [GABA]. These results indicate that the locus of TEL inhibition of GABA uptake is not a Cl(-)-dependent event and does not involve a perturbed transmembrane electrochemical gradient, due to either an observed mitochondrial defect or an inhibition of Na+, K+-ATPase directly.  相似文献   

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