Auditory neuroscience最新文献

Strial marginal cells (SMC) and vestibular dark cells (VDC) are known to secrete K(+) into endolymph. Slowly-activating, voltage-dependent K(+) channels (KCNQ1/KCNE1; IsK; min K) have been identified in the apical membrane of these cells. Several experimental maneuvers known to increase or decrease transepithelial K(+) secretion have been found in VDC to change the current through these channels in the same ways. In both SMC and VDC the kinetics of activation and deactivation resemble those of the I(sK) channel exogenously expressed in Xenopus oocytes and endogenous to heart myocytes. The present study sought evidence that this current is indeed carried by I(sK) channels and that this current is the basis for transepithelial K(+) secretion. Both on-cell macro-patch recordings of the apical membrane and perforated-patch whole-cell recordings were made on SMC from gerbil in order to measure macroscopic cell currents. The on-cell current was found to 1) be K(+)-selective, 2) have a cation permeability sequence of K(+) ~ Rb(+) > Cs(+) >> Li(+) = Na(+), 3) be activated with a time constant of 1764 ± 413 ms by voltage steps from 0 to +40 mV, 4) be deactivated with a time constant of 324 ± 57 ms by voltage steps from 0 to -40 mV and 5) be reduced 84 ± 5% by bumetanide (10(-5) M), an inhibitor of K(+) secretion. The single-channel conductance of the apical currents in the homologous VDC was estimated by fluctuation analysis to be 1.6 pS. The potent inhibitor of I(sK) channels, chromanol 293B (10(-5) M), reduced the whole-cell current in SMC by 72 ± 10 %. Clofilium (10(-4) M), a putative I(sK) channel inhibitor known to have additional non-specific effects, led to a stimulation of both on-cell (by 598 ± 177%) and whole-cell (by 162 ± 18%) currents in gerbil SMC but to a decrease of whole-cell currents (by 39 ± 12%) in rat SMC. Taken together with other findings reviewed here, these results strongly argue that the slowly-activating, voltage-dependent conductance in the apical membrane of SMC is the I(sK) channel and provide additional evidence for the poor specificity of clofilium.

Experiment 1 derived mathematical models for estimating the neural rate representation of changes in the second formant (F2) frequency of the vowel /ε/. Models were based on linear fits to response patterns of auditory-nerve fibers with high, medium and low spontaneous rates (SRs), as characterized in previous electrophysiological studies of anesthetized cats (Le Prell et al., 1996). Simulations were run at several vowel levels in quiet and in the presence of continuous background noise. Noise levels were adjusted to produce a constant signal-to-noise ratio (S/N) of 3 dB at each vowel level. A signal detection analysis of model outputs suggested that auditory-nerve fibers with low SR provided the best rate representation of changes in F2 frequency at higher vowel levels and in background noise. Experiment 2 examined the predictions of the auditory nerve model by measuring psychophysical thresholds for F2 frequency changes (ΔF2) in cats. Behavioral tests were performed at vowel levels of 31, 51, and 71 dB in continuous background noise at S/Ns of 3, 13, and 23 dB. ΔF2 increased with decreasing S/N at each of these three vowel levels. Trends in behavioral performance corresponded well with the quality of vowel representations that are provided by high SR auditory-nerve fibers at low vowel levels and low SR fibers at moderate-to-high levels.

Neural representations of complex vowel-like spectra have been extensively characterized by population studies of single fiber responses in the auditory nerve of anesthetized cats. With traditional population measures, neural rate responses to formants (energy peaks) and troughs (energy minima) in a vowel's amplitude spectrum are measured by sampling several fibers, each tuned to one spectral feature. Similar analyses are rarely performed on structures in the central auditory system primarily due to the difficulty of obtaining the samples of neurons that are needed to construct complete population response profiles. As an alternative to population measures, this study introduces a method for estimating population measures from the responses of individual auditory-nerve fibers. With our spectrum manipulation procedure (SMP), a response profile was created by sampling the responses of individual fibers as important spectral features were shifted to the units' best frequency (BF, the frequency to which a neuron is most sensitive). Observed SMP rate profiles showed the same effects of rate saturation, two-tone suppression, and spontaneous rate as population measures. In addition, when analyzed with signal detection methods, changes in rate responses within individual neurons revealed new insights into how the neural representation of vowel stimuli may be influenced by unit threshold and best frequency. SMP sampling techniques should prove useful in future studies of speech encoding in the central auditory system.

The cochlear nucleus (CN) receives cholinergic inputs primarily from centrifugal pathways. There is evidence that the effects of these cholinergic inputs may be mediated mainly by muscarinic acetylcholine receptors. We used 1-[N-methyl-³H]scopolamine (NMS) to study muscarinic receptor binding in the rat CN autoradiographically. To determine which muscarinic receptor subtypes participate in the binding, we included competition assays using the unlabeled subtype-preferential ligands pirenzepine, AF-DX 116, 4-DAMP, HHSiD, and tropicamide to compete with [³H]NMS for binding. Our results suggest that NMS binding density in the CN is about a tenth of that in the facial nucleus. Inside the CN, the highest binding was found in granular regions, followed in order by the dorsal CN (DCN) fusiform soma layer, the DCN molecular layer, the DCN deep layer, the anteroventral CN (AVCN) and posteroventral CN (PVCN). Binding in the interstitial nucleus (auditory nerve root) was similar to background. The results of the competition assays suggest that the M₂ receptor subtype predominates in VCN, M₄ in the DCN fusiform soma layer, and both subtypes in DCN molecular and deep layers. M₄ and M₃ subtypes predominated in the granular region of AVCN, while M₁ and M₂ were more prominent in the granular region of PVCN. The results show similarities to those obtained with pharmacological and immunohistochemical methods, but also some discrepancies. The different distributions of the different muscarinic receptor subtypes suggest that the effects of cholinergic inputs may differ among CN subregions, in agreement with in vivo pharmacological results. Overall, the centrifugal cholinergic influences on information processing in the CN may especially involve M₂ and M₄ receptors.

The purpose of this study was to test the effects of intense tone exposure on the spontaneous activity of multiunit clusters in the mammalian dorsal cochlear nucleus (DCN). Adult hamsters (60-101 days of age) were exposed to a 10 kHz tone at levels between 125 and 130 dB SPL for a period of 4 hours. The effects of tone exposure were studied following a recovery period of 30-58 days and were quantified by measuring the spontaneous rates, response thresholds and frequency tuning properties of neural clusters at the surface of the DCN. Measures were performed at each of 10-15 sites along the tonotopic axis of the DCN. The effects of the tone exposure were examined by comparison with identical measures obtained from normal unexposed animals. Results indicate that tone exposure induced major chronic increases in the spontaneous activity of the DCN. Such increases were broadly distributed across the tonotopic range of the DCN and were generally found in tonotopic map areas characterized by tone-induced elevations of neural thresholds. Mean spontaneous rate reached its maximum value at or close to the tonotopic locus which normally represents the frequency of the exposure tone. The increased activity induced by tone exposure resembled the heightened activity in normal animals during presentation of a moderate level continuous tone. These changes in spontaneous activity indicate that central auditory neurons are in a state of elevated activity for extended periods following intense sound exposure and suggest that the affected neurons may signal the presence of acoustic stimulation even though such stimulation is not present. Possible mechanisms of these changes and their relation to the clinical problem of tinnitus are discussed.

Behavioral experiments examined the effects of olivocochlear efferent lesions on performance in an intensity discrimination task. Five cats were trained with food reinforcement to signal the detection of a change in the intensity of pure tones by releasing a response lever. Intensity cues were conveyed by 1 and 8-kHz tone bursts in quiet and in the presence of continuous broadband noise. After the collection of baseline behavioral data, the olivocochlear bundle (OCB) was sectioned with bilateral knife cuts on the floor of the IVth ventricle. The completeness of OCB lesions was evaluated at the conclusion of post-lesion behavioral testing by light microscopic examination of cochlear acetylcholinesterase staining and electrophysiological measures of contralateral noise suppression of compound action potentials (CAPs). Cats with OCB lesions showed greatest performance deficits for the discrimination of 8-kHz intensity changes in continuous background noise. The subjects' ability to discriminate 1-kHz intensity changes in noise was poor prior to OCB lesioning and did not change after the surgical procedure. Lesioning effects were not observed at either frequency when tests were conducted in quiet. These results suggest that olivocochlear feedback contributes to the auditory processing of mid-frequency acoustic signals in noisy backgrounds.

Purinergic receptors have been found to modulate ion transport in several types of epithelial cells as well as excitable cells. It was of interest to determine whether vestibular dark cells and strial marginal cells contain purinergic receptors in either the apicalor basolateral membrane which modulate transepithelial ion transport. Vestibular dark cell and strial marginal cell epithelia were mounted in a micro-Ussing chamber for the measurement of the transepithelial voltage and resistance from which the equivalent short circuit current (I(sc)) was obtained. The apical and basolateral sides were independently perfused with adenosine and adenosine 5'-triphosphate (ATP). Adenosine (10(-5) M) had no effect on I(sc) at either the apical or basolateral side of vestibular dark cells and strial marginal cells, suggesting either the absence of P(1) receptors or the absence of coupling of P(1) receptors to vectorial ion transport by these epithelia. Apical perfusion of ATP (10(-8) to 10(-4) M) caused a decrease in I(sc) of both vestibular dark cells and strial marginal cells. Apical perfusion of the nucleotides uridine 5'-triphosphate (UTP), 2-methylthioadenosine triphosphate (2-meS-ATP), adenosine 5'-O-(3-thiotriphosphate) (ATPγS) and α,β-methylene adenosine 5'-triphosphate (α,β-meth-ATP) caused qualitatively similar responses with different magnitudes of response. The sequence of the magnitude of response of each compound at 10(-6) or 10(-5) M was assessed from the fractional change of I(sc). The sequence for vestibular dark cells was UTP = ATP = ATPγS ≫ 2-meS-ATP > α,β-meth-ATP, and for strial marginal cells it was UTP = ATP ≫ 2-meS-ATP, corresponding to the sequence for the P(2U) receptor. The effect of agonist on the apical membrane was reduced by the antagonist 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) but not cibacron blue or suramin. DIDS in the absence of exogenous purinergic agonist caused a sustained increase in I(sc). The effect of ATP on the apical membrane was greater in the absence of divalent cations. Basolateral perfusion of ATP led to a biphasic response of I(sc) in vestibular dark cell and strial marginal cell epithelia, consisting of an initial rapid increase followed by a slower decrease. Perfusion of the perilymphatic surface of the stria vascularis (basal cell layer) with ATP had no acute effect on I(sc). The initial increase of I(sc) in vestibular dark cell epithelium during basolateral perfusion had a sequence of 2-meS-ATP > ATP ≫ UTP = α,β-meth-ATP = ATPγS, corresponding to the sequence for the P(2Y) receptor. Subsequently, the agonists caused a sustained decrease in I(sc) with a sequence of ATPγS > 2-meS-ATP > ATP > UTP >α,β-meth-ATP. This sequence is most simply interpreted as the result of the coexistence of P(2U) and P(2Y) receptors in the basolateral membrane. Both the increase and decrease of I(sc) by ATP at the basolateral membrane were reduced by the antagonist suramin. These findings provide eviden