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1.
付子英曾红唐佳李洁李娟陈其才 《生理学报》2013,(3):329-337
细胞外记录研究报道听中枢神经元的调制方向选择性和前掩蔽均与神经抑制有关,但由于未能获得抑制性突触输入作用的直接证据,尚存有争议。本研究在20只昆明小鼠(Mus musculus Km)上进行在体细胞内记录,研究了下丘神经元调频声的调制方向选择性或偏好与其前掩蔽之间的关系。共获得93个下丘神经元,对其中37个产生动作电位(action potential,AP)发放且数据完整的神经元做了分析和讨论。在上扫选择性神经元(n=12)频率调谐的高频边存在抑制性突触后电位构成的抑制区,而在下扫选择性神经元(n=8)的低频边存在抑制区,在不具有调制方向选择性的神经元(n=17)频率调谐的高、低频边均未观察到有明显的抑制区,表明这些抑制区是调频声调制方向选择性形成的重要原因。比较上扫和下扫调频声对上、下扫选择性和非选择性神经元的前掩蔽效应,结果显示具有调制方向选择性的神经元,其所偏好方向的调频声对最佳频率(best frequency,BF)声产生的前掩蔽强于非偏好的调频声;而无调制方向选择性神经元,上、下扫调频声的掩蔽效应无差异。以上结果提示,AP后跟随的强抑制性突触后电位可能是调制方向选择性神经元前掩蔽产生的机制。 相似文献
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持续与间断噪声前掩蔽条件下小鼠下丘神经元的不同反应模式 总被引:4,自引:0,他引:4
有关听中枢神经元纯音前掩蔽效应的神经表征已进行了大量研究,但是,噪声前掩蔽尤其是间断噪声前掩蔽效应的神经表征却鲜有报道。本研究观察了自由声场条件下,昆明小鼠下丘神经元在持续与间断噪声前掩蔽条件下对纯音探测声的反应。共记录到96个下丘神经元,测量了其中51个神经元在不同声刺激条件下的强度一放电率函数。结果显示,掩蔽声强度分布较广(探测声阈下21dB至阈上19dB之间)。在将近一半的神经元中,间断噪声的前掩蔽效应比持续噪声强(Ⅰ型,45.10%,P〈0.001),但也有少数神经元其间断噪声的掩蔽效应较持续噪声的弱(Ⅲ型,17.65%,P〈0.001),部分神经元无显著性差异(Ⅱ型,37.25%,P〉0.05)。无论Ⅰ型还是Ⅲ型神经元,持续噪声和间断噪声均在探测声强度较低时产生较强的抑制效应,随着探测声强度的升高,抑制效应逐渐降低(P〈0.001);同时,持续噪声和间断噪声之间前掩蔽效应差异亦不复存在(P〉0.05)。此外,当掩蔽声由持续噪声换为间断噪声后,部分Ⅰ型神经元掩蔽时相的类型发生转变,其中最主要的转变为由前期抑制转变为均衡抑制(53.85%,7/13)。对下丘神经元声反应的时间域以及强度域,持续与间断噪声具有分化性前掩蔽效应,提示噪声前掩蔽并非简单的神经元发放压抑源,某些主动性神经调制机制可能参与了噪声条件下时相声信息的编码过程。 相似文献
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自由声场条件下,通过给予小鼠具有不同时程(10、40及100ms)、强度(最小阈值以上5、15、25、35及45dBSPL)、呈现率(0.5、1、2、3.3、5、6.7、10和20Hz)的纯音短声刺激,分析探讨了昆明小鼠下丘神经元声刺激跟随力与声时程及强度的关系。结果发现:多数神经元的脉冲发放数随声强增高而增加,随短声时程的延长而减少;随声强的增高,多数神经元的临界呈现率(CPR)和最大呈现率(MPR)变大,而随短声时程的延长,神经元的CPR、MPR变小为主要趋势;下丘神经元的声反应跟随力总体上随时程延长而下降,随声强加大而提高。推测当声时程延长、强度下降时,前次刺激对后继刺激声反应的抑制性影响增强,提示声时程适当缩短、声强增大可能有助于下丘神经元汇聚更多的声信息进行高级神经处理,从而提高听中枢表征高密度声信息的能力。 相似文献
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以回声定位蝙蝠为模式动物,采用在体动物细胞外单位记录法,研究了后掩蔽效应对下丘神经元声反应的影响。结果显示,部分神经元(38%,12/31)对测试声刺激的反应明显受到掩蔽声的抑制,其后掩蔽效应强弱与掩蔽声和测试声的相对强度差(inter-stimulus level difference,SLD),以及测试声与掩蔽声之间的间隔时间(inter-stimulus onset asynchrony,SOA)有关:当掩蔽声强度升高或测试声强度降低时,后掩蔽效应增强;而SOA的缩短,亦可见后掩蔽效应增强。另外,相当数量的神经元(52%,16/31)对测试声刺激的反应并不受掩蔽声的影响,其中有的神经元只有在特定SLD和SOA时,才表现出后掩蔽效应。而少数下丘神经元(10%,3/31)在特定SLD和SOA时,掩蔽声对测试声反应有易化作用。上述结果表明,部分下丘神经元参与了声认知活动中的后掩蔽形成过程,推测下丘神经元在定型声反应特性中,对掩蔽声诱导的兴奋前抑制性输入与测试声诱导的兴奋性输入之间的时相性动态整合起关键作用。 相似文献
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为探讨下丘(Inferior colliculus,IC)回声定位信号主频范围内的神经元的时程选择性,在自由声场刺激条件下,我们在4 只普氏蹄蝠的IC 采用不同时程的声刺激,研究了神经元的时程选择性。通过在体细胞外记录,共获得56 个声敏感下丘神经元,其记录深度、最佳频率和最小阈值的范围分别为1547 - 3967 (2878. 9 ±629.1)μm,20 -68 (49.0 ± 11. 1)kHz 和36.5 -95. 5 (59. 8 ±13. 0)dB SPL。根据所记录到的下丘神经元对不同时程的声刺激的反应,即对不同时程的选择性(Duration selectivity),将其分为6 种类型:短通型(Short-pass,SP,n = 11/56)、带通型(Band-pass,BP,n = 1/56)、长通型(Long-pass,LP,n = 5 /56)、反带通型(Band-reject,BR,n = 3 /56)、多峰型(Multi-peak,MP,n =6 /56)和全通型(All-pass,AP,n =30 /56)或非时程选择型(Nonduration-selective,NDS)。通过比较普氏蹄蝠下丘谐波主频内和主频外神经元的时程选择性,我们发现处于回声定位信号主频范围内神经元(n =32)比主频外神经元(n = 24)具有更短的最佳时程和更高的时程选择性。结果提示,在普氏蹄蝠回声定位过程中谐波主频内神经元较谐波主频外神经元发挥了更为重要的作用。 相似文献
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昆明小鼠下丘神经元对调频声的反应 总被引:1,自引:0,他引:1
尽管昆明小鼠下丘神经元对纯音的反应已有深入研究,但其对调频声的反应情况却未见报道。本研究在自由声场条件下,采用单单位细胞外记录方法,观察了昆明小鼠下丘神经元对调频声刺激的反应情况。根据神经元对调频声及纯音反应的阈值差异,所记录的99个下丘神经元可分为三种类型:对调频声刺激反应的阈值低于纯音的为Ⅰ型(57/99,57.6%),二者阈值相当的为Ⅱ型(12/99,12.1%),而纯音阈值低于调频声的为Ⅲ型(30/99,30.3%)。与Ⅲ型神经元相比,Ⅰ型神经元具有较低的CF和Q20dB(P<0.05和P<0.001)和较高的RB20dB(P<0.05)。通过分析下丘神经元对上、下扫时发放数的差异,发现有36个(36/99,36.4%)神经元表现出方向选择性,其中22个(22/99,22.2%)为上扫敏感,其余14个(14/99,14.2%)为下扫敏感,且上扫敏感性神经元比下扫敏感性神经元在Ⅰ、Ⅱ和Ⅲ型神经元中有更广的分布范围。通过比较发现,Ⅰ型神经元和方向选择性神经元的特征频率都非常集中地分布在10kHz-20kHz范围内(77.2%和83.3%)。此外,对其中24个神经元采取了不同调制速度的调频声刺激,大多数(15/24,62.5%)神经元对快调频声反应最为敏感,并且随着调制速度的升高,方向选择性神经元的比例有下降趋势(45.8%vs41.7%vs33.3%)。上述结果提示,昆明小鼠下丘神经元能有效处理调频声刺激,且具有方向选择性的调频声在昆明小鼠的声通讯中占有重要地位。 相似文献
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采用自由声场的纯音短声刺激研究昆明小鼠下丘神经元听反应特征的性别差异。结果表明,①下丘神经元放电形式雌性以相位型为主,雄性以持续紧张型为主,且持续紧张型出现率存在明显的性差(P<005);②最佳频率分布雌雄都主要集中在10~20kHz,而潜伏期分布雌性较雄性集中;③最小阈值分布雌性主要集中于40~63dBSPL,而雄性无明显的集中区;④神经元最大发放雌性明显高于雄性(P<001);⑤脉冲发放函数和潜伏期函数的类型雌雄相同,但非单调型潜伏期函数出现率雄性明显高于雌性(P<001);⑥小鼠下丘神经元频率调谐曲线被分成五类,各类出现率在雌雄间无明显差异,但宽阔型频率调谐曲线百分率雌性明显高于雄性(P<005),且雌性频率调谐曲线高频边反转斜率明显高于雄性(P<005)。因此提示,雌雄小鼠下丘神经元声反应特征存在一定的差异。 相似文献
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弱噪声对小鼠下丘神经元频率调谐的影响 总被引:5,自引:1,他引:5
为探讨弱噪声对小鼠 (MusmusculusKm)中脑下丘 (inferiorcolliculus ,IC)神经元声信号提取的影响 ,采用单位胞外记录方法 ,研究了加入弱白噪声 (强度相当于纯音阈强度下 5dB)前后神经元频率调谐曲线的变化。实验共记录到 10 4个下丘神经元 ,测量了 32个神经元的频率调谐曲线。结果显示 :①弱噪声条件下神经元的频率调谐曲线表现出 3种类型 ,即锐化 (34 4 % ,11/ 32 )、拓宽 (18 8% ,6 / 32 )和不受影响 (4 6 9% ,15 / 32 ) ,其中锐化呈现有意义的变化 ;②频率调谐受弱噪声锐化的神经元 ,其Q10 、Q3 0 平均分别增大 (34 4 2±17 0 4 ) % (P =0 0 2 6 ,n =11)和 (4 6 34± 2 2 88) % (P =0 0 0 9,n =7) ,且Q3 0 变化率大于Q10 ;③弱噪声对调谐曲线的高、低频边锐化度不一 ,神经元低频边的反转斜率基本不变 [由 0 16± 0 0 8变为 0 16± 0 0 7kHz/dB (P =0 94 7,n =7) ],而高频边明显下降 [由 0 5 2± 0 2 5下降为 0 2 6± 0 13kHz/dB ,平均减小 (4 3 81±2 4 0 6 ) % ,(P =0 0 4 6 ,n =7) ]。上述结果表明 ,弱噪声可锐化小鼠IC神经元频率调谐 ,并强化神经元的声信号高频分析能力 相似文献
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自由声场条件下,采用特定双声刺激、双电极同步记录方法研究了下丘神经元的频谱整合作用。实验在6只大棕蝠(Eptesicus fuscus)上进行,共获得22对频谱整合相关的配对神经元。结果显示:(1)81.8%(36/44)的配对神经元产生相互抑制性频谱整合,18.2%(8/44)为相互易化性频谱整合;(2)频谱整合的范围主要在20~30kHz之间,其中约一半(45.5%,20/44)的配对神经元其最佳频率差小于2kHz,但也可见最佳频率差大于10kHz的配对神经元(13.6%,6/44)产生频谱整合;(3)下丘神经元的频率及强度选择性受频谱整合作用的调制。推测等频层内及等频层之间的下丘神经元在声信号处理过程中存在相互作用机制,以利于对复杂声信号的加工。 相似文献
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Neural correlates of behavioral gap detection in the inferior colliculus of the young CBA mouse 总被引:6,自引:0,他引:6
J. P. Walton R. D. Frisina J. R. Ison W. E. O'Neill 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1997,181(2):161-176
The gap detection paradigm is frequently used in psychoacoustics to characterize the temporal acuity of the auditory system. Neural responses to silent gaps embedded in white-noise carriers, were obtained from mouse inferior colliculus (IC) neurons and the results compared to behavioral estimates of gap detection. Neural correlates of gap detection were obtained from 78 single neurons located in the central nucleus of the IC. Minimal gap thresholds (MGTs) were computed from single-unit gap functions and were found to be comparable, 1–2 ms, to the behavioral gap threshold (2 ms). There was no difference in MGTs for units in which both carrier intensities were collected. Single unit responses were classified based on temporal discharge patterns to steady-state noise bursts. Onset and primary-like units had the shortest mean MGTs (2.0 ms), followed by sustained units (4.0 ms) and phasic-off units (4.2 ms). The longest MGTs were obtained for inhibitory neurons (xˉ = 14 ms). Finally, the time-course of behavioral and neurophysiological gap functions were found to be in good agreement. The results of the present study indicate the neural code necessary for behavioral gap detection is present in the temporal discharge patterns of the majority of IC neurons. Accepted: 6 February 1997 相似文献
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为了探讨γ-氨基丁酸(γ-aminobutyric acid,GABA)能抑制对大棕蝠(Eptesicus fuscus)听皮层(auditory cortex,AC)神经元声反应特性的影响,采用多管微电极电泳方法,观察了8只大棕蝠AC神经元去ABA能抑制前后声刺激诱发的反应。结果显示,微电泳GABAa受体拮抗剂荷包牡丹碱(bicuculline,Bic)去ABA能抑制可改变声刺激诱发的反应模式;极大地增加神经元冲动发放率,缩短反应的潜伏期和降低反应的最小阈值;不同程度地改变强度-发放率和强度-潜伏期函数。结果提示:1、GABA能抑制对AC神经元声信号处理起重要作用;2、GABA能抑制可改变AC神经元兴奋性支配或输入的效应,并因此定型AC神经元的声反应性质,即发放模式、阈值、强度-发放率和强度-潜伏期函数;3、GABA能抑制为AC神经元的声诱发活动提供一种调制性抑制。 相似文献
13.
To study the effects of different durations of forward masker sound on neuronal firing and rate-intensity function (RIF) of mouse inferior collicular (IC) neurons, a tone relative to 5 dB above the minimum threshold (re MT+5 dB) of the best frequency of recorded neurons was used as forward masker sound under free field stimulation condition. The masker durations used were 40, 60, 80, and 100 ms. Results showed that as masker duration was increased, inhibition in neuronal firing was enhanced (P < 0.000 1, n = 41) and the latency of neurons was lengthened (P<0.01, n = 41). In addition, among 41 inhibited IC neurons, 90.2% (37/41) exhibited narrowed dynamic range (DR) when masker sound duration was increased (P < 0.000 1), whereas the DR of 9.8%(4/41) became wider. These data suggest that masking effects of different durations of forward masker sound might be correlated with the amplitude and duration of inhibitory input to IC neurons elicited by the masker sound. __________ Translated from Journal of Central China Normal University (Nat. Sci.), 2005, 39(2): 236–240 [译自: 华中师范大学学报 (自然科学版), 2005, 39(2): 236–240] 相似文献
14.
To study the effects of different durations of forward masker sound on neuronal firing and rate-intensity function(RIF)of mouse inferior collicular(IC)neurons,a tone relative to 5 dB above the minimum threshold(re MT+5 dB)of the best frequency of recorded neurons was used as forward masker sound under free field stimulation condition.The masker durations used were 40,60,80,and 100 ms.Results showed that as masker duration was increased,inhibition in neuronal firing was enhanced(P<0.0001,n=41)and the latency of neurons was lengthened(P<0.01,n=41).In addition,among 41 inhibited IC neurons,90.2%(37/41)exhibited narrowed dynamic range(DR)when masker sound duration was increased(P<0.0001),whereas the DR of 9.8%(4/41)became wider.These data suggest that masking effects of different durations of forward masker sound might be correlated with the amplitude and duration of inhibitory input to IC neurons elicited by the masker sound. 相似文献
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直接遗忘效应中认知抑制机制研究新进展 总被引:1,自引:0,他引:1
随着认知抑制研究的兴起,作为测量认知抑制能力的主要方法,直接遗忘效应得到了不断深入的研究。本文简要介绍了直接遗忘效应的研究范式,并就直接遗忘的内在机制是"选择性复述"的作用,还是"认知抑制"的作用展开讨论。在此基础上还就个体抑制能力的发展进程及其应用价值的研究进展做了简要介绍,并指出了已有研究存在的一些问题。 相似文献
16.
Molecules in male seminal fluid transferred to female insects during mating can have potent effects on their subsequent sexual and reproductive behaviour. Like many other tephritids, female Queensland fruit flies (Bactrocera tryoni) typically have diminished sexual receptivity after their first mating. Also, copulations of females that do remate tend to be shorter than those of virgins. We here find that virgin females injected with small doses (0.1, 0.2 or 0.5 male equivalents) of extracts from the male reproductive tract accessory tissues, which consist of male accessory glands, ejaculatory apodeme and ejaculatory duct (AG/EA/ED), have diminished receptivity and short copula duration very similar to naturally mated females. In contrast, virgin females injected with saline or with high doses of AG/EA/ED (1 or 2 male equivalents) that likely exceed the range of natural variation retain the higher levels of sexual receptivity and longer copulations of un-injected virgins. We conclude that reduced sexual receptivity and shorter copulations of mated female Q-flies are mediated by products in the male seminal fluid derived from the male reproductive tract accessory tissues. 相似文献
17.
Marius Muth Niklas Jänsch Aleksandra Kopranovic Andreas Krämer Nathalie Wössner Manfred Jung Frank Kirschhöfer Gerald Brenner-Weiß Franz-Josef Meyer-Almes 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(3):577-585
Background
HDAC8 is an established target for T-cell lymphoma and childhood neuroblastoma. Benzothiazine-imines are promising HDAC8 inhibitors with unknown binding mechanism lacking a usual zinc binding group.Methods
In this study high-resolution and quantitative HPLC-coupled ESI-MS/MS techniques are combined with crystal structure determination and a variety of biochemical and computational methods to elucidate the reaction mechanism between benzothiazine-imine 1 and HDAC8.Results
1) 1 is a covalent inhibitor of HDAC8; 2) inhibition is reversible in the presence of reducing agents; 3) C153 in the active site and C102 are involved in the inhibition mechanism; 4) 1 modifies various cysteines in HDAC8 forming either thiocyanates or mixed disulfides with 3; 5) 1 and 5 dock in close proximity to C153 within the active site. This is supposed to accelerate covalent inactivation particularly in HDAC8 and suggested as major determinant for the observed nanomolar potency and selectivity of 1.Conclusions
1 and its analogs are interesting model compounds but unsuitable for therapeutic treatment due to their high unselective reactivity towards thiol groups. However, the postulated preceding non-covalent binding mode of 1 opens a door to optimized next generation compounds that combine potent and selective non-covalent recognition with low reactivity towards C153 at the active site of HDAC8.General significance
1 represents a completely new class of inhibitors for HDAC8. Initial non-covalent interaction at the bottom of the active site is suggested to be the key for its selectivity. Further optimization of non-covalent interaction and thiol-reactivity provides opportunities to develop therapeutic useful covalent HDAC8 inhibitors. 相似文献18.
The paralyzed, decerebrate frog, Rana catesbeiana, displays “fictive” oropharyngeal and pulmonary ventilations. In order to evaluate the neuronal correlates of these two centrally programmed ventilatory bursting patterns, we have performed intra-and extracellular recordings of bulbar respiratory neurons in this fictively breathing preparation. A total of 123 respiratory neurons were recorded from the caudal medulla. Of 51 antidromically activated neurons, 20 were vagal motoneurons and 31 were hypoglossal motoneurons. Respiratory neurons that depolarized during the lung (L) or non-lung (N) ventilatory phases were classified as L or N neurons, respectively. Phase spanning neurons (S) were active during both L and N phases. Some neurons showed oscillations of membrane potential synchronous with oropharyngeal ventilation. Those active during the buccal elevation phase were exclusively L neurons whereas those having buccal depressor activity were exclusively N neurons. Synaptic drive potentials were observed in all neurons recorded intracellularly. In some neurons, hyperpolarization was caused by inhibitory postsynaptic potentials, as demonstrated by reversal of membrane potential trajectory after intracellular chloride iontophoresis. Some individual motoneurons and interneurons exhibited both pulmonary and buccal ventilatory activity, indicating that both pattern generators project to a common motor control system. 1994 John Wiley & Sons, Inc. 相似文献