中枢听觉系统对声音时程的调谐和识别

声音的时程信息对动物的声通讯和人的言语识别非常重要。声信号中的大部分信息都编码在随时间变化的振幅和频谱中。听中枢神经元对声音时程的调谐先后在蛙、蝙蝠、小鼠等动物的下丘及以上结构内发现,其在声信号识别和声信息承载方面发挥重要作用;以人为对象的心理物理学研究也观察到发声的时程对语音识别和语义分析非常重要。时程调谐的神经机制目前尚不清楚,可能是兴奋性输入和抑制性输入按某种模式进行的整合。巧合检测模型和反巧合模型等可解释某些类型的时程选择性神经元上的调谐机制,而神经元自身的结构特性也可能与时程调谐的形成有关。时程调谐还受到声音的其他参量(如频谱构成、强度、重复率等)影响,时程选择性神经元可根据这些参量的动态变化凸显特殊生境下的有意义声信号。本文在相关研究工作基础之上,结合本实验室的研究结果,对中枢听神经元的时程编码特性和机制,以及某些声信号参数对神经元时程编码的影响和时程调谐的生物学意义作介绍和评述。     

外侧丘系腹核在声信号加工和听觉上行传导中的作用

外侧丘系腹核(ventral nucleus of the lateral lemniscus,VNLL)是中枢听觉通路中连接耳蜗核等低位脑干和中脑下丘(inferior colliculus,IC)的重要核团,其神经元能够对声信号的不同参数进行检测与加工,进而形成多样的声反应特性。VNLL神经元对频率反应的调谐曲线有多种类型,但其锐化程度一般较低,对频率的分析亦不够精确;有关强度调谐的放电率函数分为两种类型:单调型与非单调型,它们对强度的加工和编码往往受到发放模式的影响;不同发放模式的VNLL神经元对时程的编码能力不同,其中起始型具有精确的时间特性,适合编码声刺激的起始时间信息,对蝙蝠的回声定位非常重要。VNLL接受来自低位核团的输入,并发出上行的抑制性投射至IC,在IC神经元的声信息检测过程中发挥重要作用。近来研究认为VNLL快速的抑制性投射延迟IC神经元的首次发放潜伏期,VNLL延迟的抑制性投射介导IC神经元的发放模式,但VNLL抑制性输入如何在IC进行整合,并增强IC神经元检测声信号能力的机制并不清楚,且缺乏VNLL对IC进行实时调控作用的直接证据。这些问题的研究有助于进一步认识上行输入在声信号加工过程中的作用,同时也是本实验室今后的研究重点。本文结合本实验室相关研究,围绕VNLL对听觉信号的加工和上行传导进行综述。     

荷包牡丹碱和马钱子碱对小鼠皮层及下丘听神经元声反应潜伏期的影响

频率和强度是声音的两个重要参数,通常以听觉神经元动作电位发放频次编码这两个参数 . 研究表明,声反应潜伏期也可编码声音频率和强度,但尚不清楚潜伏期编码这两个参数究竟发生于哪一级听觉核团 . 如果声音参数由同级中枢编码,则这样的编码方式可能发生改变 . 反之,如果编码方式未发生变化,则意味着声音信息是由低位神经元编码的 . GABA 和甘氨酸 (Gly) 是听中枢普遍分布的抑制性递质 . 通过施加它们的拮抗剂荷包牡丹碱和马钱子碱,观测小鼠皮层和下丘听觉神经元声反应潜伏期的变化 . 结果表明,由反应潜伏期表征声音频率和强度的关系不因 GABA 和 Gly 作用的改变而发生变化,提示频率和强度与反应潜伏期之间的编码关系可能是由低位听神经元编码并向上传递的,而不是在同级中枢 ( 皮层或下丘 ) 完成的 .     

CF-FM蝙蝠听中枢神经元处理行为相关声信号的神经机制

蝙蝠具有高度发达的回声定位系统,能够准确地处理和整合不断变化环境中的声学参数,以保持最佳的生理和行为状态。这种行为的神经生理机制已经得到了广泛的研究。本文主要探究了CF-FM蝙蝠听觉中枢处理种属特异性声信号、共变参数、多普勒频移补偿信号及多谐波声信号的神经机制,可有助于了解回声定位蝙蝠处理行为相关声信号的神经策略。同时本文也提出将来可以CF-FM蝙蝠作为模式动物进行更深入的胞内研究。     

听觉信息的处理及分辨率的锐化

耳对声音的响应极快,但听觉的高分辨率依靠高级整合中枢对传入信息的处理。在一定范围内,对不同声参数的听觉辨别阈与声信号时程的平方根成反比,提示整合中枢按重复采样统计分析的工作方式提高辨别精度。利用复杂声中互相强化的多种依据检测声参数的变化,也是听觉分辨率锐化的基础。     

短声特性对豚鼠圆窗记录的N_1N_2反应的影响

研究了不同刺激声强情况下短声特性(极性、波形及相应频谱)改变对豚鼠圆窗记录的N_1N_2反应的影响。发现:①在低声强时,若维持刺激声强不变而使短声波形改变对N_1无影响,但是对N_2有轻微的影响。而高声强时,若维持刺激声强不变而使短声波形改变将引起N_N_2反应较为显著的变化。②不仅是短声的疏相,而且其密相对N_1N_2的形成有贡献。③N_1N_2反应不仅与短声刺激强度有关,而且还与短声的其它参数(如波宽等)有关。并就各项结果进行了讨论。     

综述与专论: 蝙蝠，听觉和回声定位研究的模型动物

科学家以蝙蝠为模式动物,从听觉、回声定位和生态适应与演化等方面开展了研究,取得了令人瞩目的成果。为适应回声定位,蝙蝠听觉系统的结构和功能产生了明显的特化。从外周到中枢形成了对声频率极为有序的表征,甚至在恒频-调频（constant frequency-frequency modulation,CF-FM）蝙蝠耳蜗形成了所谓的听觉凹,以及听皮质功能组构也模块化,成为了具有代表性的特化象征。神经元反应的潜伏期对蝙蝠不仅是基本特性,也是回声定位行为调控的一部分;研究发现,有较长潜伏期的神经元具有较尖锐的回声-延迟调谐特性,而较短潜伏期的神经元则有较宽的回声-延迟调谐特性。蝙蝠听神经元对频率调谐的精准度亦远胜于人类和其他非回声定位动物;而且,源于耳蜗听觉凹的传入在各级听中枢均显示出对回声定位信号第二谐波CF成分的过度表征,以满足对靶物回声多普勒频移探测的需要。时程是回声定位蝙蝠发声信号主动改变的参数之一,而时程调谐神经元则提供了一种编码声音时相特征的重要神经机制,匹配了对回声定位信号时相信息加工的需要。在多种回声定位蝙蝠的听中枢还发现,有回声-延迟调谐神经元,它们不仅能对靶物距离进行调谐,而且...     

综述: 渐近优先性及其机制

对渐近信号的优先加工被称为渐近优先性,该效应普遍存在于人类和动物的视觉、听觉和跨感觉通道中.人类神经影像学研究发现负责加工渐近信号的脑区涉及一个大规模相互协作和沟通的分布式神经网络,包括颞上沟、颞顶叶连接处以及一些运动区.对多种动物的细胞水平研究也发现了对渐近信号选择性敏感的神经元和神经通路.威胁论、注意捕获理论和自动加工理论从不同角度解释了渐近优先性产生的原因.未来研究可进一步考察刺激的社会、情绪等属性对渐近优先性的影响,探索多通道渐近渐远信息的整合和注意分配机制.     

渐近优先性及其机制

对渐近信号的优先加工被称为渐近优先性,该效应普遍存在于人类和动物的视觉、听觉和跨感觉通道中.人类神经影像学研究发现负责加工渐近信号的脑区涉及一个大规模相互协作和沟通的分布式神经网络,包括颞上沟、颞顶叶连接处以及一些运动区.对多种动物的细胞水平研究也发现了对渐近信号选择性敏感的神经元和神经通路.威胁论、注意捕获理论和自动加工理论从不同角度解释了渐近优先性产生的原因.未来研究可进一步考察刺激的社会、情绪等属性对渐近优先性的影响,探索多通道渐近渐远信息的整合和注意分配机制.     

普氏蹄蝠下丘单反应和双反应神经元加工多普勒频移补偿信号的特点及生理机制

恒频-调频(constant frequency-frequency modulation,CF-FM)蝙蝠独特的多普勒频移补偿(Doppler-shift compensation,DSC)行为可保证其对回声信息的精确提取.那么听中枢加工DSC信号的适应性机制是什么?本实验模拟CF-FM蝙蝠DSC后的回声定位信号,研究下丘(inferior colliculus,IC)神经元加工DSC信号的特点及生理机制.实验共获得117个IC神经元,在CF-FM声刺激下,神经元表现为single-on(SO,n=83)和double-on(DO,n=34)两种反应模式.无论是在蝙蝠的正向还是负向补偿过程中,SO和DO神经元对回声反应恢复到50%时的双声刺激间隔(inter-pulse interval,IPI)值,均会随补偿条件的改变而发生变化.当双声刺激由无补偿转变为最佳补偿条件时,两类神经元的50%IPI显著缩短(P0.001),但SO神经元50%IPI缩短率超过70%的神经元数目较DO神经元多,且偏好正向补偿的IC神经元中,SO神经元的平均DSC范围也要显著宽于DO神经元(P0.05).该研究结果提示,IC中SO神经元可能较DO神经元更能充分利用蝙蝠DSC行为,来提高对回声反应的恢复能力,以最大程度地获取猎物信息并准确判断与猎物的相对速度.     

Precognitive and cognitive elements in sound localization

Sound localization behavior is of great importance for an animal's survival. To localize a sound, animals have to detect a sound source and assign a location to it. In this review we discuss recent results on the underlying mechanisms and on modulatory influences in the barn owl, an auditory specialist with very well developed capabilities to localize sound. Information processing in the barn owl auditory pathway underlying the computations of detection and localization is well understood. This analysis of the sensory information primarily determines the following orienting behavior towards the sound source. However, orienting behavior may be modulated by cognitive (top-down) influences such as attention. We show how advanced stimulation techniques can be used to determine the importance of different cues for sound localization in quasi-realistic stimulation situations, how attentional influences can improve the response to behaviorally relevant stimuli, and how attention can modulate related neural responses. Taken together, these data indicate how sound localization might function in the usually complex natural environment.     

后掩蔽效应对大棕蝠下丘神经元声反应的影响

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。     

A corticothalamic circuit model for sound identification in complex scenes

The identification of the sound sources present in the environment is essential for the survival of many animals. However, these sounds are not presented in isolation, as natural scenes consist of a superposition of sounds originating from multiple sources. The identification of a source under these circumstances is a complex computational problem that is readily solved by most animals. We present a model of the thalamocortical circuit that performs level-invariant recognition of auditory objects in complex auditory scenes. The circuit identifies the objects present from a large dictionary of possible elements and operates reliably for real sound signals with multiple concurrently active sources. The key model assumption is that the activities of some cortical neurons encode the difference between the observed signal and an internal estimate. Reanalysis of awake auditory cortex recordings revealed neurons with patterns of activity corresponding to such an error signal.     

Effects of binaural decorrelation on neural and behavioral processing of interaural level differences in the barn owl (Tyto alba)

The effect of binaural decorrelation on the processing of interaural level difference cues in the barn owl (Tyto alba) was examined behaviorally and electrophysiologically. The electrophysiology experiment measured the effect of variations in binaural correlation on the first stage of interaural level difference encoding in the central nervous system. The responses of single neurons in the posterior part of the ventral nucleus of the lateral lemniscus were recorded to stimulation with binaurally correlated and binaurally uncorrelated noise. No significant differences in interaural level difference sensitivity were found between conditions. Neurons in the posterior part of the ventral nucleus of the lateral lemniscus encode the interaural level difference of binaurally correlated and binaurally uncorrelated noise with equal accuracy and precision. This nucleus therefore supplies higher auditory centers with an undegraded interaural level difference signal for sound stimuli that lack a coherent interaural time difference. The behavioral experiment measured auditory saccades in response to interaural level differences presented in binaurally correlated and binaurally uncorrelated noise. The precision and accuracy of sound localization based on interaural level difference was reduced but not eliminated for binaurally uncorrelated signals. The observation that barn owls continue to vary auditory saccades with the interaural level difference of binaurally uncorrelated stimuli suggests that neurons that drive head saccades can be activated by incomplete auditory spatial information.     

Postnatal development of auditory central evoked responses and thalamic cellular properties

During development, the sense of hearing changes rapidly with age, especially around hearing onset. During this period, auditory structures are highly sensitive to alterations of the acoustic environment, such as hearing loss or background noise. This sensitivity includes auditory temporal processing, which is important for processing complex sounds, and for acquiring reading and language skills. Developmental changes can be observed at multiple levels of brain organization—from behavioral responses to cellular responses, and at every auditory nucleus. Neuronal properties and sound processing change dramatically in auditory cortex neurons after hearing onset. However, development of its primary source, the auditory thalamus, or medial geniculate body (MGB), has not been well studied over this critical time window. Furthermore, to understand how temporal processing develops, it is important to determine the relative maturation of temporal processing not only in the MGB, but also in its inputs. Cellular properties of rat MGB neurons were studied using in vitro whole‐cell patch‐clamp recordings, at ages postnatal day (P) 7–9; P15–17, and P22–32. Auditory evoked potentials were measured in P14–17 and P22–32 rats. MGB action potentials became about five times faster, and the ability to generate spike trains increased with age, particularly at frequencies of 50 Hz and higher. Evoked potential responses, including auditory brainstem responses (ABR), middle latency responses (MLR), and amplitude modulation following responses, showed increased amplitudes with age, and ABRs and MLRs additionally showed decreased latencies with age. Overall, temporal processing at subthalamic nuclei is concurrently maturing with MGB cellular properties. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 74: 541–555, 2014     

A Neural Mechanism for Time-Window Separation Resolves Ambiguity of Adaptive Coding

The senses of animals are confronted with changing environments and different contexts. Neural adaptation is one important tool to adjust sensitivity to varying intensity ranges. For instance, in a quiet night outdoors, our hearing is more sensitive than when we are confronted with the plurality of sounds in a large city during the day. However, adaptation also removes available information on absolute sound levels and may thus cause ambiguity. Experimental data on the trade-off between benefits and loss through adaptation is scarce and very few mechanisms have been proposed to resolve it. We present an example where adaptation is beneficial for one task—namely, the reliable encoding of the pattern of an acoustic signal—but detrimental for another—the localization of the same acoustic stimulus. With a combination of neurophysiological data, modeling, and behavioral tests, we show that adaptation in the periphery of the auditory pathway of grasshoppers enables intensity-invariant coding of amplitude modulations, but at the same time, degrades information available for sound localization. We demonstrate how focusing the response of localization neurons to the onset of relevant signals separates processing of localization and pattern information temporally. In this way, the ambiguity of adaptive coding can be circumvented and both absolute and relative levels can be processed using the same set of peripheral neurons.     

Neural representations of the axis of acoustic particle motion in nucleus centralis of the torus semicircularis of the goldfish, <Emphasis Type="Italic">Carassius auratus</Emphasis>

Experiments examined differential coding of acoustic particle motion axis in the auditory midbrain of goldfish. Animals were exposed to vibratory stimuli varying in axis orientation as action potentials were recorded from single units in the central neuropil of nucleus centralis in the torus semicircularis. Response magnitudes as a function of stimulation axis were visualized in three dimensional plots called directional response profiles. These are generally comparable to directional responses observed among primary saccular afferents in having substantially vertical orientations. Distortions in shape from the peripheral patterns indicate neural information processing. A three-dimensional model was used to evaluate the hypothesis that responses in the auditory midbrain reflect the convergence of excitatory and inhibitory primary afferent-like responses. Model afferent inputs were generated and combined arithmetically. This analysis gives insight into the mechanisms of information processing that appear to occur in brainstem nuclei. The lack of diversity in best axis directions suggests that this mechanism alone cannot account for directional hearing abilities in this species. The roles that this directional representation and processing may play in directional hearing and sound source localization are not yet clear. Implications of these data on current models of fish directional hearing are discussed.     

High-order auditory filters.

The past year has seen some important advances in our understanding of central auditory function. Several central auditory neurons that differ from those in the periphery in their selectivity for various spectral and temporal parameters of complex sound have been described. Although central specializations for the processing of complex sound have been known for some time, recent findings suggest that these high-order filter properties are more widespread than previously thought. Significant progress has been made in our understanding of the neural mechanisms by which some high-order filter properties, such as delay-tuning, amplitude-tuning, and complex frequency tuning are performed by the central auditory system. New evidence has clarified the role of high-order auditory filters in auditory learning and perception, and the regions in which they are found.     

GABA-mediated modulation of the discharge pattern and rate-level function of two simultaneously recorded neurons in the inferior colliculus of the big brown bat, Eptesicus fuscus

Neurons in the central nucleus of the inferior colliculus (IC) receive excitatory and inhibitory inputs from both lower and higher auditory nuclei. Interaction of these two opposing inputs shapes response properties of IC neurons. In this study, we examine the interaction of excitation and inhibition on the responses of two simultaneously recorded IC neurons using a probe and a masker under forward masking paradigm. We specifically study whether a sound that serves as a probe to elicit responses of one neuron might serve as a masker to suppress or facilitate the responses of the other neuron. For each pair of IC neurons, we deliver the probe at the best frequency (BF) of one neuron and the masker at the BF of the other neuron and vice versa. Among 33 pairs of IC neurons recorded, this forward masking produces response suppression in 29 pairs of IC neurons and response facilitation in 4 pairs of IC neurons. The degree of suppression decreases with recording depth, sound level and BF difference between each pair of IC neurons. During bicuculline application, the degree of response suppression decreases in the bicuculline-applied neuron but increases in the paired neuron. Our data indicate that the forward masking of responses of IC neurons observed in this study is mostly mediated through GABAergic inhibition which also shapes the discharge pattern of these neurons. These data suggest that interaction among individual IC neurons improves auditory sensitivity during auditory signal processing.     

Philosophy and stimulus design for neuroethology of complex-sound processing.

In research on the neural mechanisms for the processing of biologically important sounds such as species-specific sounds and sounds produced by prey and predators, it is necessary to study responses of central auditory neurons to biologically important sounds, information-bearing elements (IBEs) in them, and tone bursts. The tone bursts or constant-frequency (CF) components can be an IBE in many species of animals. Information-bearing parameters characterizing these sounds must be systematically varied, and tuning of neurons to individual parameters must be studied. The measurement of a tuning curve must be performed not only for excitatory responses, but also for inhibitory and facilitative responses, if any. The selectivity of a neuron to a particular type of sound must be tested for whether it is level-tolerant. Responses to complex sounds can probably be explained on the basis of those to IBEs and tone bursts, so that the use of the tone bursts, even though they are not IBEs, is as essential as that of the biologically important sounds.