Balanced inhibition underlies tuning and sharpens spike timing in auditory cortex

Neurons in the primary auditory cortex are tuned to the intensity and specific frequencies of sounds, but the synaptic mechanisms underlying this tuning remain uncertain. Inhibition seems to have a functional role in the formation of cortical receptive fields, because stimuli often suppress similar or neighbouring responses, and pharmacological blockade of inhibition broadens tuning curves. Here we use whole-cell recordings in vivo to disentangle the roles of excitatory and inhibitory activity in the tone-evoked responses of single neurons in the auditory cortex. The excitatory and inhibitory receptive fields cover almost exactly the same areas, in contrast to the predictions of classical lateral inhibition models. Thus, although inhibition is typically as strong as excitation, it is not necessary to establish tuning, even in the receptive field surround. However, inhibition and excitation occurred in a precise and stereotyped temporal sequence: an initial barrage of excitatory input was rapidly quenched by inhibition, truncating the spiking response within a few (1-4) milliseconds. Balanced inhibition might thus serve to increase the temporal precision and thereby reduce the randomness of cortical operation, rather than to increase noise as has been proposed previously.     

脑对双耳听觉信息整合的神经机制

综述近60 a来有关脑对双耳听觉信息整合的神经机制的研究进展.首先介绍了脑处理双耳信息的神经解剖学基础，双耳神经元的分类及其生理特性，以及双耳神经元在听觉系统的拓扑学分布研究；然后对脑处理双耳听觉信息研究的热点领域进行了重点探讨，综述了上橄榄复合体、下丘和听皮层双耳神经元对双耳时间差和双耳强度差的编码方式，以及脑通过对这些参数的编码来分析声源方位的神经生理学研究进展；最后对该领域未来研究方向作展望.     

家鸽前脑声反应神经元的分布及其特性的研究

实验在61只家鸽上完成。动物用三碘季胺酚麻痹,记录了前脑36个神经元的电活动。实验结果表明,对短声刺激具有反应的前脑神经元分散地分布在旧纹状体、上纹状体以及新纹状体内,但是大多数听神经元集聚在相当于Karten和Hodos氏鸽脑立体定位图谱P_(1～3),L或R_(1～3)以及H_(2～6)的坐标范围之内。这些对声刺激有反应的听神经元的潜伏期为5～42msec。在正常情况下,神经元的潜伏期很少变化。前脑听神经元既可以接受对侧耳的信息,也可以接受同侧耳的信息。在旧纹状体内来自双耳信息的聚合可能引起相互抑制的结果。     

Induction of visual orientation modules in auditory cortex

Modules of neurons sharing a common property are a basic organizational feature of mammalian sensory cortex. Primary visual cortex (V1) is characterized by orientation modules--groups of cells that share a preferred stimulus orientation--which are organized into a highly ordered orientation map. Here we show that in ferrets in which retinal projections are routed into the auditory pathway, visually responsive neurons in 'rewired' primary auditory cortex are also organized into orientation modules. The orientation tuning of neurons within these modules is comparable to the tuning of cells in V1 but the orientation map is less orderly. Horizontal connections in rewired cortex are more patchy and periodic than connections in normal auditory cortex, but less so than connections in V1. These data show that afferent activity has a profound influence on diverse components of cortical circuitry, including thalamocortical and local intracortical connections, which are involved in the generation of orientation tuning, and long-range horizontal connections, which are important in creating an orientation map.     

青蛙下丘双耳强度差反应的模型研究

建立了一个基于青蛙下丘或半规隆凸（TS）神经元静态反应的数学计算模型，模型中既有来自同侧上橄榄核团（SON）的兴奋性投射，又有来自对侧上橄榄核团的抑制性投射，目的是理解被研究神经元的静态反应行为是怎样由较低层次的神经核团的特性及这些核团之间的连接方式所产生的，使用模型中的连接方式，并且神经元采用简单的输入输出关系，能够解释青蛙下丘神经元的这些行为，下丘神经元双耳间强度差（ILD）函数的方向性变化的主要因素是双耳抑制的存在。     

电刺激大鼠mPFC对听皮层神经元听反应的影响

实验在40只成年SD大鼠上进行,使用常规电生理学方法,观察了电刺激大鼠内侧额叶前皮质(medial prefrontal cortex, mPFC)对听皮层神经元听反应的影响.在122个神经元上观察了电刺激mPFC对听反应的影响.对其中93个神经元作了详细分析发现,有73个神经元的听反应受到易化（39个,41.9%）或抑制（34个,36.6%）.刺激mPFC对听反应的影响存在最佳刺激间隔,大多数神经元（51个,69%）在10~15 ms之间.结果提示,大鼠mPFC可对听皮层神经元的听反应调制,这种调制可能是通过多级神经元环路实现的.     

Topography of acoustic response characteristics in the auditory cortex of the Kunming mouse

Topography of acoustic response characteristics in the auditory cortex (AC) of the Kunming (KM) mouse has been examined by using microelectrode recording techniques. Based on best-frequency (BF) maps, both the primary auditory field (AI) and the anterior auditory field (AAF) are tonotopically organized with a counter running frequency gradient. Within an isofrequency stripe, the width of the frequency-threshold curves of single neurons increases, and minimum threshold (MT) decreases towards more ventral locations. BFs in AI and AAF range from 4 to 38 kHz. Auditory neurons with BFs above 40 kHz are located at the rostrodorsal part of the AC. The findings suggest that the KM mouse is a good model suitable for auditory research.     

Topography and synaptic shaping of direction selectivity in primary auditory cortex

The direction of frequency-modulated (FM) sweeps is an important temporal cue in animal and human communication. FM direction-selective neurons are found in the primary auditory cortex (A1), but their topography and the mechanisms underlying their selectivity remain largely unknown. Here we report that in the rat A1, direction selectivity is topographically ordered in parallel with characteristic frequency (CF): low CF neurons preferred upward sweeps, whereas high CF neurons preferred downward sweeps. The asymmetry of 'inhibitory sidebands', suppressive regions flanking the tonal receptive field (TRF) of the spike response, also co-varied with CF. In vivo whole-cell recordings showed that the direction selectivity already present in the synaptic inputs was enhanced by cortical synaptic inhibition, which suppressed the synaptic excitation of the non-preferred direction more than that of the preferred. The excitatory and inhibitory synaptic TRFs had identical spectral tuning, but with inhibition delayed relative to excitation. The spectral asymmetry of the synaptic TRFs co-varied with CF, as had direction selectivity and sideband asymmetry, and thus suggested a synaptic mechanism for the shaping of FM direction selectivity and its topographic ordering.     

家鸽前脑声反应神经元的分布及其特性的研究

实验在61只家鸽上完成。动物用三碘季胺酚麻痹,记录了前脑36个神经元的电活动。实验结果表明,对短声刺激具有反应的前脑神经元分散地分布在旧纹状体、上纹状体以及新纹状体内,但是大多数听神经元集聚在相当于Karten和Hodos氏鸽脑立体定位图谱P_(1-3),L或R_(1-3)以及H_(2-6)的坐标范围之内。这些对声刺激有反应的听神经元的潜伏期为5～42msec。在正常情况下,神经元的潜伏期很少变化。前脑听神经元既可以接受对侧耳的信息,也可以接受同侧耳的信息。在旧纹状体内来自双耳信息的聚合可能引起相互抑制的结果。     

Ultra-fine frequency tuning revealed in single neurons of human auditory cortex

Just-noticeable differences of physical parameters are often limited by the resolution of the peripheral sensory apparatus. Thus, two-point discrimination in vision is limited by the size of individual photoreceptors. Frequency selectivity is a basic property of neurons in the mammalian auditory pathway. However, just-noticeable differences of frequency are substantially smaller than the bandwidth of the peripheral sensors. Here we report that frequency tuning in single neurons recorded from human auditory cortex in response to random-chord stimuli is far narrower than that typically described in any other mammalian species (besides bats), and substantially exceeds that attributed to the human auditory periphery. Interestingly, simple spectral filter models failed to predict the neuronal responses to natural stimuli, including speech and music. Thus, natural sounds engage additional processing mechanisms beyond the exquisite frequency tuning probed by the random-chord stimuli.     

Precise inhibition is essential for microsecond interaural time difference coding

Microsecond differences in the arrival time of a sound at the two ears (interaural time differences, ITDs) are the main cue for localizing low-frequency sounds in space. Traditionally, ITDs are thought to be encoded by an array of coincidence-detector neurons, receiving excitatory inputs from the two ears via axons of variable length ('delay lines'), to create a topographic map of azimuthal auditory space. Compelling evidence for the existence of such a map in the mammalian lTD detector, the medial superior olive (MSO), however, is lacking. Equally puzzling is the role of a--temporally very precise glycine--mediated inhibitory input to MSO neurons. Using in vivo recordings from the MSO of the Mongolian gerbil, we found the responses of ITD-sensitive neurons to be inconsistent with the idea of a topographic map of auditory space. Moreover, local application of glycine and its antagonist strychnine by iontophoresis (through glass pipette electrodes, by means of an electric current) revealed that precisely timed glycine-controlled inhibition is a critical part of the mechanism by which the physiologically relevant range of ITDs is encoded in the MSO. A computer model, simulating the response of a coincidence-detector neuron with bilateral excitatory inputs and a temporally precise contralateral inhibitory input, supports this conclusion.     

Role of frequency band integration in sharpening frequency tunings of the inferior colliculus neurons in the big brown bat,<Emphasis Type="Italic">Eptesicus fuscus</Emphasis>

By means of a particular two-tone stimulationparadigm in combination of using a pair of electrodes forsimultaneously recording from two inferior colliculus (IC)neurons, the current in vivo study is undertaken to explorethe role of frequency band integration (FBI) in sharpening offrequency tuning in the big brown bat, Eptesicus fuscus.Three major results are found: (1) The paired neurons cor-related to FBI are located not only within the same frequencyfilter bandwidth (FFB), but also across different FFBs. Therelations of their frequency tuning curves (FTCs) are mainlyof two types: the flank-overlapped and overlaid patterns. (2)Although the sharpness of FTCs between paired neurons ismutual, the sharpening efficiency of neurons located withinthe same FFB is higher than that of neurons across FFBs,and the FTCs of neurons with the best frequencies (BF) of 20--30 kHz are most strongly sharpened. (3) The strength ofFBI is weak near the BF but gradually increased with fre-quencies away from the BF of sound stimuli. This suggeststhat the dynamical FBI of the IC neurons located within and across the FFBs might be involved in the formation of func-tional FFB structures.     

刺激大鼠杏仁外侧核对听皮层神经元调频声反应的影响

采用在体细胞外单细胞记录方法,研究电刺激杏仁外侧核对调频声所诱发的听皮层神经元反应的影响.实验在34只乌拉坦麻醉的SD大鼠上进行,在皮层41区记录了113个对调频声有反应的细胞电活动.观察发现,这些神经元对调频声刺激的反应可分为ON反应,OFF反应,ON-OFF反应,持续性反应和给声抑制反应几种类型.在观察对其中42个神经元的声反应时给予了杏仁外侧核电刺激,其中22%的神经元反应被易化,48%的神经元反应受到了抑制,另外30%神经元的声反应未受杏仁外侧核刺激的影响.这些影响进一步表明,杏仁复合体可在皮层水平参与听觉上传信息的处理,包括听觉信息的加工与整合.同时也表明杏仁核在上传听觉信息的筛选中可能具有重要的作用.     

大鼠杏仁体基底核对视皮层17区神经元电活动的抑制

实验在５５只Ｕｒｅｔｈａｎｅ麻醉的雄性Ｓ磊鼠上进行。采用电生理的胞外记录法,观察了电刺激杏杜体对视皮层１７区单个神经元的光反应及自发放电活动的影响。当刺激杏仁体基底核时,１２３个对闪光起反应的神经元中,有５７个单位的光反应受到了抑制（占４６．３％）。这种帽性影响的潜伏期多为５－５０ｍｓ（３３个单位）,抑制的有效时程为５－２０ｍｓ。本文对这种抑制性影响的可能途径和生物学意义进行了讨论。     

Potentiation of cortical inhibition by visual deprivation

The fine-tuning of circuits in sensory cortex requires sensory experience during an early critical period. Visual deprivation during the critical period has catastrophic effects on visual function, including loss of visual responsiveness to the deprived eye, reduced visual acuity, and loss of tuning to many stimulus characteristics. These changes occur faster than the remodelling of thalamocortical axons, but the intracortical plasticity mechanisms that underlie them are incompletely understood. Long-term depression of excitatory intracortical synapses has been proposed as a general candidate mechanism for the loss of cortical responsiveness after visual deprivation. Alternatively (or in addition), the decreased ability of the deprived eye to activate cortical neurons could be due to enhanced intracortical inhibition. Here we show that visual deprivation leaves excitatory connections in layer 4 (the primary input layer to cortex) unaffected, but markedly potentiates inhibitory feedback between fast-spiking basket cells (FS cells) and star pyramidal neurons (star pyramids). Further, a previously undescribed form of long-term potentiation of inhibition (LTPi) could be induced at synapses from FS cells to star pyramids, and was occluded by previous visual deprivation. These data suggest that potentiation of inhibition is a major cellular mechanism underlying the deprivation-induced degradation of visual function, and that this form of LTPi is important in fine-tuning cortical circuitry in response to visual experience.     

黄雀(Carduelis spinus)上橄榄核的传入性联系—HRP顺逆行追踪法研究

分别将HRP微电泳入黄雀的上橄榄核(SO)、角状核、层状核和巨细胞核,观察其顺、逆行标记物的分布.结果表明,SO接受同侧层状标和双侧角状核的传入,双侧SO之间有交互投射,SO的纤维投射至外侧丘系核腹侧部、外侧丘系腹核和中脑背外侧核.因此,它属于听觉传入通路中的第二级中继站.此外,SO向巨细胞核投射并形成巨细胞核→层状核→SO→巨细胞核的闭合环路.此环路可能参与听觉信息的反馈及声源定向等的初步整合机能.     

Activation of specific interneurons improves V1 feature selectivity and visual perception

Inhibitory interneurons are essential components of the neural circuits underlying various brain functions. In the neocortex, a large diversity of GABA (γ-aminobutyric acid) interneurons has been identified on the basis of their morphology, molecular markers, biophysical properties and innervation pattern. However, how the activity of each subtype of interneurons contributes to sensory processing remains unclear. Here we show that optogenetic activation of parvalbumin-positive (PV+) interneurons in the mouse primary visual cortex (V1) sharpens neuronal feature selectivity and improves perceptual discrimination. Using multichannel recording with silicon probes and channelrhodopsin-2 (ChR2)-mediated optical activation, we found that increased spiking of PV+ interneurons markedly sharpened orientation tuning and enhanced direction selectivity of nearby neurons. These effects were caused by the activation of inhibitory neurons rather than a decreased spiking of excitatory neurons, as archaerhodopsin-3 (Arch)-mediated optical silencing of calcium/calmodulin-dependent protein kinase IIα (CAMKIIα)-positive excitatory neurons caused no significant change in V1 stimulus selectivity. Moreover, the improved selectivity specifically required PV+ neuron activation, as activating somatostatin or vasointestinal peptide interneurons had no significant effect. Notably, PV+ neuron activation in awake mice caused a significant improvement in their orientation discrimination, mirroring the sharpened V1 orientation tuning. Together, these results provide the first demonstration that visual coding and perception can be improved by increased spiking of a specific subtype of cortical inhibitory interneurons.     

Topography of acoustic response characteristics in the midbrain inferior colliculus of Kunming mouse

Topography of acoustic response characteristics of the midbrain inferior colliculus(IC)of the Kunming mouse was studied by using extracellular recording techniques.The characteristic frequency(CF)range represented in the different divisions of the IC differed markedly:4-15 kHz in the dorsal cortex(DC),10-70 kHz in the central nucleus(CN),and 4-35kHz in the external cortex(EC).The CF in the CN increased from dorsal and lateral to ventral and medial,higher CFs represented at its ventromedial part and lower CFs at its dorsal part.The isofrequency contours of CFs were incurvate.Minimum thresholds(MT)of the auditory neurons in DC and the central part of CN were lower(about 10dB SPL),but considerably higher in the dorsal and ventral region of EC.Results suggest that each of the divisions in the mouse IC may have different auditory functions.     

Corticofugal modulation of frequency tuning of inferior collicular neurons in big brown bat,Eptesicus fuscus

In order to explore the possible mechanism of corticofugal modulation of excitatory frequency tuning curves (EFTCs) of midbrain neurons, we examined the change of sharpness, frequency-intensity response area, minimum threshold of both EFTCs and inhibitory frequency tuning curves (IFTCs) of inferior collicular neurons during corticofugal modulation using two-tone inhibition paradigm and micro-electrical stimulation technique. Our data showed that corticofugal inhibition increased sharpness, minimum threshold, and decreased the frequency-intensity response area of EFTCs, at the same time it decreased the sharpness, minimum threshold but increased the frequency-intensity response area of IFTCs. The opposite results were observed for EFTCs and IFTCs of corticofugally facilitated inferior collicular neurons. During corticofugal inhibition, the percent change of frequency-intensity response area of EFTCs had significant correlation with the percent change of that of IFTCs. These data suggest that cortical neurons are likely to improve frequency information processing of inferior collicular neurons by modulation of IFTCs.     

Sustained firing in auditory cortex evoked by preferred stimuli

It has been well documented that neurons in the auditory cortex of anaesthetized animals generally display transient responses to acoustic stimulation, and typically respond to a brief stimulus with one or fewer action potentials. The number of action potentials evoked by each stimulus usually does not increase with increasing stimulus duration. Such observations have long puzzled researchers across disciplines and raised serious questions regarding the role of the auditory cortex in encoding ongoing acoustic signals. Contrary to these long-held views, here we show that single neurons in both primary (area A1) and lateral belt areas of the auditory cortex of awake marmoset monkeys (Callithrix jacchus) are capable of firing in a sustained manner over a prolonged period of time, especially when they are driven by their preferred stimuli. In contrast, responses become more transient or phasic when auditory cortex neurons respond to non-preferred stimuli. These findings suggest that when the auditory cortex is stimulated by a sound, a particular population of neurons fire maximally throughout the duration of the sound. Responses of other, less optimally driven neurons fade away quickly after stimulus onset. This results in a selective representation of the sound across both neuronal population and time.