A neuronal mechanism for sensory gating during locomotion in a vertebrate

The response of the foot to touch during walking depends on whether it is in the air or on the ground. In most animals, reflex responses to external stimuli are similarly adapted to their timing in the locomotor cycle, but there is only fragmentary information about the neural mechanisms involved. In arthropods, reflex modulation can occur in the sensory receptors themselves and in neurons that discharge during locomotion. By recording with dye-filled microelectrodes from neurons in the spinal cord of frog embryos, we describe reflex modulation at the level of sensory interneurons. Sensory inputs from skin receptors excite a specific class of spinal sensory interneuron whose activity leads to reflex bending of the body away from the stimulus. During swimming, these inputs are gated by rhythmic postsynaptic inhibition, so that sensory drive reaches motor neurons only at phases in the locomotor cycle when the resulting contraction would likewise turn the embryo away from the stimulated side. Such gating of sensory pathways could be a general feature of all locomotor systems where responses to sensory stimuli need to be adapted to the phase of locomotion.     

Influence of the thalamus on spatial visual processing in frontal cortex

Each of our movements activates our own sensory receptors, and therefore keeping track of self-movement is a necessary part of analysing sensory input. One way in which the brain keeps track of self-movement is by monitoring an internal copy, or corollary discharge, of motor commands. This concept could explain why we perceive a stable visual world despite our frequent quick, or saccadic, eye movements: corollary discharge about each saccade would permit the visual system to ignore saccade-induced visual changes. The critical missing link has been the connection between corollary discharge and visual processing. Here we show that such a link is formed by a corollary discharge from the thalamus that targets the frontal cortex. In the thalamus, neurons in the mediodorsal nucleus relay a corollary discharge of saccades from the midbrain superior colliculus to the cortical frontal eye field. In the frontal eye field, neurons use corollary discharge to shift their visual receptive fields spatially before saccades. We tested the hypothesis that these two components-a pathway for corollary discharge and neurons with shifting receptive fields-form a circuit in which the corollary discharge drives the shift. First we showed that the known spatial and temporal properties of the corollary discharge predict the dynamic changes in spatial visual processing of cortical neurons when saccades are made. Then we moved from this correlation to causation by isolating single cortical neurons and showing that their spatial visual processing is impaired when corollary discharge from the thalamus is interrupted. Thus the visual processing of frontal neurons is spatiotemporally matched with, and functionally dependent on, corollary discharge input from the thalamus. These experiments establish the first link between corollary discharge and visual processing, delineate a brain circuit that is well suited for mediating visual stability, and provide a framework for studying corollary discharge in other sensory systems.     

Neural substrates of vocalization feedback monitoring in primate auditory cortex

Vocal communication involves both speaking and hearing, often taking place concurrently. Vocal production, including human speech and animal vocalization, poses a number of unique challenges for the auditory system. It is important for the auditory system to monitor external sounds continuously from the acoustic environment during speaking despite the potential for sensory masking by self-generated sounds. It is also essential for the auditory system to monitor feedback of one's own voice. This self-monitoring may play a part in distinguishing between self-generated or externally generatedauditory inputs and in detecting errors in our vocal production. Previous work in humans and other animals has demonstrated that the auditory cortex is largely suppressed during speaking or vocalizing. Despite the importance of self-monitoring, the underlying neural mechanisms in the mammalian brain, in particular the role of vocalization-induced suppression, remain virtually unknown. Here we show that neurons in the auditory cortex of marmoset monkeys (Callithrix jacchus) are sensitive to auditory feedback during vocal production, and that changes in the feedback alter the coding properties of these neurons. Furthermore, we found that the previously described cortical suppression during vocalization actually increased the sensitivity of these neurons to vocal feedback. This heightened sensitivity to vocal feedback suggests that these neurons may have an important role in auditory self-monitoring.     

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.     

A possible neuronal basis for Doppler-shift compensation in echo-locating horseshoe bats

The auditory system of the horseshoe bat is finely tuned to the bat's individual vocalization frequency. To compensate for flight-induced Doppler shifts in the echo frequency, the horseshoe bat adjusts the frequency of its echo-location call to maintain the echo frequency within the narrow range to which its auditory system is best tuned. In this report I describe neurons in the midbrain tegmentum of the horseshoe bat, with properties that strongly indicate their involvement in this Doppler-shift compensation. The activity of these neurons was influenced by both sound emission and auditory stimuli. Neuronal discharges in response to vocalization, however, differed from those in response to purely auditory stimuli that mimicked the bat call. When an auditory stimulus was temporally locked to a preceding vocalization, the response was dependent on the time delay between the two. This delay-sensitivity completely disappeared when vocalizations were simulated acoustically. Only those vocalization and 'echo' parameters were encoded that occur in Doppler-shift compensation. In conclusion, I suggest a model for the regulation of the vocalization frequency through auditory feedback.     

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。     

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。     

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.     

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.     

Auditory cortical responses in the cat to sounds that produce spatial illusions.

Humans and cats can localize a sound source accurately if its spectrum is fairly broad and flat, as is typical of most natural sounds. However, if sounds are filtered to reduce the width of the spectrum, they result in illusions of sources that are very different from the actual locations, particularly in the up/down and front/back dimensions. Such illusions reveal that the auditory system relies on specific characteristics of sound spectra to obtain cues for localization. In the auditory cortex of cats, temporal firing patterns of neurons can signal the locations of broad-band sounds. Here we show that such spike patterns systematically mislocalize sounds that have been passed through a narrow-band filter. Both correct and incorrect locations signalled by neurons can be predicted quantitatively by a model of spectral processing that also predicts correct and incorrect localization judgements by human listeners. Similar cortical mechanisms, if present in humans, could underlie human auditory spatial perception.     

Polyamine-dependent facilitation of postsynaptic AMPA receptors counteracts paired-pulse depression.

At many glutamatergic synapses in the brain, calcium-permeable alpha - amino - 3 - hydro - 5 - methyl - 4 - isoxazolepropionate receptor (AMPAR) channels mediate fast excitatory transmission. These channels are blocked by endogenous intracellular polyamines, which are found in virtually every type of cell. In excised patches, use-dependent relief of polyamine block enhances glutamate-evoked currents through recombinant and native calcium-permeable, polyamine-sensitive AMPAR channels. The contribution of polyamine unblock to synaptic currents during high-frequency stimulation may be to facilitate currents and maintain current amplitudes in the face of a slow recovery from desensitization or presynaptic depression. Here we show, on pairs and triples of synaptically connected neurons in slices, that this mechanism contributes to short-term plasticity in local circuits formed by presynaptic pyramidal neurons and postsynaptic multipolar interneurons in layer 2/3 of rat neocortex. Activity-dependent relief from polyamine block of postsynaptic calcium-permeable AMPARs in the interneurons either reduces the rate of paired-pulse depression in a frequency-dependent manner or, at a given stimulation frequency, induces facilitation of a synaptic response that would otherwise depress. This mechanism for the enhancement of synaptic gain appears to be entirely postsynaptic.     

Cortical remodelling induced by activity of ventral tegmental dopamine neurons.

Representations of sensory stimuli in the cerebral cortex can undergo progressive remodelling according to the behavioural importance of the stimuli. The cortex receives widespread projections from dopamine neurons in the ventral tegmental area (VTA), which are activated by new stimuli or unpredicted rewards, and are believed to provide a reinforcement signal for such learning-related cortical reorganization. In the primary auditory cortex (AI) dopamine release has been observed during auditory learning that remodels the sound-frequency representations. Furthermore, dopamine modulates long-term potentiation, a putative cellular mechanism underlying plasticity. Here we show that stimulating the VTA together with an auditory stimulus of a particular tone increases the cortical area and selectivity of the neural responses to that sound stimulus in AI. Conversely, the AI representations of nearby sound frequencies are selectively decreased. Strong, sharply tuned responses to the paired tones also emerge in a second cortical area, whereas the same stimuli evoke only poor or non-selective responses in this second cortical field in naive animals. In addition, we found that strong long-range coherence of neuronal discharge emerges between AI and this secondary auditory cortical area.     

调频声频率变化率对大鼠听皮层神经元声反应的影响

采用在体细胞外单细胞记录方法,研究调频声频率变化率及时程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,调频声刺激的时程和频率变化率发生改变,可对诱发的听皮层神经元反应的反应型式和放电频数产生影响.这种影响表明,听皮层在复杂声上传信息的处理过程中可能存在复杂的编码机制.     

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.     

动态阈值谱法语音增强

根据人耳能从噪声中提取有用信息的听觉特征，并结合语音信号的基本特征，提出并研究了一个适合于语音增强的听党内模型；实验结果表明，这个方法不仅在提高语音信噪比方面，而且在减小语音失真度方面均有较好的改善。     

Linear processing of spatial cues in primary auditory cortex.

To determine the direction of a sound source in space, animals must process a variety of auditory spatial cues, including interaural level and time differences, as well as changes in the sound spectrum caused by the direction-dependent filtering of sound by the outer ear. Behavioural deficits observed when primary auditory cortex (A1) is damaged have led to the widespread view that A1 may have an essential role in this complex computational task. Here we show, however, that the spatial selectivity exhibited by the large majority of A1 neurons is well predicted by a simple linear model, which assumes that neurons additively integrate sound levels in each frequency band and ear. The success of this linear model is surprising, given that computing sound source direction is a necessarily nonlinear operation. However, because linear operations preserve information, our results are consistent with the hypothesis that A1 may also form a gateway to higher, more specialized cortical areas.     

The origin of spontaneous activity in the developing auditory system

Spontaneous activity in the developing auditory system is required for neuronal survival as well as the refinement and maintenance of tonotopic maps in the brain. However, the mechanisms responsible for initiating auditory nerve firing in the absence of sound have not been determined. Here we show that supporting cells in the developing rat cochlea spontaneously release ATP, which causes nearby inner hair cells to depolarize and release glutamate, triggering discrete bursts of action potentials in primary auditory neurons. This endogenous, ATP-mediated signalling synchronizes the output of neighbouring inner hair cells, which may help refine tonotopic maps in the brain. Spontaneous ATP-dependent signalling rapidly subsides after the onset of hearing, thereby preventing this experience-independent activity from interfering with accurate encoding of sound. These data indicate that supporting cells in the organ of Corti initiate electrical activity in auditory nerves before hearing, pointing to an essential role for peripheral, non-sensory cells in the development of central auditory pathways.     

Genetic ablation reveals that the roof plate is essential for dorsal interneuron specification

During neural development in vertebrates, a spatially ordered array of neurons is generated in response to inductive signals derived from localized organizing centres. One organizing centre that has been proposed to have a role in the control of neural patterning is the roof plate. To define the contribution of signals derived from the roof plate to the specification of neuronal cell types in the dorsal neural tube, we devised a genetic strategy to ablate the roof plate selectively in mouse embryos. Embryos without a roof plate lack all the interneuron subtypes that are normally generated in the dorsal third of the neural tube. Using a genetically based lineage analysis and in vitro assays, we show that the loss of these neurons results from the elimination of non-autonomous signals provided by the roof plate. These results reveal that the roof plate is essential for specifying multiple classes of neurons in the mammalian central nervous system.     

Mechanisms and circuitry underlying directional selectivity in the retina

In the retina, directionally selective ganglion cells respond with robust spiking to movement in their preferred direction, but show minimal response to movement in the opposite, or null, direction. The mechanisms and circuitry underlying this computation have remained controversial. Here we show, by isolating the excitatory and inhibitory inputs to directionally selective cells and measuring direct connections between these cells and presynaptic neurons, that a presynaptic interneuron, the starburst amacrine cell, delivers direct inhibition to directionally selective cells. The processes of starburst cells are connected asymmetrically to directionally selective cells: those pointing in the null direction deliver inhibition; those pointing in the preferred direction do not. Starburst cells project inhibition laterally ahead of a stimulus moving in the null direction. In addition, starburst inhibition is itself directionally selective: it is stronger for movement in the null direction. Excitation in response to null direction movement is reduced by an inhibitory signal acting at a site that is presynaptic to the directionally selective cell. The interplay of these components generates reduced excitation and enhanced inhibition in the null direction, thereby ensuring robust directional selectivity.     

Acceleration of beta-receptor desensitization in combined administration of antidepressants and phenoxybenzamine

The delayed therapeutic effects of antidepressants (usually between 10 and 14 days) and of the tricyclic antidepressants in particular, are believed (on the basis of animal experiments) to lie in a progressive decrease of the sensitivity of cortical beta-adrenergic receptors. This is thought to be due to an increase in the synaptic concentration of noradrenaline, in turn accomplished by a decrease in the sensitivity of the presynaptic alpha 2 receptors which normally regulate noradrenaline secretion by a negative feedback mechanism. This model suggests that the desensitization of postsynaptic beta-receptors by antidepressants should be accelerated by the inhibition of the presynaptic alpha 2- adrenergic system, and we have indeed observed such an effect in preliminary studies with desipramine and phenoxybenzamine (PBZ) combined. We now show that the administration of either tricyclic or monoamine oxidase inhibitor antidepressants in combination with PBZ, an irreversible alpha-adrenergic blocker, accelerates and intensifies the desensitization of beta-adrenergic receptors. Our observations may have therapeutic implications.