Nonlinear cross-frequency interactions in primary auditory cortex spectrotemporal receptive fields: a Wiener–Volterra analysis

The effects of nonlinear interactions between different sound frequencies on the responses of neurons in primary auditory cortex (AI) have only been investigated using two-tone paradigms. Here we stimulated with relatively dense, Poisson-distributed trains of tone pips (with frequency ranges spanning five octaves, 16 frequencies /octave, and mean rates of 20 or 120 pips /s), and examined within-frequency (or auto-frequency) and cross-frequency interactions in three types of AI unit responses by computing second-order “Poisson-Wiener” auto- and cross-kernels. Units were classified on the basis of their spectrotemporal receptive fields (STRFs) as “double-peaked”, “single-peaked” or “peak-valley”. Second-order interactions were investigated between the two bands of excitatory frequencies on double-peaked STRFs, between an excitatory band and various non-excitatory bands on single-peaked STRFs, and between an excitatory band and an inhibitory sideband on peak-valley STRFs. We found that auto-frequency interactions (i.e., those within a single excitatory band) were always characterized by a strong depression of (first-order) excitation that decayed with the interstimulus lag up to ～200 ms. That depression was weaker in cross-frequency compared to auto-frequency interactions for ～25% of dual-peaked STRFs, evidence of “combination sensitivity” for the two bands. Non-excitatory and inhibitory frequencies (on single-peaked and peak-valley STRFs, respectively) typically weakly depressed the excitatory response at short interstimulus lags (<50 ms), but weakly facilitated it at longer lags (～50–200 ms). Both the depression and especially the facilitation were stronger for interactions with inhibitory frequencies rather than just non-excitatory ones. Finally, facilitation in single-peaked and peak-valley units decreased with increasing stimulus density. Our results indicate that the strong combination sensitivity and cross-frequency facilitation suggested by previous two-tone-paradigm studies are much less pronounced when using more temporally-dense stimuli.     

Central mechanisms of tactile shape perception

Studies show that while the cortical mechanisms of two-dimensional (2D) form and motion processing are similar in touch and vision, the mechanisms of three-dimensional (3D) shape processing are different. 2D form and motion are processed in areas 3b and 1 of SI cortex by neurons with receptive fields (RFs) composed of excitatory and inhibitory subregions. 3D shape is processed in area 2 and SII and relies on the integration of cutaneous and proprioceptive inputs. The RFs of SII neurons vary in size and shape with heterogeneous structures consisting of orientation-tuned fingerpads mixed with untuned excitatory or inhibitory fingerpads. Furthermore, the sensitivity of the neurons to cutaneous inputs changes with hand conformation. We hypothesize that these RFs are the kernels underlying tactile object recognition.     

Columnar Connectivity and Laminar Processing in Cat Primary Auditory Cortex

Background

Radial intra- and interlaminar connections form a basic microcircuit in primary auditory cortex (AI) that extracts acoustic information and distributes it to cortical and subcortical networks. Though the structure of this microcircuit is known, we do not know how the functional connectivity between layers relates to laminar processing.

Methodology/Principal Findings

We studied the relationships between functional connectivity and receptive field properties in this columnar microcircuit by simultaneously recording from single neurons in cat AI in response to broadband dynamic moving ripple stimuli. We used spectrotemporal receptive fields (STRFs) to estimate the relationship between receptive field parameters and the functional connectivity between pairs of neurons. Interlaminar connectivity obtained through cross-covariance analysis reflected a consistent pattern of information flow from thalamic input layers to cortical output layers. Connection strength and STRF similarity were greatest for intralaminar neuron pairs and in supragranular layers and weaker for interlaminar projections. Interlaminar connection strength co-varied with several STRF parameters: feature selectivity, phase locking to the stimulus envelope, best temporal modulation frequency, and best spectral modulation frequency. Connectivity properties and receptive field relationships differed for vertical and horizontal connections.

Conclusions/Significance

Thus, the mode of local processing in supragranular layers differs from that in infragranular layers. Therefore, specific connectivity patterns in the auditory cortex shape the flow of information and constrain how spectrotemporal processing transformations progress in the canonical columnar auditory microcircuit.     

Network Models of Frequency Modulated Sweep Detection

Frequency modulated (FM) sweeps are common in species-specific vocalizations, including human speech. Auditory neurons selective for the direction and rate of frequency change in FM sweeps are present across species, but the synaptic mechanisms underlying such selectivity are only beginning to be understood. Even less is known about mechanisms of experience-dependent changes in FM sweep selectivity. We present three network models of synaptic mechanisms of FM sweep direction and rate selectivity that explains experimental data: (1) The ‘facilitation’ model contains frequency selective cells operating as coincidence detectors, summing up multiple excitatory inputs with different time delays. (2) The ‘duration tuned’ model depends on interactions between delayed excitation and early inhibition. The strength of delayed excitation determines the preferred duration. Inhibitory rebound can reinforce the delayed excitation. (3) The ‘inhibitory sideband’ model uses frequency selective inputs to a network of excitatory and inhibitory cells. The strength and asymmetry of these connections results in neurons responsive to sweeps in a single direction of sufficient sweep rate. Variations of these properties, can explain the diversity of rate-dependent direction selectivity seen across species. We show that the inhibitory sideband model can be trained using spike timing dependent plasticity (STDP) to develop direction selectivity from a non-selective network. These models provide a means to compare the proposed synaptic and spectrotemporal mechanisms of FM sweep processing and can be utilized to explore cellular mechanisms underlying experience- or training-dependent changes in spectrotemporal processing across animal models. Given the analogy between FM sweeps and visual motion, these models can serve a broader function in studying stimulus movement across sensory epithelia.     

Frequency resolution and spectral integration (critical band analysis) in single units of the cat primary auditory cortex

Frequency resolution and spectral filtering in the cat primary auditory cortex (AI) were mapped by extracellular recordings of tone responses in white noise of various bandwidths. Single-tone excitatory tuning curves, critical bandwidths, and critical ratios were determined as a function of neuronal characteristic frequency and tone level. Single-tone excitatory tuning curves are inadequate measures of frequency resolution and spectral filtering in the AI, because their shapes (in most neurons) deviated substantially from the shapes of “tuning curves for complex sound analysis”, the curves determined by the band limits of the critical bandwidths. Perceptual characteristics of spectral filtering (intensity independence and frequency dependence) were found in average critical bandwidths of neurons from the central and ventral AI. The highest frequency resolution (smallest critical bandwidths) reached by neurons in the central and ventral AI equaled the psychophysical frequency resolution. The dorsal AI is special, since most neurons there had response properties incompatible with psychophysical features of frequency resolution. Perceptual characteristics of critical ratios were not found in the average neuronal responses in any area of the AI. It seems that spectral integration in the way proposed to be the basis for the perception of tones in noise is not present at the level of the AI. Accepted: 21 July 1997     

Cooperative nonlinearities in auditory cortical neurons

Cortical receptive fields represent the signal preferences of sensory neurons. Receptive fields are thought to provide a representation of sensory experience from which the cerebral cortex may make interpretations. While it is essential to determine a neuron's receptive field, it remains unclear which features of the acoustic environment are specifically represented by neurons in the primary auditory cortex (AI). We characterized cat AI spectrotemporal receptive fields (STRFs) by finding both the spike-triggered average (STA) and stimulus dimensions that maximized the mutual information between response and stimulus. We derived a nonlinearity relating spiking to stimulus projection onto two maximally informative dimensions (MIDs). The STA was highly correlated with the first MID. Generally, the nonlinearity for the first MID was asymmetric and often monotonic in shape, while the second MID nonlinearity was symmetric and nonmonotonic. The joint nonlinearity for both MIDs revealed that most first and second MIDs were synergistic and thus should be considered conjointly. The difference between the nonlinearities suggests different possible roles for the MIDs in auditory processing.     

Spatio-temporal organization of receptive fields of the cat striate cortex

The responses of cortical cells to gratings and bars were compared. The excitatory and inhibitory on-and off-zones of a simple cell are composed of on- and off-subfields of CGL. Any zone is formed by an opponent pair of subfields one of which gives an excitatory effect, the other — inhibitory. Such organization assumes the linear properties of a simple field. The deviations from linearity are due to spatial dis-placements of the subfields, heterogeneity of subfields, or the absence of one subfield in the opponent pair. Subfields may be both phasic and tonic, even in the same RF. Analysis of the most common type of a complex cell with modulated responses against unmodulated background shows that a mask eliminating stimulation of any half of the RF causes (according to the theory of filtres) increasing the bandwidth due to the increase or the appearance of responses to side low and high frequencies. The modulated components of the responses from both halves of the RF are out of phase. Analysis of this fact and the responses to thin bars suggests that a complex field is formed by linear and nonlinear subsystems converging onto output neuron. Other types of complex fields are organized by different combinations of subsystems. Limited in area by masking the RF responds to much higher spatial frequencies than the whole RF. The optimal frequency in two-dimensional spatial frequency characteristics of the RF does not change with orientation. Simple RFs and a part of complex RF calculate the amplitude and the phase of the stimulus, the other part of complex RFs (with unmodulated response) calculate only amplitude. Given all this, the RFs are grating filters of spatial frequency.     

Coexistence of lateral and co-tuned inhibitory configurations in cortical networks

The responses of neurons in sensory cortex depend on the summation of excitatory and inhibitory synaptic inputs. How the excitatory and inhibitory inputs scale with stimulus depends on the network architecture, which ranges from the lateral inhibitory configuration where excitatory inputs are more narrowly tuned than inhibitory inputs, to the co-tuned configuration where both are tuned equally. The underlying circuitry that gives rise to lateral inhibition and co-tuning is yet unclear. Using large-scale network simulations with experimentally determined connectivity patterns and simulations with rate models, we show that the spatial extent of the input determined the configuration: there was a smooth transition from lateral inhibition with narrow input to co-tuning with broad input. The transition from lateral inhibition to co-tuning was accompanied by shifts in overall gain (reduced), output firing pattern (from tonic to phasic) and rate-level functions (from non-monotonic to monotonically increasing). The results suggest that a single cortical network architecture could account for the extended range of experimentally observed response types between the extremes of lateral inhibitory versus co-tuned configurations.     

Dependence of the mouse inferior colliculus neurons activity on position and direction of movement of the spectral contrast

Response variability of the single neurons of the inferior colliculus of mouse (Mus musculus) to series of noise bands and of notch noises with regular 1/12 octave steps of the band/notch center frequency and width of noise band/notch 1/3 octave, was studied. Neurons with strong inhibitory influence in excitatory response area (inhibitory-dominated) show low impulse activity when noise band exceeded excitatory response area. Spectral contrasts crossing the center of excitatory response area (at CF or nearly CF) were found to be the most efficient stimuli for such neurons. Neuron responses to spectral contrasts derived both from noise band and noise notch were identical. Approaching of inhibitory and excitatory inputs is expected to sharpen the auditory neurons frequency tuning to position of spectral contrasts, similar to neuronal processing in visual system. Neuron selectivity to the direction of spectral contrasts movement was determined in neuron response differences when the noise band or notch shifted from excitatory area to inhibitory areas as compared with shift in the opposite direction. Functional role of contrast mechanism for sound localization on the base spectral cues related to external ear transfer characteristics is discussed.     

Spectrotemporal Response Properties of Core Auditory Cortex Neurons in Awake Monkey

So far, most studies of core auditory cortex (AC) have characterized the spectral and temporal tuning properties of cells in non-awake, anesthetized preparations. As experiments in awake animals are scarce, we here used dynamic spectral-temporal broadband ripples to study the properties of the spectrotemporal receptive fields (STRFs) of AC cells in awake monkeys. We show that AC neurons were typically most sensitive to low ripple densities (spectral) and low velocities (temporal), and that most cells were not selective for a particular spectrotemporal sweep direction. A substantial proportion of neurons preferred amplitude-modulated sounds (at zero ripple density) to dynamic ripples (at non-zero densities). The vast majority (>93%) of modulation transfer functions were separable with respect to spectral and temporal modulations, indicating that time and spectrum are independently processed in AC neurons. We also analyzed the linear predictability of AC responses to natural vocalizations on the basis of the STRF. We discuss our findings in the light of results obtained from the monkey midbrain inferior colliculus by comparing the spectrotemporal tuning properties and linear predictability of these two important auditory stages.     

Organizing principles of spectro-temporal encoding in the avian primary auditory area field L

The organization of postthalamic auditory areas remains unclear in many respects. Using a stimulus based on properties of natural sounds, we mapped spectro-temporal receptive fields (STRFs) of neurons in the primary auditory area field L of unanesthetized zebra finches. Cells were sensitive to only a subset of possible acoustic features: nearly all neurons were narrowly tuned along the spectral dimension, the temporal dimension, or both; broadly tuned and strongly orientation-sensitive cells were rare. At high stimulus intensities, neurons were sensitive to differences in sound energy along their preferred dimension, while at lower intensities, neurons behaved more like simple detectors. Finally, we found a systematic relationship between neurons' STRFs, their electrophysiological properties, and their location in field L input or output layers. These data suggest that spectral and temporal processing are segregated within field L, and provide a unifying account of how field L response properties depend on stimulus intensity.     

Electrophysiology and anatomy of medulla interneurons in the optic lobe of the cockroach,Periplaneta americana

1. Medulla interneurons of the optic lobe of P. americana were studied to determine their spectral properties. These neurons exhibited tonic firing which changed with monochromatic broadfield illumination of the ipsilateral eye. The response patterns of these neurons were analyzed by inferring their relation to the ultraviolet (UV) and green (G) photoreceptor groups of the eye. Their anatomy was described after injection of Lucifer yellow. 2. Broadband neurons received either excitatory or inhibitory input from both UV and G receptors. These neurons were not strictly sensitive to luminosity levels and had large cell bodies in the central rind of the medulla and wide dendritic arbors in the medulla neuropil. 3. Narrow band neurons received input from predominantly one receptor type. Their spectral sensitivity curves were more finely tuned than those of the primary receptors presumably due to neural interactions within the optic lobe. 4. Color opponent neurons were inhibited by UV and excited by G inputs in their sustained response. Under certain conditions, some of these neurons also showed G inhibition. These neurons suggested the presence of a subsystem involved in color vision. 5. Broadband, narrow band and color opponent properties were seen in some single neurons when tested over a 5-6 log unit range of intensity. The responses of some of these neurons changed when stimulus duration was increased. These findings indicated that functional classification for these neurons was dependent on stimulus intensity and duration. 6. Polarizational sensitivity was tested in preliminary experiments. Two neurons responded to the movement and direction of polarized light.     

Differential parallel processing of olfactory information in the honeybee, Apis mellifera L.

Two distinct neuronal pathways connect the first olfactory neuropil, the antennal lobe, with higher integration areas, such as the mushroom bodies, via antennal lobe projection neurons. Intracellular recordings were used to address the question whether neuroanatomical features affect odor-coding properties. We found that neurons in the median antennocerebral tract code odors by latency differences or specific inhibitory phases in combination with excitatory phases, have a more specific activity profile for different odors and convey the information with a delay. The neurons of the lateral antennocerebral tract code odors by spike rate differences, have a broader activity profile for different odors, and convey the information quickly. Thus, rather preliminary information about the olfactory stimulus first reaches the mushroom bodies and the lateral horn via neurons of the lateral antennocerebral tract and subsequently odor information becomes more specified by activities of neurons of the median antennocerebral tract. We conclude that this neuroanatomical feature is not related to the distinction between different odors, but rather reflects a dual coding of the same odor stimuli by two different neuronal strategies focusing different properties of the same stimulus.     

小鼠初级听皮质神经元的强度调谐特性与机制分析

强度是声音的基本参数之一,听神经元的强度调谐在听觉信息处理方面具有重要意义．以往研究发现γ-氨基丁酸(γ-aminobutyric acid, GABA)能抑制性输入在强度调谐的形成过程中起重要作用,但对抑制性输入与局部神经回路之间的关系并不清楚．本实验通过在体细胞外电生理记录和神经药理学方法,分析了小鼠初级听皮质神经元的强度调谐特性,结果显示：单调型神经元在声刺激强度自中等强度增高时潜伏期缩短(P < 0.05)且发放持续时间延长(P < 0.05),非单调型神经元在声刺激强度自最佳强度增高时潜伏期不变且发放持续时间缩短(P < 0.01)．注射GABA能阻断剂荷包牡丹碱(bicuculline, Bic)后,39.3%的神经元强度调谐类型不变,42.9%的神经元非单调性减弱,17.9%的神经元非单调性增强．表明GABA能抑制并非是形成非单调性的唯一因素,兴奋性输入本身的非单调性和高阈值非GABA能抑制的激活也可能在其中发挥作用．推测由兴奋性和抑制性输入所构成的局部神经功能回路及其整合决定了听皮质神经元的强度调谐特性．     

Lateral sharpening of cortical frequency tuning by approximately balanced inhibition

Cortical inhibition plays an important role in shaping neuronal processing. The underlying synaptic mechanisms remain controversial. Here, in vivo whole-cell recordings from neurons in the rat primary auditory cortex revealed that the frequency tuning curve of inhibitory input was broader than that of excitatory input. This results in relatively stronger inhibition in frequency domains flanking the preferred frequencies of the cell and a significant sharpening of the frequency tuning of membrane responses. The less selective inhibition can be attributed to a broader bandwidth and lower threshold of spike tonal receptive field of fast-spike inhibitory neurons than nearby excitatory neurons, although both types of neurons receive similar ranges of excitatory input and are organized into the same tonotopic map. Thus, the balance between excitation and inhibition is only approximate, and intracortical inhibition with high sensitivity and low selectivity can laterally sharpen the frequency tuning of neurons, ensuring their highly selective representation.     

脑电事件相关去同步化和同步化的神经元群模型

利用基于丘脑-皮层网络的神经元群模型,研究被试者在某种认知状态下脑功能区的连接状态。模型包括三个模块,分别对应脑电头皮电极C3、Cz、C4记录的三个皮质区。模型外部输入包括用高斯白噪声表示的上行传入感受器信号、用直流偏移表示的皮质对丘脑的兴奋性输入、用指数衰减表示的来自脑千和前脑基底神经元的调制信号。模型输出的兴奋性神经元群的平均膜电位反映脑电记录的局部电位。改变模型输入,进行多次仿真试验并进行线性和非线性分析。研究结果显示：仿真输出信号的alpha频带功率谱有与实际脑机接口实验一致的事件相关去同步化和同步化现象;模型中功能相近的区域间有更强的耦合,随着耦合强度的增加,输出信号间的相关性和同步性均增加。     

锐化蝙蝠听皮层神经元频率调谐的柱特征

用双声刺激和多管电极方法在 6只大棕蝠 (bigbrownbat,Eptesicusfuscus)的 98个神经元上研究了锐化 (sharpening)蝙蝠听皮层 (primaryauditorycortex ,AC)神经元频率调谐的柱特征。结果发现 ,电极直插在 1个电极通道内连续记录到多个神经元时 ,它们锐化频率调谐的抑制性调谐曲线或抑制区基本相似。电极与AC表面呈 45°斜向推入使其跨越多个功能柱时 ,可观察到锐化频率调谐的抑制区构成也随电极进入不同的功能柱而发生相应的改变。两种不同的电极插入方式均证明锐化AC神经元频率调谐的神经抑制呈柱状组构。这些神经元组合起来排列在同一听觉功能柱内 ,构成AC频率分析的基本功能组构单位“微频率处理器”。实验中还观察到多峰频率调谐曲线神经元 ,它们在声通讯和声定位中不同波谱区域的时间匹配中起作用。此外 ,也有理由认为多峰调谐神经元亦被用于作为复杂波谱信息的“高级调谐预处理器” ,从而极大地提高了神经元对频率分析的能力。为研究锐化频率调谐的神经抑制机制 ,用多管电极电泳γ -氨基丁酸 (γ aminobutyricacid ,GA BA)能a受体拮抗剂荷包牡丹碱 (bicuculline ,Bic)至所记录的神经元 ,发现能大部分或几乎全部取消抑制区 ,从而表明在正常情况下GABA能抑制参与构成锐化AC神经元频率调谐的抑制区 ,     

Balanced Excitatory and Inhibitory Synaptic Currents Promote Efficient Coding and Metabolic Efficiency

A balance between excitatory and inhibitory synaptic currents is thought to be important for several aspects of information processing in cortical neurons in vivo, including gain control, bandwidth and receptive field structure. These factors will affect the firing rate of cortical neurons and their reliability, with consequences for their information coding and energy consumption. Yet how balanced synaptic currents contribute to the coding efficiency and energy efficiency of cortical neurons remains unclear. We used single compartment computational models with stochastic voltage-gated ion channels to determine whether synaptic regimes that produce balanced excitatory and inhibitory currents have specific advantages over other input regimes. Specifically, we compared models with only excitatory synaptic inputs to those with equal excitatory and inhibitory conductances, and stronger inhibitory than excitatory conductances (i.e. approximately balanced synaptic currents). Using these models, we show that balanced synaptic currents evoke fewer spikes per second than excitatory inputs alone or equal excitatory and inhibitory conductances. However, spikes evoked by balanced synaptic inputs are more informative (bits/spike), so that spike trains evoked by all three regimes have similar information rates (bits/s). Consequently, because spikes dominate the energy consumption of our computational models, approximately balanced synaptic currents are also more energy efficient than other synaptic regimes. Thus, by producing fewer, more informative spikes approximately balanced synaptic currents in cortical neurons can promote both coding efficiency and energy efficiency.