Ferret Auditory Cortex Research Articles

Temporal-Coherence Induces Binding of Responses to Sound Sequences in Ferret Auditory Cortex.

Binding the attributes of a sensory source is necessary to perceive it as a unified entity, one that can be attended to and extracted from its surrounding scene. In auditory perception, this is the essence of the cocktail party problem in which a listener segregates one speaker from a mixture of voices, or a musical stream from simultaneous others. It is postulated that coherence of the temporal modulations of a source's features is necessary to bind them. The focus of this study is on the role of temporal-coherence in binding and segregation, and specifically as evidenced by the neural correlates of rapid plasticity that enhance cortical responses among synchronized neurons, while suppressing them among asynchronized ones. In a first experiment, we find that attention to a sound sequence rapidly binds it to other coherent sequences while suppressing nearby incoherent sequences, thus enhancing the contrast between the two groups. In a second experiment, a sequence of synchronized multi-tone complexes, embedded in a cloud of randomly dispersed background of desynchronized tones, perceptually and neurally pops-out after a fraction of a second highlighting the binding among its coherent tones against the incoherent background. These findings demonstrate the role of temporal-coherence in binding and segregation.

Reversible Inactivation of Ferret Auditory Cortex Impairs Spatial and Nonspatial Hearing.

A key question in auditory neuroscience is to what extent are brain regions functionally specialized for processing specific sound features, such as location and identity. In auditory cortex, correlations between neural activity and sounds support both the specialization of distinct cortical subfields, and encoding of multiple sound features within individual cortical areas. However, few studies have tested the contribution of auditory cortex to hearing in multiple contexts. Here we determined the role of ferret primary auditory cortex in both spatial and nonspatial hearing by reversibly inactivating the middle ectosylvian gyrus during behavior using cooling (n = 2 females) or optogenetics (n = 1 female). Optogenetic experiments used the mDLx promoter to express Channelrhodopsin-2 in GABAergic interneurons, and we confirmed both viral expression (n = 2 females) and light-driven suppression of spiking activity in auditory cortex, recorded using Neuropixels under anesthesia (n = 465 units from 2 additional untrained female ferrets). Cortical inactivation via cooling or optogenetics impaired vowel discrimination in colocated noise. Ferrets implanted with cooling loops were tested in additional conditions that revealed no deficit when identifying vowels in clean conditions, or when the temporally coincident vowel and noise were spatially separated by 180 degrees. These animals did, however, show impaired sound localization when inactivating the same auditory cortical region implicated in vowel discrimination in noise. Our results demonstrate that, as a brain region showing mixed selectivity for spatial and nonspatial features of sound, primary auditory cortex contributes to multiple forms of hearing.SIGNIFICANCE STATEMENT Neurons in primary auditory cortex are often sensitive to the location and identity of sounds. Here we inactivated auditory cortex during spatial and nonspatial listening tasks using cooling, or optogenetics. Auditory cortical inactivation impaired multiple behaviors, demonstrating a role in both the analysis of sound location and identity and confirming a functional contribution of mixed selectivity observed in neural activity. Parallel optogenetic experiments in two additional untrained ferrets linked behavior to physiology by demonstrating that expression of Channelrhodopsin-2 permitted rapid light-driven suppression of auditory cortical activity recorded under anesthesia.

Distinct higher-order representations of natural sounds in human and ferret auditory cortex.

Little is known about how neural representations of natural sounds differ across species. For example, speech and music play a unique role in human hearing, yet it is unclear how auditory representations of speech and music differ between humans and other animals. Using functional ultrasound imaging, we measured responses in ferrets to a set of natural and spectrotemporally matched synthetic sounds previously tested in humans. Ferrets showed similar lower-level frequency and modulation tuning to that observed in humans. But while humans showed substantially larger responses to natural vs. synthetic speech and music in non-primary regions, ferret responses to natural and synthetic sounds were closely matched throughout primary and non-primary auditory cortex, even when tested with ferret vocalizations. This finding reveals that auditory representations in humans and ferrets diverge sharply at late stages of cortical processing, potentially driven by higher-order processing demands in speech and music.

Dynamics and Hierarchical Encoding of Non-compact Acoustic Categories in Auditory and Frontal Cortex.

Categorical perception is a fundamental cognitive function enabling animals to flexibly assign sounds into behaviorally relevant categories. This study investigates the nature of acoustic category representations, their emergence in an ascending series of ferret auditory and frontal cortical fields, and the dynamics of this representation during passive listening to task-relevant stimuli and during active retrieval from memory while engaging in learned categorization tasks. Ferrets were trained on two auditory Go-NoGo categorization tasks to discriminate two non-compact sound categories (composed of tones or amplitude-modulated noise). Neuronal responses became progressively more categorical in higher cortical fields, especially during task performance. The dynamics of the categorical responses exhibited a cascading top-down modulation pattern that began earliest in the frontal cortex and subsequently flowed downstream to the secondary auditory cortex, followed by the primary auditory cortex. In a subpopulation of neurons, categorical responses persisted even during the passive listening condition, demonstrating memory for task categories and their enhanced categorical boundaries.

State-dependent encoding of sound and behavioral meaning in a tertiary region of the ferret auditory cortex.

In higher sensory cortices, there is a gradual transformation from sensation to perception and action. In the auditory system, this transformation is revealed by responses in the rostral Ventral Posterior field (VPr), a tertiary area in ferret auditory cortex, which shows long-term learning in trained compared to naïve animals, arising from selectively enhanced responses to behaviorally relevant target stimuli. This enhanced representation is further amplified during active performance of spectral or temporal auditory discrimination tasks. VPr also shows sustained short-term memory activity after target stimulus offset, correlated with task-response timing and action. These task-related changes in auditory filter properties enable VPr neurons to quickly and nimbly switch between different responses to the same acoustic stimuli, reflecting either spectrotemporal properties, timing or behavioral meaning of the sound. Furthermore, they demonstrate an interaction between dynamics of long-term learning and short-term attention as incoming sound is selectively attended, recognized and translated into action.

Acute Inactivation of Primary Auditory Cortex Causes a Sound Localisation Deficit in Ferrets.

The objective of this study was to demonstrate the efficacy of acute inactivation of brain areas by cooling in the behaving ferret and to demonstrate that cooling auditory cortex produced a localisation deficit that was specific to auditory stimuli. The effect of cooling on neural activity was measured in anesthetized ferret cortex. The behavioural effect of cooling was determined in a benchmark sound localisation task in which inactivation of primary auditory cortex (A1) is known to impair performance. Cooling strongly suppressed the spontaneous and stimulus-evoked firing rates of cortical neurons when the cooling loop was held at temperatures below 10°C, and this suppression was reversed when the cortical temperature recovered. Cooling of ferret auditory cortex during behavioural testing impaired sound localisation performance, with unilateral cooling producing selective deficits in the hemifield contralateral to cooling, and bilateral cooling producing deficits on both sides of space. The deficit in sound localisation induced by inactivation of A1 was not caused by motivational or locomotor changes since inactivation of A1 did not affect localisation of visual stimuli in the same context.

Incorporating Midbrain Adaptation to Mean Sound Level Improves Models of Auditory Cortical Processing.

An ability to accurately predict how sensory neurons respond to novel stimuli is critical if we are to fully characterize their response properties. Attempts to model these responses have had a distinguished history, but it has proven difficult to improve their predictive power significantly beyond that of simple, mostly linear receptive field models. Here we show that auditory cortex receptive field models benefit from a nonlinear preprocessing stage that replicates known adaptation properties of the auditory midbrain. This improves their predictive power across a wide range of stimuli but keeps model complexity low as it introduces no new free parameters. Incorporating the adaptive coding properties of neurons will likely improve receptive field models in other sensory modalities too.

Reconstruction of audio waveforms from spike trains of artificial cochlea models.

Spiking cochlea models describe the analog processing and spike generation process within the biological cochlea. Reconstructing the audio input from the artificial cochlea spikes is therefore useful for understanding the fidelity of the information preserved in the spikes. The reconstruction process is challenging particularly for spikes from the mixed signal (analog/digital) integrated circuit (IC) cochleas because of multiple non-linearities in the model and the additional variance caused by random transistor mismatch. This work proposes an offline method for reconstructing the audio input from spike responses of both a particular spike-based hardware model called the AEREAR2 cochlea and an equivalent software cochlea model. This method was previously used to reconstruct the auditory stimulus based on the peri-stimulus histogram of spike responses recorded in the ferret auditory cortex. The reconstructed audio from the hardware cochlea is evaluated against an analogous software model using objective measures of speech quality and intelligibility; and further tested in a word recognition task. The reconstructed audio under low signal-to-noise (SNR) conditions (SNR < –5 dB) gives a better classification performance than the original SNR input in this word recognition task.

Cortico-Cortical Connectivity Within Ferret Auditory Cortex.

ABSTRACTDespite numerous studies of auditory cortical processing in the ferret (Mustela putorius), very little is known about the connections between the different regions of the auditory cortex that have been characterized cytoarchitectonically and physiologically. We examined the distribution of retrograde and anterograde labeling after injecting tracers into one or more regions of ferret auditory cortex. Injections of different tracers at frequency‐matched locations in the core areas, the primary auditory cortex (A1) and anterior auditory field (AAF), of the same animal revealed the presence of reciprocal connections with overlapping projections to and from discrete regions within the posterior pseudosylvian and suprasylvian fields (PPF and PSF), suggesting that these connections are frequency specific. In contrast, projections from the primary areas to the anterior dorsal field (ADF) on the anterior ectosylvian gyrus were scattered and non‐overlapping, consistent with the non‐tonotopic organization of this field. The relative strength of the projections originating in each of the primary fields differed, with A1 predominantly targeting the posterior bank fields PPF and PSF, which in turn project to the ventral posterior field, whereas AAF projects more heavily to the ADF, which then projects to the anteroventral field and the pseudosylvian sulcal cortex. These findings suggest that parallel anterior and posterior processing networks may exist, although the connections between different areas often overlap and interactions were present at all levels. J. Comp. Neurol. 523:2187–2210, 2015. © 2015 Wiley Periodicals, Inc.

Cross-modal plasticity results in increased inhibition in primary auditory cortical areas.

Loss of sensory input from peripheral organ damage, sensory deprivation, or brain damage can result in adaptive or maladaptive changes in sensory cortex. In previous research, we found that auditory cortical tuning and tonotopy were impaired by cross-modal invasion of visual inputs. Sensory deprivation is typically associated with a loss of inhibition. To determine whether inhibitory plasticity is responsible for this process, we measured pre- and postsynaptic changes in inhibitory connectivity in ferret auditory cortex (AC) after cross-modal plasticity. We found that blocking GABAA receptors increased responsiveness and broadened sound frequency tuning in the cross-modal group more than in the normal group. Furthermore, expression levels of glutamic acid decarboxylase (GAD) protein were increased in the cross-modal group. We also found that blocking inhibition unmasked visual responses of some auditory neurons in cross-modal AC. Overall, our data suggest a role for increased inhibition in reducing the effectiveness of the abnormal visual inputs and argue that decreased inhibition is not responsible for compromised auditory cortical function after cross-modal invasion. Our findings imply that inhibitory plasticity may play a role in reorganizing sensory cortex after cross-modal invasion, suggesting clinical strategies for recovery after brain injury or sensory deprivation.

Spectrotemporal Contrast Kernels for Neurons in Primary Auditory Cortex

Auditory neurons are often described in terms of their spectrotemporal receptive fields (STRFs). These map the relationship between features of the sound spectrogram and firing rates of neurons. Recently, we showed that neurons in the primary fields of the ferret auditory cortex are also subject to gain control: when sounds undergo smaller fluctuations in their level over time, the neurons become more sensitive to small-level changes (Rabinowitz et al., 2011). Just as STRFs measure the spectrotemporal features of a sound that lead to changes in the firing rates of neurons, in this study, we sought to estimate the spectrotemporal regions in which sound statistics lead to changes in the gain of neurons. We designed a set of stimuli with complex contrast profiles to characterize these regions. This allowed us to estimate the STRFs of cortical neurons alongside a set of spectrotemporal contrast kernels. We find that these two sets of integration windows match up: the extent to which a stimulus feature causes the firing rate of a neuron to change is strongly correlated with the extent to which the contrast of that feature modulates the gain of the neuron. Adding contrast kernels to STRF models also yields considerable improvements in the ability to capture and predict how auditory cortical neurons respond to statistically complex sounds.

Multiplexed and Robust Representations of Sound Features in Auditory Cortex

We can recognize the melody of a familiar song when it is played on different musical instruments. Similarly, an animal must be able to recognize a warning call whether the caller has a high-pitched female or a lower-pitched male voice, and whether they are sitting in a tree to the left or right. This type of perceptual invariance to "nuisance" parameters comes easily to listeners, but it is unknown whether or how such robust representations of sounds are formed at the level of sensory cortex. In this study, we investigate whether neurons in both core and belt areas of ferret auditory cortex can robustly represent the pitch, formant frequencies, or azimuthal location of artificial vowel sounds while the other two attributes vary. We found that the spike rates of the majority of cortical neurons that are driven by artificial vowels carry robust representations of these features, but the most informative temporal response windows differ from neuron to neuron and across five auditory cortical fields. Furthermore, individual neurons can represent multiple features of sounds unambiguously by independently modulating their spike rates within distinct time windows. Such multiplexing may be critical to identifying sounds that vary along more than one perceptual dimension. Finally, we observed that formant information is encoded in cortex earlier than pitch information, and we show that this time course matches ferrets' behavioral reaction time differences on a change detection task.

Contrast Gain Control in Auditory Cortex

SummaryThe auditory system must represent sounds with a wide range of statistical properties. One important property is the spectrotemporal contrast in the acoustic environment: the variation in sound pressure in each frequency band, relative to the mean pressure. We show that neurons in ferret auditory cortex rescale their gain to partially compensate for the spectrotemporal contrast of recent stimulation. When contrast is low, neurons increase their gain, becoming more sensitive to small changes in the stimulus, although the effectiveness of contrast gain control is reduced at low mean levels. Gain is primarily determined by contrast near each neuron's preferred frequency, but there is also a contribution from contrast in more distant frequency bands. Neural responses are modulated by contrast over timescales of ∼100 ms. By using contrast gain control to expand or compress the representation of its inputs, the auditory system may be seeking an efficient coding of natural sounds.

Brief sounds evoke prolonged responses in anesthetized ferret auditory cortex.

Neurons in the auditory cortex of anesthetized animals are generally considered to generate phasic responses to simple stimuli such as tones or noise bursts. In this paper, we show that under ketamine/medetomidine anesthesia, neurons in ferret auditory cortex usually exhibit complex sustained responses. We presented 100-ms broad-band noise bursts at a range of interaural level differences (ILDs) and average binaural levels (ABLs), and used extracellular electrodes to monitor evoked activity over 700 ms poststimulus onset. We estimated the degree of randomness (noise) in the response functions of individual neurons over poststimulus time; we found that neural activity was significantly modulated by sound for up to ∼500 ms following stimulus offset. Pooling data from all neurons, we found that spiking activity carries significant information about stimulus identity over this same time period. However, information about ILD decayed much more quickly over time compared with information about ABL. In addition, ILD and ABL are coded independently by the neural population even though this is not the case at individual neurons. Though most neurons responded more strongly to ILDs corresponding to the opposite side of space, as a population, they were equally informative about both contra- and ipsilateral stimuli.

Visual influences on ferret auditory cortex

Multisensory neurons are now known to be widespread in low-level regions of the cortex usually thought of as being responsible for modality-specific processing. The auditory cortex provides a particularly striking example of this, exhibiting responses to both visual and somatosensory stimulation. Single-neuron recording studies in ferrets have shown that each of auditory fields that have been characterized using physiological and anatomical criteria also receives visual inputs, with the incidence of visually-sensitive neurons ranging from 15% to 20% in the primary areas to around 50% or more in higher-level areas. Although some neurons exhibit spiking responses to visual stimulation, these inputs often have subthreshold influences that modulate the responses of the cortical neurons to sound. Insights into the possible role played by the visual inputs can be obtained by examining their sources of origin and the way in which they alter the processing capabilities of neurons in the auditory cortex. These studies suggest that one of the functions of the visual input to auditory cortex is to sharpen the relatively imprecise spatial coding typically found there. Because the extent to which this happens varies between cortical fields, the investigation of multisensory interactions can also help in understanding their relative contributions to auditory perception.

Adult deafness induces somatosensory conversion of ferret auditory cortex

In response to early or developmental lesions, responsiveness of sensory cortex can be converted from the deprived modality to that of the remaining sensory systems. However, little is known about capacity of the adult cortex for cross-modal reorganization. The present study examined the auditory cortices of animals deafened as adults, and observed an extensive somatosensory conversion within as little as 16 days after deafening. These results demonstrate that cortical cross-modal reorganization can occur after the period of sensory system maturation.

Interdependent encoding of pitch, timbre, and spatial location in auditory cortex.

Because we can perceive the pitch, timbre, and spatial location of a sound source independently, it seems natural to suppose that cortical processing of sounds might separate out spatial from nonspatial attributes. Indeed, recent studies support the existence of anatomically segregated "what" and "where" cortical processing streams. However, few attempts have been made to measure the responses of individual neurons in different cortical fields to sounds that vary simultaneously across spatial and nonspatial dimensions. We recorded responses to artificial vowels presented in virtual acoustic space to investigate the representations of pitch, timbre, and sound source azimuth in both core and belt areas of ferret auditory cortex. A variance decomposition technique was used to quantify the way in which altering each parameter changed neural responses. Most units were sensitive to two or more of these stimulus attributes. Although indicating that neural encoding of pitch, location, and timbre cues is distributed across auditory cortex, significant differences in average neuronal sensitivity were observed across cortical areas and depths, which could form the basis for the segregation of spatial and nonspatial cues at higher cortical levels. Some units exhibited significant nonlinear interactions between particular combinations of pitch, timbre, and azimuth. These interactions were most pronounced for pitch and timbre and were less commonly observed between spatial and nonspatial attributes. Such nonlinearities were most prevalent in primary auditory cortex, although they tended to be small compared with stimulus main effects.

Responses of Auditory Cortex to Complex Stimuli: Functional Organization Revealed Using Intrinsic Optical Signals

We used optical imaging of intrinsic signals to study the large-scale organization of ferret auditory cortex in response to complex sounds. Cortical responses were collected during continuous stimulation by sequences of sounds with varying frequency, period, or interaural level differences. We used a set of stimuli that differ in spectral structure, but have the same periodicity and therefore evoke the same pitch percept (click trains, sinusoidally amplitude modulated tones, and iterated ripple noise). These stimuli failed to reveal a consistent periodotopic map across the auditory fields imaged. Rather, gradients of period sensitivity differed for the different types of periodic stimuli. Binaural interactions were studied both with single contralateral, ipsilateral, and diotic broadband noise bursts and with sequences of broadband noise bursts with varying level presented contralaterally, ipsilaterally, or in opposite phase to both ears. Contralateral responses were generally largest and ipsilateral responses were smallest when using single noise bursts, but the extent of the activated area was large and comparable in all three aural configurations. Modulating the amplitude in counter phase to the two ears generally produced weaker modulation of the optical signals than the modulation produced by the monaural stimuli. These results suggest that binaural interactions seen in cortex are most likely predominantly due to subcortical processing. Thus our optical imaging data do not support the theory that the primary or nonprimary cortical fields imaged are topographically organized to form consistent maps of systematically varying sensitivity either to stimulus pitch or to simple binaural properties of the acoustic stimuli.

Binaural-Level Functions in Ferret Auditory Cortex: Evidence for a Continuous Distribution of Response Properties

Many previous studies have subdivided auditory neurons into a number of physiological classes according to various criteria applied to their binaural response properties. However, it is often unclear whether such classifications represent discrete classes of neurons or whether they merely reflect a potentially convenient but ultimately arbitrary partitioning of a continuous underlying distribution of response properties. In this study we recorded the binaural response properties of 310 units in the auditory cortex of anesthetized ferrets, using an extensive range of interaural level differences (ILDs) and average binaural levels (ABLs). Most recordings were from primary auditory fields on the middle ectosylvian gyrus and from neurons with characteristic frequencies >5 kHz. We used simple multivariate statistics to quantify a fundamental coding feature: the shapes of the binaural response functions. The shapes of all 310 binaural response surfaces were represented as points in a five-dimensional principal component space. This space captured the underlying shape of all the binaural response surfaces. The distribution of binaural level functions was not homogeneous because some shapes were more common than others. Despite this, clustering validation techniques revealed no evidence for the existence of discrete, or partially overlapping, clusters that could serve as a basis for an objective classification of binaural-level functions. We also examined the gradients of the response functions for the population of units; these gradients were greatest near the midline, which is consistent with free-field data showing that cortical neurons are most sensitive to changes in stimulus location in this region of space.

The Ferret Auditory Cortex: Descending Projections to the Inferior Colliculus

Descending corticofugal projections are thought to play a critical role in shaping the responses of subcortical neurons. Here, we examine the origins and targets of ferret auditory corticocollicular projections. We show that the ectosylvian gyrus (EG), where the auditory cortex is located, can be subdivided into middle, anterior, and posterior regions according to the pattern of cytochrome oxidase staining and immunoreactivity for the neurofilament antibody SMI32. Injection of retrograde tracers in the inferior colliculus (IC) labeled large layer V pyramidal cells throughout the EG and adjacent sulci. Each region of the EG has a different pattern of descending projections. Neurons in the primary auditory fields in the middle EG project to the lateral nucleus (LN) of the ipsilateral IC and bilaterally to the dorsal cortex and dorsal part of the central nucleus (CN). The projection to these dorsomedial regions of the IC is predominantly ipsilateral and topographically organized. The secondary cortical fields in the posterior EG target the same midbrain areas but exclude the CN of the IC. A smaller projection to the ipsilateral LN also arises from the anterior EG, which is the only region of auditory cortex to target tegmental areas surrounding the IC, including the superior colliculus, periaqueductal gray, intercollicular tegmentum, and cuneiform nucleus. This pattern of corticocollicular connectivity is consistent with regional differences in physiological properties and provides another basis for subdividing ferret auditory cortex into functionally distinct areas.