Electrophysiology publications

Feedback signals from the primary auditory cortex (A1) can shape the receptive field properties of neurons in the ventral division of the medial geniculate body (MGBv). However, the behavioral significance of corticothalamic modulation is unknown. The aim of this study was to elucidate the role of this descending pathway in the perception of complex sounds. We tested the ability of adult female ferrets to detect the presence of a mistuned harmonic in a complex tone using a positive conditioned go/no-go behavioral paradigm before and after the input from layer VI in A1 to MGBv was bilaterally and selectively eliminated using chromophore-targeted laser photolysis. MGBv neurons were identified by their short latencies and sharp tuning curves. They responded robustly to harmonic complex tones and exhibited an increase in firing rate and temporal pattern changes when one frequency component in the complex tone was mistuned. Injections of fluorescent microbeads conjugated with a light-sensitive chromophore were made in MGBv, and, following retrograde transport to the cortical cell bodies, apoptosis was induced by infrared laser illumination of A1. This resulted in a selective loss of ∼60% of layer VI A1-MGBv neurons. After the lesion, mistuning detection was impaired, as indicated by decreased d' values, a shift of the psychometric curves toward higher mistuning values, and increased thresholds, whereas discrimination performance was unaffected when level cues were also available. Our results suggest that A1-MGBv corticothalamic feedback contributes to the detection of harmonicity, one of the most important grouping cues in the perception of complex sounds.SIGNIFICANCE STATEMENT Perception of a complex auditory scene is based on the ability of the brain to group those sound components that belong to the same source and to segregate them from those belonging to different sources. Because two people talking simultaneously may differ in their voice pitch, perceiving the harmonic structure of sounds is very important for auditory scene analysis. Here we demonstrate mistuning sensitivity in the thalamus and that feedback from the primary auditory cortex is required for the normal ability of ferrets to detect a mistuned harmonic within a complex sound. These results provide novel insight into the function of descending sensory pathways in the brain and suggest that this corticothalamic circuit plays an important role in scene analysis.

Tonotopic map plasticity in the adult auditory cortex (AC) is a well established and oft-cited measure of auditory associative learning in classical conditioning paradigms. However, its necessity as an enduring memory trace has been debated, especially given a recent finding that the areal expansion of core AC tuned to a newly relevant frequency range may arise only transiently to support auditory learning. This has been reinforced by an ethological paradigm showing that map expansion is not observed for ultrasonic vocalizations (USVs) or for ultrasound frequencies in postweaning dams for whom USVs emitted by pups acquire behavioral relevance. However, whether transient expansion occurs during maternal experience is not known, and could help to reveal the generality of cortical map expansion as a correlate for auditory learning. We thus mapped the auditory cortices of maternal mice at postnatal time points surrounding the peak in pup USV emission, but found no evidence of frequency map expansion for the behaviorally relevant high ultrasound range in AC. Instead, regions tuned to low frequencies outside of the ultrasound range show progressively greater suppression of activity in response to the playback of ultrasounds or pup USVs for maternally experienced animals assessed at their pups’ postnatal day 9 (P9) to P10, or postweaning. This provides new evidence for a lateral-band suppression mechanism elicited by behaviorally meaningful USVs, likely enhancing their population-level signal-to-noise ratio. These results demonstrate that tonotopic map enlargement has limits as a construct for conceptualizing how experience leaves neural memory traces within sensory cortex in the context of ethological auditory learning.

Local field potentials (LFPs) and spikes (SPKs) sampled at the thalamocortical recipient layers represent the inputs from the thalamus and outputs to other layers. Previous studies have shown that SPK‐constructed receptive fields (RF SPK ) of cortical neurons are much smaller than LFP‐constructed RFs (RF LFP ). The difference in cortical RF LFP and RF SPK is therefore a plausible indication of local networking. The presence of a boarder RF LFP appears due to contamination, to some degree, from remote sites. Our studies of the mouse primary auditory cortex show that the best frequencies and minimum thresholds of RF SPK and RF LFP were similar. We also observed that the RF LFP area was only slightly larger than the RF SPK area, a very different finding from previous reports. The bandwidth of RF LFP was slightly broader than that of RF SPK at all levels. These data do not support the explanation that bioelectrical signals from distant sites impact on cortical LFP through volume conduction. That the cortical LFP represents a local event is further supported by comparisons of RF SPK and RF LFP after cortical inhibition by muscimol and cortical disinhibition by bicuculine. We conclude that the difference between RF SPK (output of cortical neurons) and RF LFP (input of cortical neurons) results from intracortical processing, including cortical lateral inhibition and excitation.

Despite 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.

The interplay of cortical excitation and inhibition is a fundamental feature of cortical information processing. Excitation and inhibition in single cortical neurons are balanced in their response to optimal sensory stimulation due to thalamocortical feedforward microcircuitry. It is unclear whether the balance between cortical excitation and inhibition is maintained at the threshold stimulus level. Using in vivo whole-cell patch-clamp recording of thalamocortical recipient neurons in the primary auditory cortex of mice, we examined the tone-evoked excitatory and inhibitory postsynaptic currents at threshold levels. Similar to previous reports, tone induced excitatory postsynaptic currents when the membrane potentials were held at 70 mV and inhibitory postsynaptic currents when the membrane potentials were held at 0 mV on single cortical neurons. This coupled excitation and inhibition is not demonstrated when threshold-level tone stimuli are presented. In most cases, tone induced only excitatory postsynaptic current. The best frequencies of excitatory and inhibitory responses were often different and thresholds of inhibitory responses were mostly higher than those of excitatory responses. Our data suggest that the excitatory and inhibitory inputs to single cortical neurons are imbalanced at the threshold level. This imbalance may result from the inherent dynamics of thalamocortical feedforward microcircuitry.

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.

It is generally thought that background noise can mask auditory information. However, how the noise specifically transforms neuronal auditory processing in a level-dependent manner remains to be carefully determined. Here, with in vivo loose-patch cell-attached recordings in layer 4 of the rat primary auditory cortex (A1), we systematically examined how continuous wideband noise of different levels affected receptive field properties of individual neurons. We found that the background noise, when above a certain critical/effective level, resulted in an elevation of intensity threshold for tone-evoked responses. This increase of threshold was linearly dependent on the noise intensity above the critical level. As such, the tonal receptive field (TRF) of individual neurons was translated upward as an entirety toward high intensities along the intensity domain. This resulted in preserved preferred characteristic frequency (CF) and the overall shape of TRF, but reduced frequency responding range and an enhanced frequency selectivity for the same stimulus intensity. Such translational effects on intensity threshold were observed in both excitatory and fast-spiking inhibitory neurons, as well as in both monotonic and nonmonotonic (intensity-tuned) A1 neurons. Our results suggest that in a noise background, fundamental auditory representations are modulated through a background level-dependent linear shifting along intensity domain, which is equivalent to reducing stimulus intensity.

The primary auditory cortex (AI) modulates the sound information processing in the lemniscal subcortical nuclei, including the anteroventral cochlear nucleus (AVCN), in a frequency-specific manner. The dorsal cochlear nucleus (DCN) is a non-lemniscal subcortical nucleus but it is tonotopically organized like the AVCN. However, it remains unclear how the AI modulates the sound information processing in the DCN. This study examined the impact of focal electrical stimulation of AI on the auditory responses of the DCN neurons in mice. We found that the electrical stimulation induced significant changes in the best frequency (BF) of DCN neurons. The changes in the BFs were highly specific to the BF differences between the stimulated AI neurons and the recorded DCN neurons. The DCN BFs shifted higher when the AI BFs were higher than the DCN BFs and the DCN BFs shifted lower when the AI BFs were lower than the DCN BFs. The DCN BFs showed no change when the AI and DCN BFs were similar. Moreover, the BF shifts were linearly correlated to the BF differences. Thus, our data suggest that corticofugal modulation of the DCN is also highly specific to frequency information, similar to the corticofugal modulation of the AVCN. The frequency-specificity of corticofugal modulation does not appear limited to the lemniscal ascending pathway.

Cholinergic inputs to the auditory cortex can modulate sensory processing and regulate stimulus‐specific plasticity according to the behavioural state of the subject. In order to understand how acetylcholine achieves this, it is essential to elucidate the circuitry by which cholinergic inputs influence the cortex. In this study, we described the distribution of cholinergic neurons in the basal forebrain and their inputs to the auditory cortex of the ferret, a species used increasingly in studies of auditory learning and plasticity. Cholinergic neurons in the basal forebrain, visualized by choline acetyltransferase and p75 neurotrophin receptor immunocytochemistry, were distributed through the medial septum, diagonal band of Broca, and nucleus basalis magnocellularis. Epipial tracer deposits and injections of the immunotoxin ME 20.4‐ SAP (monoclonal antibody specific for the p75 neurotrophin receptor conjugated to saporin) in the auditory cortex showed that cholinergic inputs originate almost exclusively in the ipsilateral nucleus basalis. Moreover, tracer injections in the nucleus basalis revealed a pattern of labelled fibres and terminal fields that resembled acetylcholinesterase fibre staining in the auditory cortex, with the heaviest labelling in layers II / III and in the infragranular layers. Labelled fibres with small en‐passant varicosities and simple terminal swellings were observed throughout all auditory cortical regions. The widespread distribution of cholinergic inputs from the nucleus basalis to both primary and higher level areas of the auditory cortex suggests that acetylcholine is likely to be involved in modulating many aspects of auditory processing.

Auditory cortical plasticity can be induced through various approaches. The medial geniculate body (MGB) of the auditory thalamus gates the ascending auditory inputs to the cortex. The thalamocortical system has been proposed to play a critical role in the responses of the auditory cortex (AC). In the present study, we investigated the cellular mechanism of the cortical activity, adopting an in vivo intracellular recording technique, recording from the primary auditory cortex (AI) while presenting an acoustic stimulus to the rat and electrically stimulating its MGB. We found that low-frequency stimuli enhanced the amplitudes of sound-evoked excitatory postsynaptic potentials (EPSPs) in AI neurons, whereas high-frequency stimuli depressed these auditory responses. The degree of this modulation depended on the intensities of the train stimuli as well as the intervals between the electrical stimulations and their paired sound stimulations. These findings may have implications regarding the basic mechanisms of MGB activation of auditory cortical plasticity and cortical signal processing.

Natural auditory scenes such as frog choruses consist of multiple sound sources (i.e., individual vocalizing males) producing sounds that overlap extensively in time and spectrum, often in the presence of other biotic and abiotic background noise. Detection of a signal in such environments is challenging, but it is facilitated when the noise shares common amplitude modulations across a wide frequency range, due to a phenomenon called comodulation masking release (CMR). Here, we examined how properties of the background noise, such as its bandwidth and amplitude modulation, influence the detection threshold of a target sound (pulsed amplitude modulated tones) by single neurons in the frog auditory midbrain. We found that for both modulated and unmodulated masking noise, masking was generally stronger with increasing bandwidth, but it was weakened for the widest bandwidths. Masking was less for modulated noise than for unmodulated noise for all bandwidths. However, responses were heterogeneous, and only for a subpopulation of neurons the detection of the probe was facilitated when the bandwidth of the modulated masker was increased beyond a certain bandwidth - such neurons might contribute to CMR. We observed evidence that suggests that the dips in the noise amplitude are exploited by TS neurons, and observed strong responses to target signals occurring during such dips. However, the interactions between the probe and masker responses were nonlinear, and other mechanisms, e.g., selective suppression of the response to the noise, may also be involved in the masking release.

We have previously shown that neurons in primary auditory cortex (A1) of anaesthetized (ketamine/medetomidine) ferrets respond more strongly and reliably to dynamic stimuli whose statistics follow "natural" 1/f dynamics than to stimuli exhibiting pitch and amplitude modulations that are faster (1/f(0.5)) or slower (1/f(2)) than 1/f. To investigate where along the central auditory pathway this 1/f-modulation tuning arises, we have now characterized responses of neurons in the central nucleus of the inferior colliculus (ICC) and the ventral division of the mediate geniculate nucleus of the thalamus (MGV) to 1/f(γ) distributed stimuli with γ varying between 0.5 and 2.8. We found that, while the great majority of neurons recorded from the ICC showed a strong preference for the most rapidly varying (1/f(0.5) distributed) stimuli, responses from MGV neurons did not exhibit marked or systematic preferences for any particular γ exponent. Only in A1 did a majority of neurons respond with higher firing rates to stimuli in which γ takes values near 1. These results indicate that 1/f tuning emerges at forebrain levels of the ascending auditory pathway.

Background: Cortical neurons implement a high frequency-specific modulation of subcortical nuclei that includes the cochlear nucleus. Anatomical studies show that corticofugal fibers terminating in the auditory thalamus and midbrain are mostly ipsilateral. Differently, corticofugal fibers terminating in the cochlear nucleus are bilateral, which fits to the needs of binaural hearing that improves hearing quality. This leads to our hypothesis that corticofugal modulation of initial neural processing of sound information from the contralateral and ipsilateral ears could be equivalent or coordinated at the first sound processing level. Methodology/principal findings: With the focal electrical stimulation of the auditory cortex and single unit recording, this study examined corticofugal modulation of the ipsilateral cochlear nucleus. The same methods and procedures as described in our previous study of corticofugal modulation of contralateral cochlear nucleus were employed simply for comparison. We found that focal electrical stimulation of cortical neurons induced substantial changes in the response magnitude, response latency and receptive field of ipsilateral cochlear nucleus neurons. Cortical stimulation facilitated auditory response and shortened the response latency of physiologically matched neurons whereas it inhibited auditory response and lengthened the response latency of unmatched neurons. Finally, cortical stimulation shifted the best frequencies of cochlear neurons towards those of stimulated cortical neurons. Conclusion: Our data suggest that cortical neurons enable a high frequency-specific remodelling of sound information processing in the ipsilateral cochlear nucleus in the same manner as that in the contralateral cochlear nucleus.

Sensory systems are known to adapt their coding strategies to the statistics of their environment, but little is still known about the perceptual implications of such adjustments. We investigated how auditory spatial processing adapts to stimulus statistics by presenting human listeners and anesthetized ferrets with noise sequences in which interaural level differences (ILD) rapidly fluctuated according to a Gaussian distribution. The mean of the distribution biased the perceived laterality of a subsequent stimulus, whereas the distribution's variance changed the listeners' spatial sensitivity. The responses of neurons in the inferior colliculus changed in line with these perceptual phenomena. Their ILD preference adjusted to match the stimulus distribution mean, resulting in large shifts in rate-ILD functions, while their gain adapted to the stimulus variance, producing pronounced changes in neural sensitivity. Our findings suggest that processing of auditory space is geared toward emphasizing relative spatial differences rather than the accurate representation of absolute position.

Huia cavitympanum, an endemic Bornean frog, is the first amphibian species known to emit exclusively ultrasonic (i.e., >20 kHz) vocal signals. To test the hypothesis that these frogs use purely ultrasonic vocalizations for intraspecific communication, we performed playback experiments with male frogs in their natural calling sites. We found that the frogs respond with increased calling to broadcasts of conspecific calls containing only ultrasound. The field study was complemented by electrophysiological recordings from the auditory midbrain and by laser Doppler vibrometer measurements of the tympanic membrane's response to acoustic stimulation. These measurements revealed that the frog's auditory system is broadly tuned over high frequencies, with peak sensitivity occurring within the ultrasonic frequency range. Our results demonstrate that H. cavitympanum is the first non-mammalian vertebrate described to communicate with purely ultrasonic acoustic signals. These data suggest that further examination of the similarities and differences in the high-frequency/ultrasonic communication systems of H. cavitympanum and Odorrana tormota, an unrelated frog species that produces and detects ultrasound but does not emit exclusively ultrasonic calls, will afford new insights into the mechanisms underlying vertebrate high-frequency communication.

Background Magnetoencephalography (MEG) has become an increasingly popular technique for non-invasively characterizing neuromagnetic field changes in the brain at a high temporal resolution. To examine the reliability of the MEG signal, we compared magnetic and electrophysiological responses to complex natural stimuli from the same animals. We examined changes in neuromagnetic fields, local field potentials (LFP) and multi-unit activity (MUA) in macaque monkey primary somatosensory cortex that were induced by varying the rate of mechanical stimulation. Stimuli were applied to the fingertips with three inter-stimulus intervals (ISIs): 0.33s, 1s and 2s. Results Signal intensity was inversely related to the rate of stimulation, but to different degrees for each measurement method. The decrease in response at higher stimulation rates was significantly greater for MUA than LFP and MEG data, while no significant difference was observed between LFP and MEG recordings. Furthermore, response latency was the shortest for MUA and the longest for MEG data. Conclusion The MEG signal is an accurate representation of electrophysiological responses to complex natural stimuli. Further, the intensity and latency of the MEG signal were better correlated with the LFP than MUA data suggesting that the MEG signal reflects primarily synaptic currents rather than spiking activity. These differences in latency could be attributed to differences in the extent of spatial summation and/or differential laminar sensitivity.

Recent studies, conducted almost exclusively in primates, have shown that several cortical areas usually associated with modality-specific sensory processing are subject to influences from other senses. Here we demonstrate using single-unit recordings and estimates of mutual information that visual stimuli can influence the activity of units in the auditory cortex of anesthetized ferrets. In many cases, these units were also acoustically responsive and frequently transmitted more information in their spike discharge patterns in response to paired visual-auditory stimulation than when either modality was presented by itself. For each stimulus, this information was conveyed by a combination of spike count and spike timing. Even in primary auditory areas (primary auditory cortex [A1] and anterior auditory field [AAF]), approximately 15% of recorded units were found to have nonauditory input. This proportion increased in the higher level fields that lie ventral to A1/AAF and was highest in the anterior ventral field, where nearly 50% of the units were found to be responsive to visual stimuli only and a further quarter to both visual and auditory stimuli. Within each field, the pure-tone response properties of neurons sensitive to visual stimuli did not differ in any systematic way from those of visually unresponsive neurons. Neural tracer injections revealed direct inputs from visual cortex into auditory cortex, indicating a potential source of origin for the visual responses. Primary visual cortex projects sparsely to A1, whereas higher visual areas innervate auditory areas in a field-specific manner. These data indicate that multisensory convergence and integration are features common to all auditory cortical areas but are especially prevalent in higher areas.