Representation Of Sound Frequency Research Articles

A stable sensory map emerges from a dynamic equilibrium of neurons with unstable tuning properties.

Recent long-term measurements of neuronal activity have revealed that, despite stability in large-scale topographic maps, the tuning properties of individual cortical neurons can undergo substantial reformatting over days. To shed light on this apparent contradiction, we captured the sound response dynamics of auditory cortical neurons using repeated 2-photon calcium imaging in awake mice. We measured sound-evoked responses to a set of pure tone and complex sound stimuli in more than 20,000 auditory cortex neurons over several days. We found that a substantial fraction of neurons dropped in and out of the population response. We modeled these dynamics as a simple discrete-time Markov chain, capturing the continuous changes in responsiveness observed during stable behavioral and environmental conditions. Although only a minority of neurons were driven by the sound stimuli at a given time point, the model predicts that most cells would at least transiently become responsive within 100days. We observe that, despite single-neuron volatility, the population-level representation of sound frequency was stably maintained, demonstrating the dynamic equilibrium underlying the tonotopic map. Our results show that sensory maps are maintained by shifting subpopulations of neurons "sharing" the job of creating a sensory representation.

Spike-Timing Dependent Plasticity of Inhibition Gates Critical Period Remodeling in Auditory Cortex

In auditory cortex, sensory experience during a critical developmental period leads to remodeling of sound frequency representation. Parvalbumin-expressing interneurons (PV-INs) mediate feedforward inhibition in thalamocortical circuits; a disinhibition at the output synapses of PV-INs might be a prerequisite for critical period plasticity. Here, we find a marked spike-timing dependent plasticity at the synapses between PVINs and principal neurons in the input layer of auditory cortex. Long-term potentiation of inhibition (iLTP) is observed upon postsynaptic (principal neuron) then presynaptic (PV-IN) AP firing. The opposite AP sequence causes GABAB mediated long-term depression of inhibition (iLTD), which, upon further development, is converted to iLTP in an experiencedependent manner. Genetic deletion of GABAB receptors in principal neurons converts iLTD to iLTP, and causes profound deficits in critical period plasticity. Thus, in the auditory cortex of young mice, GABAB signaling in principal neurons enforces iLTD at PV-IN output synapses, thereby gating critical period plasticity.

Sound Frequency Representation in the Auditory Cortex of the Common Marmoset Visualized Using Optical Intrinsic Signal Imaging.

Natural sound is composed of various frequencies. Although the core region of the primate auditory cortex has functionally defined sound frequency preference maps, how the map is organized in the auditory areas of the belt and parabelt regions is not well known. In this study, we investigated the functional organizations of the core, belt, and parabelt regions encompassed by the lateral sulcus and the superior temporal sulcus in the common marmoset (Callithrix jacchus). Using optical intrinsic signal imaging, we obtained evoked responses to band-pass noise stimuli in a range of sound frequencies (0.5–16 kHz) in anesthetized adult animals and visualized the preferred sound frequency map on the cortical surface. We characterized the functionally defined organization using histologically defined brain areas in the same animals. We found tonotopic representation of a set of sound frequencies (low to high) within the primary (A1), rostral (R), and rostrotemporal (RT) areas of the core region. In the belt region, the tonotopic representation existed only in the mediolateral (ML) area. This representation was symmetric with that found in A1 along the border between areas A1 and ML. The functional structure was not very clear in the anterolateral (AL) area. Low frequencies were mainly preferred in the rostrotemplatal (RTL) area, while high frequencies were preferred in the caudolateral (CL) area. There was a portion of the parabelt region that strongly responded to higher sound frequencies (>5.8 kHz) along the border between the rostral parabelt (RPB) and caudal parabelt (CPB) regions.

Effects of Electrical Stimulation in the Inferior Colliculus on Frequency Discrimination by Rhesus Monkeys and Implications for the Auditory Midbrain Implant.

Understanding the relationship between the auditory selectivity of neurons and their contribution to perception is critical to the design of effective auditory brain prosthetics. These prosthetics seek to mimic natural activity patterns to achieve desired perceptual outcomes. We measured the contribution of inferior colliculus (IC) sites to perception using combined recording and electrical stimulation. Monkeys performed a frequency-based discrimination task, reporting whether a probe sound was higher or lower in frequency than a reference sound. Stimulation pulses were paired with the probe sound on 50% of trials (0.5-80 μA, 100-300 Hz, n = 172 IC locations in 3 rhesus monkeys). Electrical stimulation tended to bias the animals' judgments in a fashion that was coarsely but significantly correlated with the best frequency of the stimulation site compared with the reference frequency used in the task. Although there was considerable variability in the effects of stimulation (including impairments in performance and shifts in performance away from the direction predicted based on the site's response properties), the results indicate that stimulation of the IC can evoke percepts correlated with the frequency-tuning properties of the IC. Consistent with the implications of recent human studies, the main avenue for improvement for the auditory midbrain implant suggested by our findings is to increase the number and spatial extent of electrodes, to increase the size of the region that can be electrically activated, and to provide a greater range of evoked percepts. Patients with hearing loss stemming from causes that interrupt the auditory pathway after the cochlea need a brain prosthetic to restore hearing. Recently, prosthetic stimulation in the human inferior colliculus (IC) was evaluated in a clinical trial. Thus far, speech understanding was limited for the subjects and this limitation is thought to be partly due to challenges in harnessing the sound frequency representation in the IC. Here, we tested the effects of IC stimulation in monkeys trained to report the sound frequencies they heard. Our results indicate that the IC can be used to introduce a range of frequency percepts and suggest that placement of a greater number of electrode contacts may improve the effectiveness of such implants.

Functional Microarchitecture of the Mouse Dorsal Inferior Colliculus Revealed through In Vivo Two-Photon Calcium Imaging.

Due to its genetic tractability, the mouse is fast becoming the most popular animal model for sensory neuroscience. Nevertheless, many aspects of its neural architecture are still poorly understood. Here, we image the dorsal auditory midbrain and its inputs from the cortex, revealing a hitherto hidden level of organization and paving the way for the direct observation of corticocollicular interactions. We show that a precise functional organization exists in the mouse auditory midbrain, which has been missed by previous, more macroscopic approaches. The fine-scale distribution of sound-frequency tuning suggests that the mouse midbrain is more similar to that of other mammals than previously thought and contrasts with the more heterogeneous organization reported in imaging studies of auditory cortex.

Intercollicular commissural connections refine the representation of sound frequency and level in the auditory midbrain.

Connections unifying hemispheric sensory representations of vision and touch occur in cortex, but for hearing, commissural connections earlier in the pathway may be important. The brainstem auditory pathways course bilaterally to the inferior colliculi (ICs). Each IC represents one side of auditory space but they are interconnected by a commissure. By deactivating one IC in guinea pig with cooling or microdialysis of procaine, and recording neural activity to sound in the other, we found that commissural input influences fundamental aspects of auditory processing. The areas of nonV frequency response areas (FRAs) were modulated, but the areas of almost all V-shaped FRAs were not. The supra-threshold sensitivity of rate level functions decreased during deactivation and the ability to signal changes in sound level was decremented. This commissural enhancement suggests the ICs should be viewed as a single entity in which the representation of sound in each is governed by the other.

Greenwood frequency–position relationship in the primary auditory cortex in guinea pigs

Although orderly representation of sound frequency over space is a hallmark feature of the primary auditory cortex (A1), the quantitative relationship between sound frequency and cortical position is unclear. We examined this relationship in the guinea pig A1 by presenting a series of stimulus tones with a wide frequency range, and recording the evoked cortical responses using an optical imaging technique with high spatial resolution. We identified the cortical positions of three best-frequency indices for each tone: the onset response position, the peak amplitude position, and the maximum rise rate position of the response. We found a nonlinear log frequency–position relationship for each of the three indices, and the frequency–position relationship was always well described by a Greenwood equation, with correlation coefficients greater than 0.98. The cortical magnification factor, measured in octave/mm, was found to be a function of frequency, i.e. not a constant. Our results are novel in that they demonstrate a quantitative relationship between sound frequency and cortical position in the guinea pig A1, as described by the Greenwood equation.

The impact of preceding noise on the frequency tuning of rat auditory cortex neurons

BackgroundIn a natural environment, contextual noise frequently occurs with a signal sound for detection or discrimination in a temporal relation. However, the representation of sound frequency by auditory cortical neurons in a noisy environment is not fully understood. Therefore, the purpose of this study was to explore the impact of contextual noise on the cortical tuning to signal sound frequency in order to better understand the mechanism of cortical frequency coding in a complex acoustical environment.ResultsWe compared the excitatory frequency-level receptive fields (FLRFs) of neurons in the rat primary auditory cortex determined under both quiet and preceding noise conditions. Based on the changes of minimum threshold and the extent of FLRF of auditory cortical neurons, we found that the FLRFs of a cortical neuron were modulated dynamically by a varying preceding noise. When the interstimulus interval between noise and the probe tone was constant, the modulation of the FLRF increased as the level of noise was increased. If the preceding noise level was constant, the modulation decreased when the interstimulus interval was increased. Preceding noise sharpened the bandwidth of the FLRFs of 47.6% tested neurons. Moreover, preceding noise shifted the CFs of 47.6% neurons by more than 0.25 octaves, while the CFs of the rest of the neurons remained relatively unchanged.ConclusionsThe results indicate that the cortical representation of sound frequency is dynamically modulated by contextual acoustical environment, and that there are cortical neurons whose characteristic frequencies were resistant to the interference of contextual noise.

Sound frequency representation in primary auditory cortex is level tolerant for moderately loud, complex sounds

The distribution of neuronal characteristic frequencies over the area of primary auditory cortex (AI) roughly reflects the tonotopic organization of the cochlea. However, because the area of AI activated by any given sound frequency increases erratically with sound level, it has generally been proposed that frequency is represented in AI not with a rate-place code but with some more complex, distributed code. Here, on the basis of both spike and local field potential (LFP) recordings in the anesthetized cat, we show that the tonotopic representation in AI is much more level tolerant when mapped with spectrotemporally dense tone pip ensembles rather than with individually presented tone pips. That is, we show that the tuning properties of individual unit and LFP responses are less variable with sound level under dense compared with sparse stimulation, and that the spatial frequency resolution achieved by the AI neural population at moderate stimulus levels (65 dB SPL) is better with densely than with sparsely presented sounds. This implies that nonlinear processing in the central auditory system can compensate (in part) for the level-dependent coding of sound frequency in the cochlea, and suggests that there may be a functional role for the cortical tonotopic map in the representation of complex sounds.

A map of periodicity orthogonal to frequency representation in the cat auditory cortex.

Harmonic sounds, such as voiced speech sounds and many animal communication signals, are characterized by a pitch related to the periodicity of their envelopes. While frequency information is extracted by mechanical filtering of the cochlea, periodicity information is analyzed by temporal filter mechanisms in the brainstem. In the mammalian auditory midbrain envelope periodicity is represented in maps orthogonal to the representation of sound frequency. However, how periodicity is represented across the cortical surface of primary auditory cortex (AI) remains controversial. Using optical recording of intrinsic signals, we here demonstrate that a periodicity map exists in primary AI of the cat. While pure tone stimulation confirmed the well-known frequency gradient along the rostro-caudal axis of AI, stimulation with harmonic sounds revealed segregated bands of activation, indicating spatially localized preferences to specific periodicities along a dorso-ventral axis, nearly orthogonal to the tonotopic gradient. Analysis of the response locations revealed an average gradient of − 100° ± 10° for the periodotopic, and −12° ± 18° for the tonotopic map resulting in a mean angle difference of 88°. The gradients were 0.65 ± 0.08 mm/octave for periodotopy and 1.07 ± 0.16 mm/octave for tonotopy indicating that more cortical territory is devoted to the representation of an octave along the tonotopic than along the periodotopic gradient. Our results suggest that the fundamental importance of pitch, as evident in human perception, is also reflected in the layout of cortical maps and that the orthogonal spatial organization of frequency and periodicity might be a more general cortical organization principle.

Manipulating critical period closure across different sectors of the primary auditory cortex

During early brain development and through 'adult' experience-dependent plasticity, neural circuits are shaped to represent the external world with high fidelity. When raised in a quiet environment, the rat primary auditory cortex (A1) has a well-defined 'critical period', lasting several days, for its representation of sound frequency. The addition of environmental noise extends the critical period duration as a variable function of noise level. It remains unclear whether critical period closure should be regarded as a unified, externally gated event that applies for all of A1 or if it is controlled by progressive, local, activity-driven changes in this cortical area. We found that rearing rats in the presence of a spectrally limited noise band resulted in the closure of the critical period for A1 sectors representing the noise-free spectral bands, whereas the critical period appeared to remain open in noise-exposed sectors, where the cortex was still functionally and physically immature.

Non-plastic reorganization of frequency coding in the inferior colliculus of the rat following noise-induced hearing loss

It is well established that restricted mechanical lesions of the cochlea result in reorganization of the tonotopic map in the auditory thalamus and cortex, but it is unclear whether acoustic trauma produces similar effects at earlier stages of the auditory pathways. To test whether the tonotopic map is reorganized after acoustic trauma at the midbrain level, i.e. the inferior colliculus (IC), we exposed rats to an acoustic trauma and let them survive for at least 5 weeks to ensure that we produced a permanent threshold shift. Experiments were carried out in urethane-anesthetized animals 35–296 days after the traumatic exposure. The acoustic lesions were assessed by measuring the compound action potential. We mapped the frequency organization of the IC using multiunit recordings. In addition, we recorded frequency response areas (FRAs) when a single unit was isolated (N=142). The results show that acoustic trauma produces a persistent reorganization of the tonotopic map and that the normal stepwise representation of sound frequency in the IC is profoundly disrupted. Although the reorganization in the IC is similar to that previously described in the cortex and thalamus in that the affected area appears to be invaded by the adjacent normal frequencies, changes in thresholds and FRAs in these regions are different from those in the forebrain. We conclude that most of the changes can be explained by the residual-response hypothesis [Irvine DR, Rajan R, Smith S (2003) Effects of restricted cochlear lesions in adult cats on the frequency organization of the inferior colliculus. J Comp Neurol 467:354–374]. Plastic reorganization of frequency response areas and tonotopic organization does not seem to occur at the midbrain level following acoustic trauma in adult animals in a manner similar to that previously shown in the auditory cortex. Maintaining the stability of the neuronal circuitry for frequency coding in the IC may be important for the treatment of noise-induced hearing loss.

A sharper view from the top

Maintaining a precise representation of sound frequency in auditory cortex is difficult because of converging diffuse thalamocortical inputs. A recent study demonstrates that this is accomplished via recurrent intracortical connections.

Sound frequency representation in cat auditory cortex

Using the intrinsic signal optical recording technique, we reconstructed the two-dimensional pattern of stimulus-evoked neuronal activities in the auditory cortex of anesthetized and paralyzed cats. The average magnitude of intrinsic signal in response to a pure tone stimulus increased steadily as the sound pressure level increased. A detailed analysis demonstrated that the evoked signals at early frames were scaled by the sound pressure level, which in turn indicated the presence of a minimum level of sound pressure beyond which stimulus-related intrinsic signal can be generated. Intrinsic signals evoked significantly by pure tone stimuli of different frequencies were localized and arranged in an orderly manner in the middle ectosylvian gyrus, which indicates that the primary auditory field (AI) is tonotopically organized. The arrangement of optimal frequencies obtained from optical recordings of the same auditory cortex, which were conducted on different days, was highly reproducible. Furthermore, other auditory fields surrounding AI in the recorded area were allocated based on the observed tonotopicity. We also conducted unit recordings on the cats used for optical recording with the same set of acoustic stimuli. The gross feature of the arrangement of optimal frequencies determined by unit recordings agreed with the tonotopic arrangement determined by the optical recording, although the precise agreement was not obtained.

Auditory system: A neural substrate for frequency selectivity?

Recent results have provided new insights into the complexity of sound frequency representation in the auditory midbrain and may identify a neural substrate for behaviourally determined frequency resolution.

Binaural organization of primary auditory cortex in the ferret (Mustela putorius)

1. The distribution of binaural responses within the ferret's primary auditory cortex was determined by standard microelectrode mapping techniques. Single and multiple unit responses were recorded from the middle ectosylvian gyrus of barbiturate-anesthetized animals with tungsten microelectrodes (1.2-1.8 M omega) inserted into the brain perpendicular to the cortical surface. The characteristic frequency (CF) and binaural response characteristics were determined for each point sampled. 2. Gated pure tones were delivered independently to the two ears through a sealed sound system, and binaural response types were determined by comparison of evoked activity for monaural and binaural stimulation. Most binaural responses fell into one of three major groups: binaural summation (EE/F), binaural suppression (EO/I), or mixed binaural summation and suppression. 3. The neurons tended to be grouped together on the basis of their binaural response properties. Zones of binaural summation and suppression extended across the surface of the middle ectosylvian gyrus and intersected with regions of sound frequency representation. 4. Particular attention was paid to the distribution of binaural responses within isofrequency contours in the ferret's primary auditory cortex (AI). Along the length of each isofrequency contour, areas of EE/F alternated with areas of EO/I. The summation areas were typically between 0.5 and 0.7 mm wide. Single neurons with mixed binaural response properties were frequently found between groups of EE/F and EO/I cells. The mixed responses appeared to mark a transition in location between zones of summation and suppression responses. 5. The distribution of interaural intensity difference (IID) thresholds was also examined along the length of isofrequency contours. No systematic relation was found between IID threshold and the distance along an isofrequency contour.

Frequency organization of the dorsal cochlear nucleus in cats.

Sensory epithelia are often spatially reiterated throughout their representation in the central nervous system. Differential expression of this representation can reveal specializations of the organism's behavioral repertoire. For example, the nature of the central representation of sound frequency in the auditory system has provided important clues in understanding ecological pressures for acoustic processing. In this context, we used electrophysiological techniques to map the frequency organization of the dorsal cochlear nucleus in nine cats. Frequency responses were sampled in increments of 100-200 microns along electrode tracks that entered the dorsomedial border of the nucleus and exited at the ventrolateral border. Electrode tracks were oriented parallel to the long (or strial) axis of the nucleus so that each penetration sampled neural responses for most of the cat's audible frequencies and remained in or near the pyramidal cell layer for several millimeters. Nearly identical distance versus frequency relationships were obtained for different rostral-caudal locations within the same cat as well as for different cats. Frequency responses systematically decreased from above 50 kHz at the most dorsomedial locations in the nucleus to below 1 kHz in the most ventrolateral regions. The rate of frequency change was roughly three times greater in high frequency regions than in low frequency regions. In addition, the highest pyramidal cell density and longest rostral-caudal axis was observed for the middle third of the dorsal-ventral axis of the nucleus. As a result, roughly half of all pyramidal cells responded to frequencies between 8-30 kHz. The representation of neural tissue for these frequencies may be related to the importance of spectral cues in sound locations.

Frequency representation in the auditory midbrain and forebrain of a marsupial, the northern native cat (Dasyurus hallucatus).

The representation of sound frequency was examined in the auditory cortex and inferior colliculus of anaesthetized marsupial native cats (Dasyurus hallucatus) using microelectrode mapping techniques. The tonotopic organizations of these two auditory regions are grossly similar to those described in brush-tailed possums and in Eutheria. There appears to exist a biased representation of high frequencies (greater than 10kHz) in native cats and a paucity of frequencies below 1 kHz. Unit threshold audiograms indicate minimum thresholds between 7 and 12kHz and high thresholds above 30kHz.

Abnormal tonotopic organization in the ventral cochlear nucleus of the hearing-impaired DBA/2 mouse

The representation of sound frequency by auditory neurons (tonotopic organization) was evaluated in the ventral cochlear nucleus (VCN) of DBA/2 mice, a strain with impaired sensitivity to the highest and lowest frequencies heard by normal mice. Tuning curves were obtained from multiple-unit activity (MUA) and compared with those of C57 mice, which do not have severe hearing loss. Tuning curves in the C57 VCN displayed the dorsoventral progression from high- to low-frequency sensitivity that is typical of mammals. By contrast, tuning curves of DBA mice varied little as a function of dorsoventral location, and most MUA thresholds were lowest for frequencies within a narrow range (about 12–16 kHz). Thus, normal tonotopic organization is absent in the DBA mouse's VCN. In addition, because of the consistently low thresholds for 12–16 kHz tones in DBA MUA, mean thresholds for these frequencies are lower than those of C57 MUA in the dorsal and ventral portions of the VCN.

Tonotopic organization of rabbit auditory cortex

The representation of sound frequency within the auditory cortex of New Zealand and Dutch Belted rabbits was investigated using tangential microelectrode penetrations. Both multiunit and evoked potential responses to tone bursts were examined. The auditory cortex of the rabbit was found to lie caudal to the genu of the rhinal sulcus on the lateral surface of the temporal cortex. Two contiguous and tonotopically organized fields were found: a large primary field and a smaller secondary field dorsal and anterior to it. Within the primary field there is a complete and orderly representation of sound frequency. The highest best frequencies (ca. 30.5 kHz) are represented in the dorsal part of the field; the lowest best frequencies (ca 0.4 kHz) are represented in the ventral part of the field. The frequency range of 1 to 18 kHz was represented in greatest detail. The primary field was coextensive with cortex exhibiting cytoarchitectonic features characteristic of sensory cortex: a wide, cell-dense lamina III/IV, a broad, sparsely cellular lamina V, and a well-developed lamina VI. The secondary field also contains an orderly tonotopic organization but it is reverse to that of the primary field. Its highest best frequencies were located ventrally and its lowest best frequencies dorsally. The auditory region in the rabbit is compared with that of two previously mapped, smooth-brain mammals—the squirrel and the guinea pig.