Circuit asymmetries underlie functional lateralization in the mouse auditory cortex.
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ABSTRACT:
SUBMITTER: Levy RB
PROVIDER: S-EPMC6592910 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Coordinated functioning of the two cortical hemispheres is crucial for perception. The human auditory cortex (ACx) shows functional lateralization with the left hemisphere specialized for processing speech, whereas the right analyzes spectral content. In mice, virgin females demonstrate a left-hemisphere response bias to pup vocalizations that strengthens with motherhood. However, how this lateralized function is established is unclear. We developed a widefield imaging microscope to simultaneously image both hemispheres of mice to bilaterally monitor functional responses. We found that global ACx topography is symmetrical and stereotyped. In both male and virgin female mice, the secondary auditory cortex (A2) in the left hemisphere shows larger responses than right to high-frequency tones and adult vocalizations; however, only virgin female mice show a left-hemisphere bias in A2 in response to adult pain calls. These results indicate hemispheric bias with both sex-independent and -dependent aspects. Analyzing cross-hemispheric functional correlations showed that asymmetries exist in the strength of correlations between DM-AAF and A2-AAF, while other ACx areas showed smaller differences. We found that A2 showed lower cross-hemisphere correlation than other cortical areas, consistent with the lateralized functional activation of A2. Cross-hemispheric activity correlations are lower in deaf, otoferlin knockout (OTOF-/-) mice, indicating that the development of functional cross-hemispheric connections is experience dependent. Together, our results reveal that ACx is topographically symmetric at the macroscopic scale but that higher-order A2 shows sex-dependent and independent lateralized responses due to asymmetric intercortical functional connections. Moreover, our results suggest that sensory experience is required to establish functional cross-hemispheric connectivity.
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Project description:The sensory areas of the cerebral cortex possess multiple topographic representations of sensory dimensions. The gradient of frequency selectivity (tonotopy) is the dominant organizational feature in the primary auditory cortex, whereas other feature-based organizations are less well established. We probed the topographic organization of the mouse auditory cortex at the single-cell level using in vivo two-photon Ca(2+) imaging. Tonotopy was present on a large scale but was fractured on a fine scale. Intensity tuning, which is important in level-invariant representation, was observed in individual cells, but was not topographically organized. The presence or near absence of putative subthreshold responses revealed a dichotomy in topographic organization. Inclusion of subthreshold responses revealed a topographic clustering of neurons with similar response properties, whereas such clustering was absent in supra-threshold responses. This dichotomy indicates that groups of nearby neurons with locally shared inputs can perform independent parallel computations in the auditory cortex.
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Project description:BACKGROUND: Individuals with the rare genetic disorder Williams-Beuren syndrome (WS) are known for their characteristic auditory phenotype including strong affinity to music and sounds. In this work we attempted to pinpoint a neural substrate for the characteristic musicality in WS individuals by studying the structure-function relationship of their auditory cortex. Since WS subjects had only minor musical training due to psychomotor constraints we hypothesized that any changes compared to the control group would reflect the contribution of genetic factors to auditory processing and musicality. METHODOLOGY/PRINCIPAL FINDINGS: Using psychoacoustics, magnetoencephalography and magnetic resonance imaging, we show that WS individuals exhibit extreme and almost exclusive holistic sound perception, which stands in marked contrast to the even distribution of this trait in the general population. Functionally, this was reflected by increased amplitudes of left auditory evoked fields. On the structural level, volume of the left auditory cortex was 2.2-fold increased in WS subjects as compared to control subjects. Equivalent volumes of the auditory cortex have been previously reported for professional musicians. CONCLUSIONS/SIGNIFICANCE: There has been an ongoing debate in the neuroscience community as to whether increased gray matter of the auditory cortex in musicians is attributable to the amount of training or innate disposition. In this study musical education of WS subjects was negligible and control subjects were carefully matched for this parameter. Therefore our results not only unravel the neural substrate for this particular auditory phenotype, but in addition propose WS as a unique genetic model for training-independent auditory system properties.
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Project description:It has been proposed that sound information is separately streamed into onset and offset pathways for parallel processing. However, how offset responses contribute to auditory perception remains unclear. Here, loose-patch and whole-cell recordings in awake mouse primary auditory cortex (A1) reveal that a subset of pyramidal neurons exhibit a transient "Off" response, with its onset tightly time-locked to the sound termination and its frequency tuning similar to that of the transient "On" response. Both responses are characterized by excitation briefly followed by inhibition, with the latter mediated by parvalbumin (PV) inhibitory neurons. Optogenetically manipulating sound-evoked A1 responses at different temporal phases or artificially creating phantom sounds in A1 further reveals that the A1 phasic On and Off responses are critical for perceptual discrimination of sound duration. Our results suggest that perception of sound duration is dependent on precisely encoding its onset and offset timings by phasic On and Off responses.
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Project description:Purposedetermine if language disorder in children with autistic disorder (AD) corresponds to abnormalities in hemispheric asymmetries in auditory language cortex.MethodsMRI morphometric study in children with AD (n = 50) to assess hemispheric asymmetries in auditory language cortex. A key region of interest was the planum temporale (PT), which is larger in the left hemisphere in most healthy individuals.Results(i) Heschl's gyrus and planum polare showed typical hemisphere asymmetry patterns; (ii) posterior Superior Temporal Gyrus (pSTG) showed significant rightward asymmetry; and (iii) PT showed a trend for rightward asymmetry that was significant when constrained to right-handed boys (n = 30). For right-handed boys, symmetry indices for pSTG were significantly positively correlated with those for PT. PT asymmetry was age dependent, with greater rightward asymmetry with age.Conclusionsresults provide evidence for rightward asymmetry in auditory association areas (pSTG and PT) known to subserve language processing. Cumulatively, our data provide evidence for a differing maturational path for PT for lower functioning children with AD, with both pre- and post-natal experience likely playing a role in PT asymmetry.Electronic supplementary materialThe online version of this article (doi:10.1007/s11689-009-9010-2) contains supplementary material, which is available to authorized users.
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Project description:Hemispheric specialization is a fundamental feature of human brain organization. However, it is not yet clear to what extent the lateralization of specific cognitive processes may be evident throughout the broad functional architecture of cortex. While the majority of people exhibit left-hemispheric language dominance, a substantial minority of the population shows reverse lateralization. Using twin and family data from the Human Connectome Project, we provide evidence that atypical language dominance is associated with global shifts in cortical organization. Individuals with atypical language organization exhibit corresponding hemispheric differences in the macroscale functional gradients that situate discrete large-scale networks along a continuous spectrum, extending from unimodal through association territories. Analyses reveal that both language lateralization and gradient asymmetries are, in part, driven by genetic factors. These findings pave the way for a deeper understanding of the origins and relationships linking population-level variability in hemispheric specialization and global properties of cortical organization.
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Project description:The primary auditory cortex (A1) plays a key role for sound perception since it represents one of the first cortical processing stations for sounds. Recent studies have shown that on the cellular level the frequency organization of A1 is more heterogeneous than previously appreciated. However, many of these studies were performed in mice on the C57BL/6 background which develop high frequency hearing loss with age making them a less optimal choice for auditory research. In contrast, mice on the CBA background retain better hearing sensitivity in old age. Since potential strain differences could exist in A1 organization between strains, we performed comparative analysis of neuronal populations in A1 of adult (~ 10 weeks) C57BL/6 mice and F1 (CBAxC57) mice. We used in vivo 2-photon imaging of pyramidal neurons in cortical layers L4 and L2/3 of awake mouse primary auditory cortex (A1) to characterize the populations of neurons that were active to tonal stimuli. Pure tones recruited neurons of widely ranging frequency preference in both layers and strains with neurons in F1 (CBAxC57) mice exhibiting a wider range of frequency preference particularly to higher frequencies. Frequency selectivity was slightly higher in C57BL/6 mice while neurons in F1 (CBAxC57) mice showed a greater sound-level sensitivity. The spatial heterogeneity of frequency preference was present in both strains with F1 (CBAxC57) mice exhibiting higher tuning diversity across all measured length scales. Our results demonstrate that the tone evoked responses and frequency representation in A1 of adult C57BL/6 and F1 (CBAxC57) mice are largely similar.
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Project description:A central question in sensory neuroscience is how neurons represent complex natural stimuli. This process involves multiple steps of feature extraction to obtain a condensed, categorical representation useful for classification and behaviour. It has previously been shown that central auditory neurons in the starling have composite receptive fields composed of multiple features. Whether this property is an idiosyncratic characteristic of songbirds, a group of highly specialized vocal learners or a generic property of sensory processing is unknown. To address this question, we have recorded responses from auditory cortical neurons in mice, and characterized their receptive fields using mouse ultrasonic vocalizations (USVs) as a natural and ethologically relevant stimulus and pitch-shifted starling songs as a natural but ethologically irrelevant control stimulus. We have found that these neurons display composite receptive fields with multiple excitatory and inhibitory subunits. Moreover, this was the case with either the conspecific or the heterospecific vocalizations. We then trained the sparse filtering algorithm on both classes of natural stimuli to obtain statistically optimal features, and compared the natural and artificial features using UMAP, a dimensionality-reduction algorithm previously used to analyse mouse USVs and birdsongs. We have found that the receptive-field features obtained with both types of the natural stimuli clustered together, as did the sparse-filtering features. However, the natural and artificial receptive-field features clustered mostly separately. Based on these results, our general conclusion is that composite receptive fields are not a unique characteristic of specialized vocal learners but are likely a generic property of central auditory systems. KEY POINTS: Auditory cortical neurons in the mouse have composite receptive fields with several excitatory and inhibitory features. Receptive-field features capture temporal and spectral modulations of natural stimuli. Ethological relevance of the stimulus affects the estimation of receptive-field dimensionality.
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