Composite receptive fields in the mouse auditory cortex

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 behavior. It has previously been shown that central auditory neurons in the starling have composite receptive fields composed of multiple features when probed with conspecific songs. Whether this property is an idiosyncratic characteristic of songbirds, a group of highly specialized vocal learners, or a generic characteristic of central auditory systems in different animals is, however, 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 auditory cortical neurons in the mouse 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 analyze mouse USVs and birdsongs. We have found that the receptive-field features obtained with the mouse USVs and those obtained with the pitch-shifted starling songs clustered together, as did the sparse-filtering features. However, the natural and artificial receptive-field features clustered mostly separately. These results indicate that composite receptive fields are likely a generic property of central auditory systems in different classes of animals. They further suggest that the quadratic receptive-field features of the mouse auditory cortical neurons are natural-stimulus invariant.

Expression and Localization of Kv1.1 and Kv3.1b Potassium Channels in the Cochlear Nucleus and Inferior Colliculus after Long-Term Auditory Deafferentation

Deafness affects the expression and distribution of voltage-dependent potassium channels (Kvs) of central auditory neurons in the short-term, i.e., hours to days, but the consequences in the expression of Kvs after long-term deafness remain unknown. We tested expression and distribution of Kv1.1 and Kv3.1b, key for auditory processing, in the rat cochlear nucleus (CN), and in the inferior colliculus (IC), at 1, 15 and 90 days after mechanical lesion of the cochlea, using a combination of qRT-PCR and Western blot in the whole CN, along with semi-quantitative immunocytochemistry in the AVCN, where the role of both Kvs in the control of excitability for accurate auditory timing signal processing is well established. Neither Kv1.1/Kv3.1b mRNA or protein expression changed significantly in the CN between 1 and 15 days after deafness. At 90 days post-lesion, however, mRNA and protein expression for both Kvs increased, suggesting that regulation of Kv1.1 and Kv3.1b expression is part of cellular mechanisms for long-term adaptation to auditory deprivation in the CN. Consistent with these findings, immunocytochemistry showed increased labeling intensity for both Kvs in the AVCN at day 90 after cochlear lesion. This increase argues that up-regulation of Kv1.1 and Kv3.1b in AVCN neurons may be required to adapt intrinsic excitability to altered input over the long term after auditory deprivation. Contrary to these findings in the CN, expression levels of Kv1.1 and Kv3.1b in the IC did not undergo major changes after cochlear lesion. In particular, there was no evidence of long-term up-regulation of either Kv1.1 or Kv3.1b, supporting that such post-lesion adaptive mechanism may not be needed in the IC. These results reveal that post-lesion adaptations do not necessarily involve stereotyped plastic mechanisms along the entire auditory pathway.

Broad binaural fusion impairs segregation of speech based on voice pitch differences in a ‘cocktail party’ environment

ABSTRACTIn the normal auditory system, central auditory neurons are sharply tuned to the same frequency ranges for each ear. This precise tuning is mirrored behaviorally as the binaural fusion of tones evoking similar pitches across ears. In contrast, hearing-impaired listeners exhibit abnormally broad tuning of binaural pitch fusion, fusing sounds with pitches differing by up to 3-4 octaves across ears into a single object. Here we present evidence that such broad fusion may similarly impair the segregation and recognition of speech based on voice pitch differences in a ‘cocktail party’ environment. Speech recognition performance in a multi-talker environment was measured in four groups of adult subjects: normal-hearing (NH) listeners and hearing-impaired listeners with bilateral hearing aids (HAs), bimodal cochlear implant (CI) worn with a contralateral HA, or bilateral CIs. Performance was measured as the threshold target-to-masker ratio needed to understand a target talker in the presence of masker talkers either co-located or symmetrically spatially separated from the target. Binaural pitch fusion was also measured. Voice pitch differences between target and masker talkers improved speech recognition performance for the NH, bilateral HA, and bimodal CI groups, but not the bilateral CI group. Spatial separation only improved performance for the NH group, indicating an inability of the hearing-impaired groups to benefit from spatial release from masking. A moderate to strong negative correlation was observed between the benefit from voice pitch differences and the breadth of binaural pitch fusion in all groups except the bilateral CI group in the co-located spatial condition. Hence, tuning of binaural pitch fusion predicts the ability to segregate voices based on pitch when acoustic cues are available. The findings suggest that obligatory binaural fusion, with a concomitant loss of information from individual streams, may occur at a level of processing before auditory object formation and segregation.

Efferent Innervation to the Cochlea

The auditory system consists of ascending and descending neuronal pathways. The best studied is the ascending pathway, whereby sounds that are transduced in the cochlea into electrical signals are sent to the brain via the auditory nerve. Before reaching the auditory cortex, auditory ascending information has several central relays: the cochlear nucleus and superior olivary complex in the brainstem, the lateral lemniscal nuclei and inferior colliculus in the midbrain, and the medial geniculate body in the thalamus. The function(s) of the descending corticofugal pathway is less well understood. It plays important roles in shaping or even creating the response properties of central auditory neurons and in the plasticity of the auditory system, such as reorganizing cochleotopic and computational maps. Corticofugal projections are present at different relays of the auditory system. This review focuses on the physiology and plasticity of the medial efferent olivocochlear system.

Gαi Proteins are Indispensable for Hearing

Background/Aims: From invertebrates to mammals, Gαi proteins act together with their common binding partner Gpsm2 to govern cell polarization and planar organization in virtually any polarized cell. Recently, we demonstrated that Gαi3-deficiency in pre-hearing murine cochleae pointed to a role of Gαi3 for asymmetric migration of the kinocilium as well as the orientation and shape of the stereociliary (“hair”) bundle, a requirement for the progression of mature hearing. We found that the lack of Gαi3 impairs stereociliary elongation and hair bundle shape in high-frequency cochlear regions, linked to elevated hearing thresholds for high-frequency sound. How these morphological defects translate into hearing phenotypes is not clear. Methods: Here, we studied global and conditional Gnai3 and Gnai2 mouse mutants deficient for either one or both Gαi proteins. Comparative analyses of global versus Foxg1-driven conditional mutants that mainly delete in the inner ear and telencephalon in combination with functional tests were applied to dissect essential and redundant functions of different Gαi isoforms and to assign specific defects to outer or inner hair cells, the auditory nerve, satellite cells or central auditory neurons. Results: Here we report that lack of Gαi3 but not of the ubiquitously expressed Gαi2 elevates hearing threshold, accompanied by impaired hair bundle elongation and shape in high-frequency cochlear regions. During the crucial reprogramming of the immature inner hair cell (IHC) synapse into a functional sensory synapse of the mature IHC deficiency for Gαi2 or Gαi3 had no impact. In contrast, double-deficiency for Gαi2 and Gαi3 isoforms results in abnormalities along the entire tonotopic axis including profound deafness associated with stereocilia defects. In these mice, postnatal IHC synapse maturation is also impaired. In addition, the analysis of conditional versus global Gαi3-deficient mice revealed that the amplitude of ABR wave IV was disproportionally elevated in comparison to ABR wave I indicating that Gαi3 is selectively involved in generation of neural gain during auditory processing. Conclusion: We propose a so far unrecognized complexity of isoform-specific and overlapping Gαi protein functions particular during final differentiation processes.