Perceptual Consequences of Early-Onset Hereditary Hearing Loss in the Belgian Waterslager Canary (Serinus Canarius)

Belgian Waterslager canaries (BWS) are bred for a distinctive low-pitched song that includes sounds that are thought to resemble water. This strain of canary has been used in multiple neurobiological and behavioral studies of song learning. These birds have a permanent hereditary hearing loss associated with missing and abnormal hair cells. The hearing deficit develops after hatch, but is present when the birds learn their song. The manner in which these birds process complex sounds indisputably affects the content of their vocalizations; however, no studies have looked at BWS canaries' ability to detect and discriminate sounds other than detection of pure tones in quiet. Thus, the BWS canary provides a unique opportunity to investigate the relationship between the form and function of an auditory system involved in vocal learning. Here I describe a series of psychoacoustic experiments that investigate differences in masking, discrimination, temporal processing, and perception of song elements in BWS canaries and normal-hearing non-BWS canary strains. Spectral and temporal studies of masking showed that frequency resolution and the phase response of the basilar papilla are impaired in BWS canaries. Frequency discrimination was superb at low frequencies, but worse than normal at high frequencies in BWS canaries. Duration and intensity discrimination was not adversely affected by the hearing loss. Temporal resolution was normal or better than normal under some conditions in BWS canaries. Despite the hearing loss, BWS canaries are able to accurately discriminate among strain-specific song syllables as well as syllables of other canary strains. In fact, BWS canaries are actually better than non-BWS canaries at discriminating among BWS canary syllables. These perceptual predispositions in BWS canaries are presumably related to the structural abnormalities of the inner ear, and are likely to play a role in song learning and song maintanence by enhancing the birds' ability to attend to important acoustic features that are characteristic of BWS vocalizations

Mice Lacking the Alpha9 Subunit of the Nicotinic Acetylcholine Receptor Exhibit Deficits in Frequency Difference Limens and Sound Localization

Sound processing in the cochlea is modulated by cholinergic efferent axons arising from medial olivocochlear neurons in the brainstem. These axons contact outer hair cells in the mature cochlea and inner hair cells during development and activate nicotinic acetylcholine receptors composed of α9 and α10 subunits. The α9 subunit is necessary for mediating the effects of acetylcholine on hair cells as genetic deletion of the α9 subunit results in functional cholinergic de-efferentation of the cochlea. Cholinergic modulation of spontaneous cochlear activity before hearing onset is important for the maturation of central auditory circuits. In α9KO mice, the developmental refinement of inhibitory afferents to the lateral superior olive is disturbed, resulting in decreased tonotopic organization of this sound localization nucleus. In this study, we used behavioral tests to investigate whether the circuit anomalies in α9KO mice correlate with sound localization or sound frequency processing. Using a conditioned lick suppression task to measure sound localization, we found that three out of four α9KO mice showed impaired minimum audible angles. Using a prepulse inhibition of the acoustic startle response paradigm, we found that the ability of α9KO mice to detect sound frequency changes was impaired, whereas their ability to detect sound intensity changes was not. These results demonstrate that cholinergic, nicotinic α9 subunit mediated transmission in the developing cochlear plays an important role in the maturation of hearing

Functional, Morphological, and Evolutionary Characterization of Hearing in Subterranean, Eusocial African Mole-Rats

Naked mole-rats are highly vocal, eusocial, subterranean rodents with, counterintuitively, poor hearing. The causes underlying their altered hearing are unknown. Moreover, whether altered hearing is degenerate or adaptive to their unique lifestyles is controversial. We used various methods to identify the factors contributing to altered hearing in naked and the related Damaraland mole-rats and to examine whether these alterations result from relaxed or adaptive selection. Remarkably, we found that cochlear amplification was absent from both species despite normal prestin function in outer hair cells isolated from naked mole-rats. Instead, loss of cochlear amplification appears to result from abnormal hair bundle morphologies observed in both species. By exploiting a well-curated deafness phenotype-genotype database, we identified amino acid substitutions consistent with abnormal hair bundle morphology and reduced hearing sensitivity. Amino acid substitutions were found in unique groups of six hair bundle link proteins. Molecular evolutionary analyses revealed shifts in selection pressure at both the gene and the codon level for five of these six hair bundle link proteins. Substitutions in three of these proteins are associated exclusively with altered hearing. Altogether, our findings identify the likely mechanism of altered hearing in African mole-rats, making them the only identified mammals naturally lacking cochlear amplification. Moreover, our findings suggest that altered hearing in African mole-rats is adaptive, perhaps tailoring hearing to eusocial and subterranean lifestyles. Finally, our work reveals multiple, unique evolutionary trajectories in African mole-rat hearing and establishes species members as naturally occurring disease models to investigate human hearing loss

A statistical review of light curves and the prevalence of contact binaries in the Kuiper Belt

We investigate what can be learned about a population of distant Kuiper Belt Objects (KBOs) by studying the statistical properties of their light curves. Whereas others have successfully inferred the properties of individual, highly variable KBOs, we show that the fraction of KBOs with low amplitudes also provides fundamental information about a population. Each light curve is primarily the result of two factors: shape and orientation. We consider contact binaries and ellipsoidal shapes, with and without flattening. After developing the mathematical framework, we apply it to the existing body of KBO light curve data. Principal conclusions are as follows. (1) When using absolute magnitude H as a proxy for the sizes of KBOs, it is more accurate to use the maximum of the light curve (minimum H) rather than the mean. (2) Previous investigators have noted that smaller KBOs tend to have higher-amplitude light curves, and have interpreted this as evidence that they are systematically more irregular in shape than larger KBOs; we show that a population of flattened bodies with uniform proportions, independent of size, could also explain this result. (3) Our method of analysis indicates that prior assessments of the fraction of contact binaries in the Kuiper Belt may be artificially low. (4) The pole orientations of some KBOs can be inferred from observed changes in their light curves over time scales of decades; however, we show that these KBOs constitute a biased sample, whose pole orientations are not representative of the population overall. (5) Although surface topography, albedo patterns, limb darkening, and other surface properties can affect individual light curves, they do not have a strong influence on the statistics overall. (6) Photometry from the Outer Solar System Origins Survey (OSSOS) survey is incompatible with previous results and its statistical properties defy easy interpretation. We also discuss the promise of this approach for the analysis of future, much larger data sets such as the one anticipated from the upcoming Vera C. Rubin Observatory

A statistical review of light curves and the prevalence of contact binaries in the Kuiper Belt

We investigate what can be learned about a population of distant Kuiper Belt Objects (KBOs) by studying the statistical properties of their light curves. Whereas others have successfully inferred the properties of individual, highly variable KBOs, we show that the fraction of KBOs with low amplitudes also provides fundamental information about a population. Each light curve is primarily the result of two factors: shape and orientation. We consider contact binaries and ellipsoidal shapes, with and without flattening. After developing the mathematical framework, we apply it to the existing body of KBO light curve data. Principal conclusions are as follows. (1) When using absolute magnitude H as a proxy for the sizes of KBOs, it is more accurate to use the maximum of the light curve (minimum H) rather than the mean. (2) Previous investigators have noted that smaller KBOs tend to have higher-amplitude light curves, and have interpreted this as evidence that they are systematically more irregular in shape than larger KBOs; we show that a population of flattened bodies with uniform proportions, independent of size, could also explain this result. (3) Our method of analysis indicates that prior assessments of the fraction of contact binaries in the Kuiper Belt may be artificially low. (4) The pole orientations of some KBOs can be inferred from observed changes in their light curves over time scales of decades; however, we show that these KBOs constitute a biased sample, whose pole orientations are not representative of the population overall. (5) Although surface topography, albedo patterns, limb darkening, and other surface properties can affect individual light curves, they do not have a strong influence on the statistics overall. (6) Photometry from the Outer Solar System Origins Survey (OSSOS) survey is incompatible with previous results and its statistical properties defy easy interpretation. We also discuss the promise of this approach for the analysis of future, much larger data sets such as the one anticipated from the upcoming Vera C. Rubin Observatory

Debugging and consolidating multiple synthetic chromosomes reveals combinatorial genetic interactions

The Sc2.0 project is building a eukaryotic synthetic genome from scratch. A major milestone has been achieved with all individual Sc2.0 chromosomes assembled. Here, we describe the consolidation of multiple synthetic chromosomes using advanced endoreduplication intercrossing with tRNA expression cassettes to generate a strain with 6.5 synthetic chromosomes. The 3D chromosome organization and transcript isoform profiles were evaluated using Hi-C and long-read direct RNA sequencing. We developed CRISPR Directed Biallelic URA3-assisted Genome Scan, or ‘‘CRISPR D-BUGS,’’ to map phenotypic variants caused by specific designer modifications, known as ‘‘bugs.’’ We first fine-mapped a bug in synthetic chromosome II (synII) and then discovered a combinatorial interaction associated with synIII and synX, revealing an unexpected genetic interaction that links transcriptional regulation, inositol metabolism, and tRNASer CGA abundance. Finally, to expedite consolidation, we employed chromosome substitution to incorporate the largest chromosome (synIV), thereby consolidating &gt;50% of the Sc2.0 genome in one strain </p

Counting on the mental number line to make a move: sensorimotor ('pen') control and numerical processing

Mathematics is often conducted with a writing implement. But is there a relationship between numerical processing and sensorimotor ‘pen’ control? We asked participants to move a stylus so it crossed an unmarked line at a location specified by a symbolic number (1–9), where number colour indicated whether the line ran left–right (‘normal’) or vice versa (‘reversed’). The task could be simplified through the use of a ‘mental number line’ (MNL). Many modern societies use number lines in mathematical education and the brain’s representation of number appears to follow a culturally determined spatial organisation (so better task performance is associated with this culturally normal orientation—the MNL effect). Participants (counter-balanced) completed two consistent blocks of trials, ‘normal’ and ‘reversed’, followed by a mixed block where line direction varied randomly. Experiment 1 established that the MNL effect was robust, and showed that the cognitive load associated with reversing the MNL not only affected response selection but also the actual movement execution (indexed by duration) within the mixed trials. Experiment 2 showed that an individual’s motor abilities predicted performance in the difficult (mixed) condition but not the easier blocks. These results suggest that numerical processing is not isolated from motor capabilities—a finding with applied consequences