Molecular signatures define subtypes of auditory afferents with distinct peripheral projection patterns and physiological properties.

Type I spiral ganglion neurons (SGNs) are the auditory afferents that transmit sound information from cochlear inner hair cells (IHCs) to the brainstem. These afferents consist of physiological subtypes that differ in their spontaneous firing rate (SR), activation threshold, and dynamic range and have been described as low, medium, and high SR fibers. Lately, single-cell RNA sequencing experiments have revealed three molecularly defined type I SGN subtypes. The extent to which physiological type I SGN subtypes correspond to molecularly defined subtypes is unclear. To address this question, we have generated mouse lines expressing CreERT2 in SGN subtypes that allow for a physiological assessment of molecular subtypes. We show that Lypd1-CreERT2 expressing SGNs represent a well-defined group of neurons that preferentially innervate the IHC modiolar side and exhibit a narrow range of low SRs. In contrast, Calb2-CreERT2 expressing SGNs preferentially innervate the IHC pillar side and exhibit a wider range of SRs, thus suggesting that a strict stratification of all SGNs into three molecular subclasses is not obvious, at least not with the CreERT2 tools used here. Genetically marked neuronal subtypes refine their innervation specificity onto IHCs postnatally during the time when activity is required to refine their molecular phenotype. Type I SGNs thus consist of genetically defined subtypes with distinct physiological properties and innervation patterns. The molecular subtype-specific lines characterized here will provide important tools for investigating the role of the physiologically distinct type I SGNs in encoding sound signals.

Association between childhood psychiatric disorders and psychotic experiences in adolescence: A population-based longitudinal study.

BACKGROUND: Adolescent psychotic experiences (PEs) are common, and are associated with both psychotic and non-psychotic illnesses. In order to examine psychopathological and cognitive antecedents of adolescent PEs, we have conducted a longitudinal study of common childhood psychiatric disorders and subsequent adolescent PEs in the population-based prospective ALSPAC birth cohort. METHOD: Depression, anxiety, attention deficit hyperactivity disorder, oppositional defiant or conduct disorder, and pervasive developmental disorder were diagnosed according to DSM-IV criteria in 8253 participants at age 8years. IQ was assessed by WISC-III also at 8years. PEs, depressive and anxiety symptoms were assessed at 13years. Logistic regression calculated odds ratio (OR) for PEs at 13years associated with psychiatric disorders at 8years. Linear regression calculated mean difference in IQ between groups with and without psychiatric disorder. Mediating effects of IQ, mood and anxiety symptoms on the psychiatric disorder-PEs relationship were examined. RESULTS: In total, 599 children were assessed to have a DSM-IV psychiatric disorder at 8years (7.2%). These children compared with those without any psychiatric disorder performed worse on all measures of IQ; adjusted mean difference in total IQ -6.17 (95% CI, -7.86, -4.48). Childhood psychiatric disorders were associated with PEs subsequently in adolescence; adjusted OR 1.96 (95% CI, 1.47-2.68). The association between psychiatric disorder and subsequent PEs was partly mediated by, independently, IQ deficit at 8years and depressive and anxiety symptoms at 13years. CONCLUSIONS: The findings indicate that adolescent PEs are associated with general cognitive ability and past and present psychopathological factors.

Subtype maturation of spiral ganglion neurons.

PURPOSE OF REVIEW: We review recent progress in the characterization of spiral ganglion neurons (SGNs), the afferent neurons that transmit sound information from mechanosensory hair cells in the inner ear to the central nervous system. RECENT FINDINGS: Single-cell ribonucleic acid sequencing studies of murine SGNs have demonstrated that SGNs consist of molecularly distinct subtypes. The molecularly defined SGN subtypes likely correspond to SGN subtypes previously identified on the basis of physiological properties, although this has not been experimentally demonstrated. Subtype maturation is completed postnatally in an activity-dependent manner and is impaired in several models of hearing loss. SUMMARY: The recent molecular studies open new avenues to rigorously test whether SGN subtypes are important for the encoding of different sound features and if they show differential vulnerability to genetic factors and environmental insults. This could have important implications for the development of therapeutic strategies to treat hearing loss.