In utero exposure to valproic acid disrupts ascending projections to the central nucleus of the inferior colliculus from the auditory brainstem.

Prenatal exposure to the antiepileptic valproic acid (VPA) is associated with an increased risk of autism spectrum disorder (ASD) in humans. Accordingly, in utero exposure to VPA is a validated and biologically relevant animal model of ASD. The majority of individuals with ASD exhibit some degree of auditory dysfunction, ranging from deafness to hypersensitivity. Animals exposed to VPA in utero have abnormal tonotopic maps and responses in the cerebral cortex and hyperactivation, hypoplasia, abnormal neuronal morphology and reduced calcium binding protein expression throughout the auditory brainstem nuclei. Further, our previous work suggests that GABAergic neuronal populations may be more severely impacted by in utero VPA exposure. However, the axonal projection patterns of brainstem nuclei to the inferior colliculus (IC) have not been investigated in VPA-exposed animals. Herein, we use stereotaxic injections of the retrograde tracer Fast Blue into the central nucleus of the IC (CNIC) and examine the proportions of retrogradely labeled neurons in the nuclei of the lateral lemniscus, superior olivary complex and cochlear nuclei. Our results indicate that not only are there fewer neurons in the auditory brainstem after VPA exposure, but also that fewer neurons are retrogradely labeled from the CNIC. Together, our results indicate that in utero VPA exposure may result in altered patterns of input to the auditory midbrain.

Exposures to fine particulate matter (PM2.5) and ozone above USA standards are associated with auditory brainstem dysmorphology and abnormal auditory brainstem evoked potentials in healthy young dogs.

BACKGROUND: Delayed central conduction times in the auditory brainstem have been observed in Mexico City (MC) healthy children exposed to fine particulate matter (PM2.5) and ozone (O3) above the current United States Environmental Protection Agency (US-EPA) standards. MC children have α synuclein brainstem accumulation and medial superior olivary complex (MSO) dysmorphology. The present study used a dog model to investigate the potential effects of air pollution on the function and morphology of the auditory brainstem. METHODOLOGY: Twenty-four dogs living in clean air v MC, average age 37.1 ± 26.3 months, underwent brainstem auditory evoked potential (BAEP) measurements. Eight dogs (4 MC, 4 Controls) were analysed for auditory brainstem morphology and histopathology. RESULTS: MC dogs showed ventral cochlear nuclei hypotrophy and MSO dysmorphology with a significant decrease in cell body size, decreased neuronal packing density with regions in the nucleus devoid of neurons and marked gliosis. MC dogs showed significant delayed BAEP absolute wave I, III and V latencies compared to controls. CONCLUSIONS: MC dogs show auditory nuclei dysmorphology and BAEPs consistent with an alteration of the generator sites of the auditory brainstem response waveform. This study puts forward the usefulness of BAEPs to study auditory brainstem neurodegenerative changes associated with air pollution in dogs. Recognition of the role of non-invasive BAEPs in urban dogs is warranted to elucidate novel neurodegenerative pathways link to air pollution and a promising early diagnostic strategy for Alzheimer's Disease.

Characterization of the superior olivary complex of Canis lupus domesticus.

The superior olivary complex (SOC) is a collection of brainstem auditory nuclei which play essential roles in the localization of sound sources, temporal coding of vocalizations and descending modulation of the cochlea. Notwithstanding, the SOC nuclei vary considerably between species in accordance with the auditory needs of the animal. The canine SOC was subjected to anatomical and physiological examination nearly 50 years ago and was then virtually forgotten. Herein, we aimed to characterize the nuclei of the canine SOC using quantitative morphometrics, estimation of neuronal number, histochemistry for perineuronal nets and immunofluorescence for the calcium binding proteins calbindin and calretinin. We found the principal nuclei to be extremely well developed: the lateral superior olive (LSO) contained over 20,000 neurons and the medial superior olive (MSO) contained over 15,000 neurons. In nearly all non-chiropterian terrestrial mammals, the MSO exists as a thin, vertical column of neurons. The canine MSO was folded into a U-shaped contour and had associated with the ventromedial tip a small, round collection of neurons we termed the tail nucleus of the MSO. Further, we found evidence within the LSO, MSO and medial nucleus of the trapezoid body (MNTB) for significant morphological variations along the mediolateral or rostrocaudal axes. Finally, the majority of MNTB neurons were calbindin-immunopositive and associated with calretinin-immunopositive calyceal terminals. Together, these observations suggest the canine SOC complies with the basic plan of the mammalian SOC but possesses a number of unique anatomical features.