Malformation of the superior olivary complex in an animal model of autism.

Autism is a neurodevelopmental disorder characterized by social difficulties, impaired communication skills and repetitive behavioral patterns. Additionally, there is evidence that auditory deficits are a common feature of the autism spectrum disorders. Despite the prevalence of autism, the neurobiology of this disorder is poorly understood. However, abnormalities in neuronal morphology, cell number and connectivity have been described throughout the autistic brain. Indeed, we have demonstrated significant dysmorphology in the superior olivary complex (SOC), a collection of auditory brainstem nuclei, in the autistic brain. Prenatal exposure to valproic acid (VPA) in humans has been associated with autism and in rodents prenatal VPA exposure produces many neuroanatomical and behavioral deficits associated with autism. Thus, in an effort to devise an animal model of the autistic auditory brainstem, we have investigated neuronal number and morphology in animals prenatally exposed to valproic acid (VPA). In VPA exposed rats, we find significantly fewer neurons and significant alterations in neuronal morphology. Thus, prenatal VPA exposure in rats appears to produce similar dysmorphology as we have reported in the autistic human brain.

Distribution of perineuronal nets in the human superior olivary complex.

Perineuronal nets (PNNs) are specialized assemblies of chondroitin sulfate proteoglycans (CSPGs) in the central nervous system that form a lattice-like covering over the cell body, primary dendrites and initial axon segment of select neuronal populations. PNNs appear to play significant roles in development of the central nervous system, neuronal protection, synaptic plasticity and local ion homeostasis. In seven human brainstems (average age=81 years), we have utilized Wisteria floribunda (WFA) histochemistry and immunocytochemistry for CSPG to map the distribution of PNNs within the nuclei of the human superior olivary complex (SOC). Within the SOC, the majority of net-bearing neurons are situated in the most medially situated nuclei, especially the superior paraolivary nucleus and medial nucleus of the trapezoid body. Net-bearing neurons are consistently found in the ventral nucleus of the trapezoid body and posterior periolivary nucleus, but to a lesser extent in the lateral nucleus of the trapezoid body. Finally, perineuronal nets are typically absent from the lateral and medial superior olives.