Edward Chang aims to address auditory and speech processing in individuals with epilepsy and autism, with the specific goal of understanding how auditory, phonological and linguistic representations are affected. Understanding how these well-characterized neural representations of speech-relevant acoustic features are impacted in individuals with autism at the level of specific populations of neurons will provide mechanistic insight that may lead to behavioral, pharmacological and neuromodulatory therapies that act in much more targeted ways than is currently possible.

Seizures are an extreme outcome of excitatory-inhibitory imbalance and are the most common neurological complication in autism spectrum disorder (ASD). Seizures are even more common in syndromic forms of ASD such as Angelman syndrome. In the current project, Ben Philpot’s laboratory aims to identify the circuitry and protein pathways underlying seizures in a mouse model of Angelman syndrome, with the goal of identifying disease-modifying targets to treat seizures. The mechanistic insights yielded by these studies may further guide therapeutically oriented investigations of excitatory-inhibitory imbalance across the broader spectrum of ASDs.

In the current project, Andreas Frick and Stefan Heinemann plan to investigate if big-conductance calcium- and voltage-activated potassium (BK_Ca) channel agonists could be a potential therapeutic treatment of atypical sensory experience in autism. These studies will be performed using a variety of in vitro and in vivo experimental systems, including human stem-cell derived neuronal models of autism and genetic mouse models of autism.

The sensory and neural mechanisms that mediate social communication facilitating attachment and how they are affected in the context of autism spectrum disorder (ASD) are poorly understood. Prairie voles are small rodents that display long-term relationships between peers and mates. Devanand Manoli proposes to understand how specific mutations in two ASD risk genes, Shank3 and Scn2a, disrupt the processing of social cues, leading to the identification of brain regions that could inform targeted interventions to improve social communication in ASD.