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The impact of MECP2 mutation in gabaergic interneurons on plasticity in the auditory cortex

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Rupert, Deborah

Shea, Stephen

Cold Spring Harbor Laboratory


2 years

Predoctoral Fellowships

Cold Spring Harbor

New York

United States



Autism Spectrum Disorders (ASD) are characterized by difficulty with social behavior and verbal communication. Rett Syndrome (RTT) is a neurodevelopmental disorder caused by loss of function mutations in the X-linked MECP2 gene, and shares many features of the communication deficits seen in patients with ASD. The monogenicity of RTT simplifies the development animal models; facilitating the study of pathophysiological mechanisms underlying RTT and, more broadly, ASD and neurodevelopmental disorders. As complete loss of MECP2 is lethal, RTT most often affects heterozygous females. The study will examine the effects of heterozygous Mecp2 mutations using a female mouse model (Mecp2 het) that exhibits impaired auditory processing. Wild type females, but not Mecp2 heterozygous animals, learn to retrieve infant pups in response to high-pitched pup distress calls (ultrasonic vocalizations). Recent work suggests that this results from impaired plasticity in the auditory cortex, a structure critical for processing vocalizations. The current goal is to determine how mutations in the Mecp2 gene alter inhibitory circuits in the auditory cortex and impair vocal perception. We will use a combination of behavioral analysis, molecular neuroanatomy imaging, and in vivo electrophysiology recordings to identify structural and functional consequences of mecp2 mutation in the brain. Moreover, we aim to identify targets for ameliorating these consequences.

Cognitive/ Behavioral Neuroscience, Electrophysiology - Cellular, Language & Communication, Social Behavior/ Social Cognition, Neuroscience, Confocal, Gene Knock-Out/ Knock-In Models, Neurophysiology, Biology, Mice

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