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

2018 Predoctoral Fellowships

Cold Spring Harbor Laboratory
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.

Status:

Active

Investigator:

Rupert, Deborah

Mentor:

Shea, Stephen

Grant Term:

2 years

Award Type:

Predoctoral Fellowships

Grant Amount:

$80,000.00

Website:

http://www.cshl.edu

Grant ID:

11100