Frick previously demonstrated a link between BKCa channel dysfunction, neocortical hyperexcitability and sensory hypersensitivity in the Fmr1-/y model of ASD. Drawing on this work, Frick will explore the potential of channel agonists for the therapeutic correction of phenotypes associated neocortical hyperexcitability/sensory hypersensitivity in genetic mouse models of ASD.
This project aims to study pharmacological tools that enhance energy production efficiency in neurons as a way to enhance learning and memory in individuals with fragile X syndrome.
Yu will leverage genomic data from SPARK, SSC and other large ASD cohorts to catalog biallelic/recessive ASD mutations, analyze phenotypic correlates and provide novel mechanistic insights.
Choi proposes to use the MIA mouse model with a discrete, functionally relevant lesion in the primary somatosensory cortex to elucidate neural circuits that modulate ASD-associated behaviors.
Gu will assess the contribution of mtDNA mutations to ASD by examining whole-genome sequencing SSC data and using maternal and fetal samples collected in the Boston Birth Cohort.
Lukens and Zunder will utilize transcriptomics, mass cytometry and data-driven science to uncover cellular and molecular underpinnings of sex bias in an MIA model of autism.
This project proposes to perform single-nucleus RNA sequencing analysis of postmortem brain samples from children and adolescents with autism. The results will provide insight into region- and cell-type‐specific molecular changes in autism at an unprecedented level of resolution and should help to explain variations in disease phenotypes.
Macklis will directly investigate growth cone molecular machinery of cerebral cortex inter-hemispheric, associative, callosal projection neurons (CPN); abnormalities of CPN connectivity; and dose-dependent direct effects of aberrant cortical associative circuitry on social interaction behavior in mice mutant for the ASD risk gene Bcl11a/Ctip1.
Sulzer will examine whether loss of the normal developmental maturation of striatal neuron excitability in ASD mouse models underlies striatal deficits.
Mourrain aims to identify common synaptic defects shared by different mouse genetic ASD models and to evaluate the efficacy of existing drugs on these synaptic changes.