Development of corticothalamic circuits of prefrontal cortex in mouse models of autism

  • Awarded: 2016
  • Award Type: Pilot
  • Award #: 401358

Autism spectrum disorders (ASDs) represent a group of neurodevelopmental disorders for which the underlying etiologies are heterogeneous. Risk factors range from environmental insults to single gene mutations. A unifying model explaining how this array of risk factors leads to deficits in communication, social interactions, and sensory and repetitive behavior is lacking.

Chinfei Chen and her colleagues propose that disrupted circuit development underlies many of the core symptoms in ASD. Specifically, Chen’s team argues that disruption of circuits between the prefrontal cortex (PFC), a region important for social behavior, and the thalamus, a subcortical region important in sensory integration, causes many of the observed ASD phenotypes. In support of this hypothesis, Chen’s team recently demonstrated that abnormal cortical activity during critical periods of development can alter the connectivity of sensory inputs onto the thalamus1. Based on their findings, the group hypothesizes that focal disruptions of PFC activity, resulting from heterogeneous etiologies, can lead to progressively abnormal development of subcortical networks important in gating social, sensory and motor information.

Chen’s team plans to study the circuit between the PFC and the thalamic reticular nucleus (TRN), a thalamic nucleus that integrates information from multiple sensory, motor and limbic cortical regions. Little is known about how this circuit develops, or whether it is abnormal in mouse models of ASD. The team will first examine whether there is aberrant development of this circuit in two monogenetic models of ASDs, SHANK3 and FMR1. They will also perturb this corticothalamic circuit (using pharmacogenetic techniques) in normally developing mice to examine effects on the plasticity of this circuit and to test whether such mice exhibit ASD-related behaviors. If validated, this circuit disruption model may provide a unifying framework for approaching neurodevelopmental disorders such as ASD.



1.Thompson A.D. et al. Neuron 91, 1021-1033 (2016) PubMed
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