Haploinsufficiency of in Striatal Indirect Pathway Neurons Alters Motor and Goal-Directed Behaviors in Mice.

is a high-confidence autism spectrum disorder (ASD) risk gene, and mutations in lead to a neurodevelopmental disorder (NDD) that presents with epilepsy, ASD, motor developmental delay, and intellectual disability. codes for Ras/Rap GTP-ase activating protein SynGAP (SynGAP). SynGAP is located in the postsynaptic density of glutamatergic synapses and regulates glutamate receptor trafficking in an activity-dependent manner.

loss drives striatal neuron hyperexcitability and behavioral inflexibility.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by two major diagnostic criteria - persistent deficits in social communication and interaction, and the presence of restricted, repetitive patterns of behavior (RRBs). Evidence from both human and animal model studies of ASD suggest that alteration of striatal circuits, which mediate motor learning, action selection, and habit formation, may contribute to the manifestation of RRBs. is a syndromic ASD risk gene, and loss of function of in mice is associated with RRBs.

Altered motor learning and coordination in mouse models of autism spectrum disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with increasing prevalence. Over 1,000 risk genes have now been implicated in ASD, suggesting diverse etiology. However, the diagnostic criteria for the disorder still comprise two major behavioral domains - deficits in social communication and interaction, and the presence of restricted and repetitive patterns of behavior (RRBs).

Loss of Tsc1 from striatal direct pathway neurons impairs endocannabinoid-LTD and enhances motor routine learning.

Tuberous sclerosis complex (TSC) is a neurodevelopmental disorder that often presents with psychiatric conditions, including autism spectrum disorder (ASD). ASD is characterized by restricted, repetitive, and inflexible behaviors, which may result from abnormal activity in striatal circuits that mediate motor learning and action selection. To test whether altered striatal activity contributes to aberrant motor behaviors in the context of TSC, we conditionally deleted Tsc1 from direct or indirect pathway striatal projection neurons (dSPNs or iSPNs, respectively).