Data from: Cntnap2 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 suggests that alteration of striatal circuits,
which mediate motor learning, action selection, and habit formation, may
contribute to the manifestation of RRBs. CNTNAP2 is a
syndromic ASD risk gene, and loss of function
of Cntnap2 in mice is associated with RRBs. How loss
of Cntnap2 impacts striatal neuron function is largely unknown.
In this study, we utilized Cntnap2^-/-^ mice to test whether
altered striatal neuron activity contributes to aberrant motor behaviors
relevant to ASD. We assessed excitatory, inhibitory, and intrinsic
physiological function of the primary striatal cell type, SPNs, as well as
a primary striatal interneuron class, PV-INs, using whole cell patch clamp
electrophysiology in Cntnap2^+/+^ and Cntnap2^-/-^ mice. We find that
Cntnap2^-/-^ mice exhibit increased cortical drive of direct pathway
striatal projection neurons (dSPNs). This enhanced drive is likely due to
increased intrinsic excitability of dSPNs, as we find no change in
interneuron number or function. We hypothesize that this enhanced
excitability of dSPNs underlies their increased responsiveness to cortical
inputs. Behaviorally, we find that Cntnap2^-/-^ mice exhibit spontaneous
repetitive behaviors in the open field, marble burying and holeboard
assays, increased motor routine learning on the accelerating rotarod
assay, and increased perseveration and cognitive inflexibility in the
four-choice reversal learning assay. We conclude that increased
corticostriatal drive of the direct pathway may therefore contribute to
the acquisition of repetitive, inflexible behaviors in Cntnap2 mice.