Interval Timing is altered in male Nrxn1+/- mice: Just as in Autism Spectrum Disorder

Autism spectrum disorder (ASD) is characterised by impaired social interaction and communication and increased repetitive and stereotypical behaviour. Neuroimaging shows functional abnormalities in brain areas involved in temporal processing of ASD, and individuals with ASD show deficits in interval timing. Neurexin (Nrxn) genes have been identified in a wide variety of neuropsychiatric disorders, including ASD, and Nrxn1+/- mice possess a mutation that disrupts the α, β, and ɣ isoforms of Nrxn1, a gene that is involved in the structure of synapses. We investigated the interval timing abilities of the Nrxn1+/- mouse model of ASD in the peak interval procedure with a 15s target interval. Two-month-old male Nrxn1+/- and C57BL/6J littermate control mice were trained to obtain sucrose liquid rewards 15s after the onset of a discriminative stimulus (discrete fixed-interval training) and their timing responses were tested in probe trials that lasted much longer and reinforcement was omitted. We found that the Nrxn1+/- mice responded earlier than the control mice on the probe trials, resulting in a leftward shift in their average response curve (i.e., shorter peak time). No differences were found in measures of temporal differentiation, number of responses, or response amplitude. These findings are consistent with a prior study of timing behaviour in individuals with ASD as well as leftward shifts observed with a different (experimental) mouse model of ASD. In conclusion, we believe that these results are indicative of a biassed long-term memory in the Nrxn1+/- mouse model of ASD, and add to the growing knowledge of timing behaviour in ASD.

This work will be submitted once the paper characterizing the Nrxn1 mouse model is published.