No abstract

Temporal processing in the seconds-to-minutes range, known as interval timing, is a crucial cognitive function that requires activation of cortico-striatal circuits via dopaminergic-glutamatergic pathways. In humans, both children and adults with autism spectrum disorders (ASD) present alterations in their estimation of time intervals. At present, there are no records of interval timing studies in animal models of ASD. Hence, the objective of the present work was to evaluate interval timing in a mouse model of prenatal exposure to valproic acid (VPA) - a treatment used to induce human-like autistic features in rodent models. Animals were assessed for their ability to acquire timing responses in 15-s and 45-s peak-interval (PI) procedures. Our results indicate that both female and male mice prenatally exposed to VPA present decreased timing accuracy and precision compared to control groups, as well as deviations from the scalar property. Moreover, the observed timing deficits in male VPA mice were reversed after early social enrichment. Furthermore, catecholamine determination by HPLC-ED indicated significant differences in striatal dopaminergic, but not serotonergic, content in female and male VPA mice, consistent with previously identified alterations in dopamine metabolism in ASD. These deficits in temporal processing in a mouse model of autism complement previous results in humans, and provide a useful tool for further behavioral and pharmacological studies.

Temporal processing in the brain is fundamental to environmental adaptation in humans and other animals. Biological timing ranges from the microsecond scale (e.g. sound localisation) to seasonal frequencies (such as reproductive cycles). Two of the main scales of biological timing ubiquitous in most organisms are interval timing (seconds‐to‐minutes range) and circadian timing (24 h range). Interval timing is crucial to learning, memory, decision‐making and other cognitive tasks, whereas circadian timing is essential for the regulation of several physiological and behavioural functions. Several brain areas, circuits and neuromodulators that are critical to temporal processing have now been identified. However, with the exception of the circadian system, the genetic and molecular machinery that regulates biological clocks has not been systematically examined. As a consequence, the molecular basis of these two temporal mechanisms is currently the subject of intense research, as well as their possible relationship. Key Concepts Biological timing (from microseconds to seasonal cycles) is fundamental for survival and optimal goal reaching in humans and other animals. Circadian timing (24 h) and interval timing (hundreds of milliseconds to minutes) are ubiquitous in nature and are required for normal physiology and behaviour. Dopamine metabolism in the striatum is critical for interval timing, and it is also the subject of circadian control. Circadian and interval timing may share some common pathways, including dopamine metabolism. Circadian and interval timing are seriously disrupted in human pathologies with dopamine dysfunction.