Interval timing is crucial for decision-making and motor control and is impaired in many neuropsychiatric disorders, including schizophrenia — a neurodevelopmental disorder with a strong genetic component. Several gene mutations, polymorphisms or rare copy number variants have been associated with schizophrenia. L1 cell adhesion molecules (L1CAMs) are involved in neurodevelopmental processes, and in synaptic function and plasticity in the adult brain. Mice deficient in the Close Homolog to L1 (CHL1) adhesion molecule show alterations of hippocampal and thalamo-cortical neuroanatomy as well as deficits in sensorimotor gating and exploratory behavior. We analyzed interval timing and attentional control of temporal and spatial information in male CHL1 deficient (KO) mice and wild type (WT) controls. In a 20-s peak-interval timing procedure (standard and reversed), KO mice showed a maintained leftward shift of the response function relative to WT, indicative of a deficit in memory encoding/decoding. In trials with 2, 5, or 10-s gaps, KO mice shifted their peak times less than WT controls at longer gap durations, suggesting a decreased (attentional) effect of interruptions. In the spatial–temporal task, KO mice made more working and reference memory errors than controls, suggestive of impaired use of spatial and/or temporal information. When the duration spent on the central platform of the maze was manipulated, WT mice showed fewer spatial errors at the trained duration than at shorter or longer durations, indicative of discrimination based upon spatial–temporal integration. In contrast, performance was similar at all tested durations in KO mice, indicative of control by spatial cues, but not by temporal cues. These results suggest that CHL1 KO mice selectively attend to the more relevant cues of the task, and fail to integrate more complex spatial–temporal information, possibly as a result of reduced memory capacity related to hippocampal impairment, and altered temporal-integration mechanisms possibly due to thalamo-cortical anomalies.
Interval Timing by Long-Range Temporal Integration
