Mice with mutations in Trpm1, a gene in the locus of 15q13.3 microdeletion syndrome, display pronounced hyperactivity and decreased anxiety-like behavior.

The 15q13.3 microdeletion syndrome is a genetic disorder characterized by a wide spectrum of psychiatric disorders that is caused by the deletion of a region containing 7 genes on chromosome 15 (MTMR10, FAN1, TRPM1, MIR211, KLF13, OTUD7A, and CHRNA7). The contribution of each gene in this syndrome has been studied using mutant mouse models, but no single mouse model recapitulates the whole spectrum of human 15q13.3 microdeletion syndrome. The behavior of Trpm1-/- mice has not been investigated in relation to 15q13.3 microdeletion syndrome due to the visual impairment in these mice, which may confound the results of behavioral tests involving vision. We were able to perform a comprehensive behavioral test battery using Trpm1 null mutant mice to investigate the role of Trpm1, which is thought to be expressed solely in the retina, in the central nervous system and to examine the relationship between TRPM1 and 15q13.3 microdeletion syndrome. Our data demonstrate that Trpm1-/- mice exhibit abnormal behaviors that may explain some phenotypes of 15q13.3 microdeletion syndrome, including reduced anxiety-like behavior, abnormal social interaction, attenuated fear memory, and the most prominent phenotype of Trpm1 mutant mice, hyperactivity. While the ON visual transduction pathway is impaired in Trpm1-/- mice, we did not detect compensatory high sensitivities for other sensory modalities. The pathway for visual impairment is the same between Trpm1-/- mice and mGluR6-/- mice, but hyperlocomotor activity has not been reported in mGluR6-/- mice. These data suggest that the phenotype of Trpm1-/- mice extends beyond that expected from visual impairment alone. Here, we provide the first evidence associating TRPM1 with impairment of cognitive function similar to that observed in phenotypes of 15q13.3 microdeletion syndrome.

Evaluation of critical flicker-fusion frequency measurement methods using a touchscreen-based visual temporal discrimination task in the behaving mouse.

The critical flicker-fusion frequency (CFF), defined as the frequency at which a flickering light is indistinguishable from a continuous light, is a useful measure of visual temporal resolution. The mouse CFF has been studied by electrophysiological approaches such as recordings of the electroretinogram (ERG) and the visually evoked potential (VEP), but it has not been measured behaviorally. Here we estimated the mouse CFF by using a touchscreen based operant system. The test with ascending series of frequencies and that with randomized frequencies resulted in about 17 and 14 Hz, respectively, as the frequency which could not be distinguished from steady lights. Since the ascending method of limits tend to overestimate the threshold than the descending method, we estimated the mouse CFF to be about 14 Hz. Our results highlight usefulness of the operant conditioning method in measurement of the mouse visual temporal resolution.