Pharmacology of Temporal Cognition in Two Mouse Strains

Abstract

Behavioral and pharmacological testing in mice has been revamped following the development of new tools for the manipulation of genetic information. We present the results from the peak procedure, an operant test that assesses the capacity to perceive, remember, and act upon temporal information. We studied the basic timing abilities in two different strains of mice, the C57Bl/6J and C3H/HeJ, and their response to psychoactive substances. Scopolamine and high doses of d-amphetamine disrupted performance by increasing response variability. The effect of d-amphetamine was particularly clear in C3H mice. Whereas scopolamine did not seem to affect the location of the response, the effect of a low dose of d-amphetamine, a leftward shift, was consistent with the hypothesis that it accelerates the internal time keeping mechanism. Physostigmine alone improved performance by reducing variability between trials without affecting the response location. Pretreatment with physostigmine partially blocked the deleterious effects of scopolamine. Methylphenidate did not have major effects on timing behavior in C57 but in the highest dose shifted the response of C3H mice to the left. The higher sensitivity of the C3H strain to the effects of d-amphetamine and methylphenidate support its value as an animal model of attention deficit disorder. The performance of mice in this temporal task was comparable to that observed in rats and pigeons, and seemed exquisitely sensitive to pharmacological manipulation. *Mauricio R. Papini was the action editor for this paper.We are thankful to Gustavo Stolovitzky for the development of the software used for the start-stop analysis, to John Wearden for generously sharing unpublished data, to Warren Meck, Aya Sasaki and two anonymous reviewers for useful comments on an earlier version of this manuscript.

M2 receptors are required for spatiotemporal sequence learning in mouse primary visual cortex

“…Cholinergic signaling through mAChRs is implicated in multiple forms of temporal processing in humans and animal models, including spatiotemporal sequence learning, interval-timing (Abner et al, 2001; Balci et al, 2008; Zhang et al, 2019), temporal gap detection and ordinal tasks (Caine et al, 1981; Ison & Bowen, 2000), and auditory discrimination (Seki et al, 2001). Most of these works designed their experiments around scopolamine, which is a non-selective mAChR antagonist.…”