Chronic behavioral manipulation via orally delivered chemogenetic actuator in macaques

The chemogenetic technology referred to as designer receptors exclusively activated by designer drugs (DREADDs) offers reversible means to control neuronal activity for investigating its functional correlation with behavioral action. Deschloroclozapine (DCZ), a recently-developed highly potent and selective DREADDs actuator, displays a capacity to expand the utility of DREADDs for chronic manipulation without side-effects in nonhuman primates, which has not yet been validated. Here we investigated the pharmacokinetics and behavioral effects of orally administered DCZ in macaque monkeys. Pharmacokinetic analysis and positron emission tomography (PET) occupancy examination demonstrated that oral administration of DCZ yielded slower and prolonged kinetics, and that its bioavailability was 10-20% of that in the case of systemic injection. Oral DCZ (300-1000 μg/kg) induced significant working memory impairments for at least 4 h in monkeys with hM4Di expressed in the prefrontal cortex. Repeated daily oral doses of DCZ consistently caused similar impairments over two weeks without discernible desensitization. Our results indicate that orally delivered DCZ affords a less invasive strategy for chronic but reversible chemogenetic manipulation of neuronal activity in nonhuman primates, and this has potential for clinical application.

Online Self-Regulated Learning and Achievement in the Era of Change

As education is remodelled to online solutions, instructors and students are required to adapt their teaching and learning through different forms of monitoring, regulation and assessment. This remodelling requires conceptual and philosophical reflection relating to stakeholder roles and the relationship between learners and teaching materials within digital learning spaces. With a sample of 276 student participants, this article reports from a Japanese university which shifted all regular face-to-face lectures online at short notice during 2020. Self-regulated learning is drawn from to test a primary thesis that online self-regulated learning impacts achievement. It was hypothesized that metacognitive skills provide the foundation for online self-regulated learning but are not able to exert a direct effect on achievement as such skills must be mediated through applied behavioral action. Three criterion models indicated limited achievement effect sizes between 11.1% and 12.6%. The outcomes are discussed in relation to online learning and pedagogies relevant to distance education in the era of change.