Genetic Control of a Central Pattern Generator: Rhythmic Oromotor Movement in Mice Is Controlled by a Major Locus near Atp1a2

Fluid licking in mice is a rhythmic behavior that is controlled by a central pattern generator (CPG) located in a complex of brainstem nuclei. C57BL/6J (B6) and DBA/2J (D2) strains differ significantly in water-restricted licking, with a highly heritable difference in rates (h2≥0.62) and a corresponding 20% difference in interlick interval (mean ± SEM = 116.3±1 vs 95.4±1.1 ms). We systematically quantified motor output in these strains, their F1 hybrids, and a set of 64 BXD progeny strains. The mean primary interlick interval (MPI) varied continuously among progeny strains. We detected a significant quantitative trait locus (QTL) for a CPG controlling lick rate on Chr 1 (Lick1), and a suggestive locus on Chr 10 (Lick10). Linkage was verified by testing of B6.D2-1D congenic stock in which a segment of Chr 1 of the D2 strain was introgressed onto the B6 parent. The Lick1 interval on distal Chr 1 contains several strong candidate genes. One of these is a sodium/potassium pump subunit (Atp1a2) with widespread expression in astrocytes, as well as in a restricted population of neurons. Both this subunit and the entire Na+/K+-ATPase molecule have been implicated in rhythmogenesis for respiration and locomotion. Sequence variants in or near Apt1a2 strongly modulate expression of the cognate mRNA in multiple brain regions. This gene region has recently been sequenced exhaustively and we have cataloged over 300 non-coding and synonymous mutations segregating among BXD strains, one or more of which is likely to contribute to differences in central pattern generator tempo

Estimating the robustness of questionnaire results: lessons from a mixed-mode survey of expectations for teleworking & road-based business travel

The robustness of questionnaire results to various forms of bias are explored in the context of a dual-mode (web and hardcopy) survey of employers’ anticipations of levels of employee commuting and business travel activity under a range of future ICT scenarios. The questionnaire incorporated several innovative features which, together with the dual-mode format, allowed an unusually wide range of analyses. For example: the robustness of respondents’ opinions was tested by examining the effect of incorporating alternative versions of a briefing text, one being very positive and one very negative, about the role of ICT; instrument bias was identified via detailed comparison of the results from the two versions of the questionnaire; and the impact of exogenous factors which are often ignored or taken as constant was assessed via special supplementary questions. Analysis showed that the robustness of opinions and expectations varied and was influenced by respondent characteristics, and that results from the two versions of the questionnaire differed significantly. It is concluded that opinions and expectations are less robust, and questionnaire results are more subject to bias and myopic interpretation, than is generally recognised and that web-based surveys seem particularly vulnerable to sampling bias. Methods are suggested for measuring robustness, for reducing bias and for validating and contextualising results. The use of contrasting briefing texts is recommended as a means of establishing the robustness of opinions and expectations while supplementary questions are recommended for validating and contextualising SP and SE exercises