GABAA receptors mediate rapid responses to the neurotransmitter GABA and are robust regulators of the brain and spinal cord neural networks that control locomotor behaviors, such as walking and swimming. In developing zebrafish, gross pharmacological blockade of these receptors causes hyperactive swimming, which is also a feature of many zebrafish epilepsy models. Although GABAA receptors are important to control locomotor behavior, the large number of subunits and homeostatic compensatory mechanisms have challenged efforts to determine subunit-selective roles. To address this issue, we mutated each of the eight zebrafish GABAA α subunit genes individually and in pairs using a CRISPR-Cas9 somatic inactivation approach, then we examined the swimming behavior of the mutants at two developmental stages, 48 and 96 hours post fertilization (hpf). We found that disrupting the expression of specific pairs of subunits resulted in different abnormalities in swimming behavior at 48 hpf. Mutation of α4 and α5 selectively resulted in longer duration swimming episodes, mutations in α3 and α4 selectively caused excess, large-amplitude body flexions (C-bends), and mutation of α3 and α5 resulted in increases in both of these measures of hyperactivity. At 96 hpf, hyperactive phenotypes were nearly absent, suggesting that homeostatic compensation was able to overcome the disruption of even multiple subunits. Taken together, our results identify subunit-selective roles for GABAA α3, α4, and α5 in regulating locomotion. Given that these subunits exhibit spatially restricted expression patterns, these results provide a foundation to identify neurons and GABAergic networks that control discrete aspects of locomotor behavior.

Introduction: Heart-healthy diets are important in preventing hypertension (HTN) and hypertensive disorders of pregnancy (HDP), leading causes of preventable maternal mortality. However, perspectives of pregnant people with these conditions on barriers and facilitators of healthy eating are not well established. This study explored these experiences through qualitative feedback. Hypothesis: There are pregnancy-specific barriers and facilitators impacting healthy eating in people with HTN or at risk for HDP. Methods: Pregnant people with HTN or at risk for HDP were recruited from a large academic medical center for an electronic survey assessing barriers and facilitators to healthy eating. Participants answered open-ended questions about barriers to healthy diets and agents for change. Qualitative responses were analyzed using thematic analysis. Results: Of 46 participants (mean age 31.6 (SD 5.5) years, 35.1% Hispanic), 71.7% (33) responded to the question about barriers to healthy eating, with 56.5% (26) reporting specific barriers and 15.2% (7) reporting no barriers. Major themes for barriers included: (1) lack of education on what is “healthy;” (2) intrinsic factors (i.e., motivation, portion control, food cravings, and food aversions); (3) lack of access due to social determinants (i.e., time, finance, housing, culture and social factors); and (4) current health problems. Furthermore, 67.4% described facilitators to support healthy eating ( Table ), with themes of (1) external support, (2) discipline/routine; (3) increased affordability; and (4) menu/grocery guidance. Conclusion: Given lack of access and food preferences were common barriers to healthy eating, pregnant people with HTN or those at risk for HDP may benefit from food insecurity screening and individualized guidance from healthcare professionals. With personalized meal plans, specific recipes, and ingredient lists attainable in terms of cost, time, and social/cultural factors, these patients may be better supported for healthy eating.

GABAA receptors mediate rapid responses to the neurotransmitter GABA and are robust regulators of the brain and spinal cord neural networks that control locomotor behaviors, such as walking and swimming. In developing zebrafish, gross pharmacological blockade of these receptors causes hyperactive swimming, which has been embraced as an epilepsy model. Although GABAA receptors are important to control locomotor behavior, the large number of subunits and homeostatic compensatory mechanisms have challenged efforts to determine subunit-selective roles. To address this issue, we mutated each of the eight zebrafish GABAA α subunit genes individually and in pairs using a CRISPR-Cas9 somatic inactivation approach, then we examined the swimming behavior of the mutants at two developmental stages. We found that disrupting the expression of specific pairs of subunits resulted in different abnormalities in swimming behavior at the first development stage. Mutation of α4 and α5 selectively resulted in longer duration swimming episodes, mutations in α3 and α4 selectively caused excess, large-amplitude body flexions (C-bends), and mutation of α3 and α5 resulted in increases in both of these measures of hyperactivity. At the later stage of development, hyperactive phenotypes were nearly absent, suggesting that homeostatic compensation was able to overcome the disruption of even multiple subunits. Taken together, our results identify subunit-selective roles for GABAA α3, α4, and α5 in regulating locomotion. Given that these subunits exhibit spatially restricted expression patterns, these results provide a foundation to identify neurons and GABAergic networks that control discrete aspects of locomotor behavior.