Maintaining behaviorally relevant information in spatial working memory (SWM) requires functional synchrony between the dorsal hippocampus and medial prefrontal cortex (mPFC). However, the mechanism that regulates synchrony between these structures remains unknown. Here, we used a unique dual-task approach to compare hippocampal–prefrontal synchrony while rats switched between an SWM-dependent task and an SWM-independent task within a single behavioral session. We show that task-specific representations in mPFC neuronal populations are accompanied by SWM-specific oscillatory synchrony and directionality between the dorsal hippocampus and mPFC. We then demonstrate that transient inactivation of the reuniens and rhomboid (Re/Rh) nuclei of the ventral midline thalamus abolished only the SWM-specific activity patterns that were seen during dual-task sessions within the hippocampal–prefrontal circuit. These findings demonstrate that Re/Rh facilitate bidirectional communication between the dorsal hippocampus and mPFC during SWM, providing evidence for a causal role of Re/Rh in regulating hippocampal–prefrontal synchrony and SWM-directed behavior. SIGNIFICANCE STATEMENT Hippocampal–prefrontal synchrony has long been thought to be critical for spatial working memory (SWM) and the ventral midline thalamic reuniens and rhomboid nuclei (Re/Rh) have long been considered a potential site for synchronizing the hippocampus and medial prefrontal cortex. However, the hypothesis that Re/Rh are critical for hippocampal–prefrontal synchrony and SWM has not been tested. We first used a dual-task approach to identify SWM-specific patterns of hippocampal–prefrontal synchrony. We then demonstrated that Re/Rh inactivation concurrently disrupted SWM-specific behavior and the SWM-specific patterns of hippocampal–prefrontal synchrony seen during dual-task performance. These results provide the first direct evidence that Re/Rh contribute to SWM by modulating hippocampal–prefrontal synchrony.

Working memory depends on communication between the hippocampus and the prefrontal cortex (PFC); however, the neural circuitry that mediates interactions between these brain areas has not been well characterized. Two candidate structures are the thalamic reuniens (RE) and rhomboid (Rh) nuclei, which are reciprocally connected with both the hippocampus and PFC. These known anatomical connections suggest that RE/Rh may be involved in mediating hippocampal-prefrontal communication, and therefore may be critical for working memory processing. To test the hypothesis that RE/Rh are necessary for working memory, we trained separate groups of rats to perform 1 of 2 tasks in a T-maze. The first task was a working memory-dependent conditional discrimination (CDWM) task, and the second task was a nonworking memory-dependent conditional discrimination (CD) task. These tasks took place in the same maze, featured the same number of trials, and utilized the same cue (a tactile-visual maze insert). After rats had learned either task, RE/Rh were transiently inactivated with the GABAA receptor agonist muscimol, and performance was assessed. RE/Rh inactivation caused performance deficits on the CDWM task, but not the CD task. This result suggests that RE/Rh are a necessary component of working memory task performance, which is also thought to depend on the hippocampal-prefrontal circuit. RE/Rh inactivation did not cause a performance deficit on the CD task, suggesting that RE/Rh have dissociable contributions to working memory-dependent and nonworking memory-dependent tasks, independently of the known contributions of these 2 thalamic nuclei to the sensorimotor and attention-related aspects of other memory tasks.

Surveillance data have highlighted continued disparities in neural tube defects (NTDs) by race-ethnicity in the United States. Starting in 2016, the Food and Drug Administration (FDA) authorized voluntary folic acid fortification of corn masa flour to reduce the risk of neural tube defects (NTDs) among infants of Hispanic women of reproductive age. To assess the impact of voluntary corn masa fortification, cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2011–2018 for Hispanic women of reproductive age with available red blood cell (RBC) folate concentrations were analyzed, with additional analyses conducted among Hispanic women whose sole source of folic acid intake was fortified foods (enriched cereal grain products (ECGP) only), excluding ready-to-eat cereals and supplements. RBC folate concentration (adjusted geometric mean) among Hispanic women of reproductive age did not differ between 2011–2016 and 2017–2018, though RBC folate concentration increased significantly among lesser acculturated Hispanic women consuming ECGP only. Concentrations of RBC folate for those born outside the U.S and residing in the U.S <15 years increased from 894 nmol/L (95% CI: 844–946) in 2011–2016 to 1018 nmol/L (95% CI: 982–1162; p < 0.001) in 2017–2018. Primarily Spanish-speaking Hispanic women of reproductive age who only consumed ECGP saw an increase from 941 nmol/L (95% CI: 895–990) in 2011–2016 to 1034 nmol/L (95% CI: 966–1107; p = 0.03) in 2017–2018. By subpopulation, we observed no significant changes in the proportion at risk of NTDs (<748 nmol/L) and no changes in the model-based estimated NTD rates following voluntary corn masa fortification. This analysis suggests that there is a remaining risk among Hispanics for folate sensitive NTDs, though continued monitoring of folate status in future NHANES data cycles will help inform the long-term efficacy of voluntary fortification of corn masa flour.

Impairments in social interaction in Autism Spectrum Disorder (ASD) differ greatly across individuals and vary throughout an individual's lifetime. Yet, an important marker of ASD in infancy is deviations in social-visual engagement, such as the reliably detectable early deviations in attention to the eyes or to biological movement (Klin et al., 2015). Given the critical nature of these early developmental periods, understanding its neurobehavioral underpinnings by means of a nonhuman primate model will be instrumental to understanding the pathophysiology of ASD. Like humans, rhesus macaques 1) develop in rich and complex social behaviors, 2) progressively develop social skills throughout infancy, and 3) have high similarities with humans in brain anatomy and cognitive functions (Machado and Bachevalier, 2003). In this study, male infant rhesus macaques living with their mothers in complex social groups were eye-tracked longitudinally from birth to 6 months while viewing full-faced videos of unfamiliar rhesus monkeys differing in age and sex. The results indicated a critical period for the refinement of social skills around 4-8 weeks of age in rhesus macaques. Specifically, infant monkeys' fixation to the eyes shows an inflection in developmental trajectory, increasing from birth to 8 weeks, decreasing slowly to a trough between 14-18 weeks, before increasing again. These results parallel the developmental trajectory of social visual engagement published in human infants (Jones & Klin, 2013) and suggest the presence of a switch in the critical networks supporting these early developing social skills that is highly conserved between rhesus macaque and human infant development.

Background: Current studies examining the effects of high concentrations of red blood cell (RBC) or serum folates assume that high folate concentrations are an indicator of high folic acid intakes, often ignoring the contributions of other homeostatic and biological processes, such as kidney function. Objective: The current study examined the relative contributions of declining kidney function, as measured by the risk of chronic kidney disease (CKD), and usual total folic acid intake on the concentrations of RBC folate and serum folate (total as well as individual folate forms). Design: Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) collected in 2-year cycles were combined from 2011 to 2018. A total of 18,127 participants aged ≥16 years with available folate measures, kidney biomarker data (operationalized as a categorical CKD risk variable describing the risk of progression), and reliable dietary recall data were analyzed. Results: RBC folate concentrations increased as CKD risk increased: low risk, 1089 (95% CI: 1069, 1110) nmol/L; moderate risk, 1189 (95% CI: 1158, 1220) nmol/L; high risk, 1488 (95% CI: 1419, 1561) nmol/L; and highest risk, 1443 (95% CI: 1302, 1598) nmol/L (p < 0.0001). Similarly, serum total folate concentrations increased as CKD risk increased: low risk: 37.1 (95% CI: 26.3, 38.0) nmol/L; moderate risk: 40.2 (95% CI: 38.8, 41.7) nmol/L; high risk: 48.0 (95% CI: 44.3, 52.1) nmol/L; the highest Risk: 42.8 (95% CI: 37.8, 48.4) nmol/L (p < 0.0001). The modeled usual intake of folic acid showed no difference among CKD risk groups, with a population median of 225 (interquartile range: 108–390) µg/day. Conclusion: Both RBC and serum folate concentrations increased with declining kidney function without increased folic acid intake. When analyzing associations between folate concentrations and disease outcomes, researchers may want to consider the confounding role of kidney function.