In-utero Zika virus (ZIKV) infection is a significant public health threat for infants as it can be vertically transmitted from mother to fetus resulting in several health problems including physical and neurodevelopmental deficits. Current diagnostic approaches for confirming in-utero ZIKV infection rely on detection of ZIKV RNA or ZIKV-specific IgM antibodies in infants after birth. These biomolecules are inherently transient making it difficult to reliably confirm in-utero infection, especially in the case of maternal infections that happen early in gestation. ZIKV-specific IgG detection in infants after 12 months of age suggests the development of their independent production of ZIKV-specific IgG when maternal IgG has cleared and not passively transferred maternal IgG, which is suggestive of in-utero infection. Previously, we have shown that ZIKV-infection of pregnant macaques results in differential maternal infection control, like what is seen in human cases. We hypothesize that poor maternal infection control in pregnant macques will result in greater rates of fetal infection causing ZIKV-specific IgG detection in infant samples for more than 12 months. We will measure ZIKV-specific IgG titers in ZIKV-exposed infant serum samples using a whole virion ELISA at 1, 3, 6, 12, 18, 24, 30, and 36 months of age and determine association with maternal virologic control. Further investigation and research may lead to enhanced diagnostic methods that allow for earlier detection and timely interventions in infants, improving their quality of life.

The social environment around us influences our behavior. For example, divergent social behaviors emerge from different durations of social isolation (Lee et al., 2021). Acute social isolation produces prosocial behaviors, and chronic social isolation results in antisocial behaviors following re-introduction to a social group. Many lines of research point toward the medial prefrontal cortex (mPFC) as a potential region for processing and representing features in our social environment. However, the exact time course of social isolation and its impact on social behavior remains an outstanding question, and the neural circuitry underlying social homeostasis remains unknown. To explore how the mPFC encodes social information and undergoes a state change following social isolation, we used in vivo cellular resolution calcium imaging coupled with computer vision and machine learning tools to measure mPFC neural activity and behavioral responses as animals engaged in a juvenile intruder task. As part of this experimental design, adult male mice are presented with a novel juvenile male mouse in acute versus chronic isolation conditions (2hr, 6hr, 24hr, 7d, 14d, and 28d) to first determine how different durations of isolation impact social behavior. We recorded their social interaction time and performed multi-animal pose estimation using SLEAP (Pereira et al., 2022) to discover differences in behavioral motifs. Additionally, we conducted calcium imaging using miniature endoscopes in the mPFC of mice engaged in social behavior after group-housing and isolation. Overall, our findings may uncover the neural mechanisms relevant to our processing of social information to dictate our interactions with the environment.

Previous research has shown that humans with cocaine use disorder exhibit hyperactivity in the ventromedial prefrontal cortex (vmPFC). Similarly, animal studies have shown increased phosphoinositide 3-kinase (PI3K), protein kinase B (Akt1) and mammalian target of rapamycin (mTOR) signaling in the vmPFC of rats following cue-elicited cocaine-craving. Previously, our lab showed Everolimus, an FDA-approved mTOR inhibitor, dose-dependently blocks cue-elicited responding for cocaine as well as incubation-related changes in the PL (prelimbic) subregion of the vmPFC. Herein, adult male and female Sprague Dawley rats conditioned to self-administer sucrose pellets underwent gavage infusion with vehicle or Everolimus prior to cue testing. Subsequent immunoblot studies assessed mTOR activation in the PL and infralimbic (IL) subregions of the vmPFC. Lastly, male and female rats trained to lever-press for sucrose pellets received microinjections of vehicle or Everolimus into the PL. Systemic gavage infusions of Everolimus reduced phospho-mTOR levels in the IL but did not decrease sucrose-seeking compared to early withdrawal controls. Microinjections of Everolimus into the PL also did not have any effect on sucrose intake compared to vehicle treatment. Thus, both systemic and localized administration of Everolimus failed to reduce sucrose-intake and sucrose-seeking, respectively. Since incubated sucrose-craving is not associated with elevated mTOR activity in the vmPFC nor is mTOR activity necessary for incubated sucrose craving, these findings suggest distinct mechanisms and neural adaptations for cocaine vs. sucrose-seeking.