RESUMEN
Early postnatal development of corticolimbic circuitry is shaped by the environment and is vulnerable to early life challenges. Prior work has shown that early life adversity (ELA) leads to hyperinnervation of glutamatergic basolateral amygdala (BLA) projections to the prefrontal cortex (PFC) in adolescence. While hyperinnervation is associated with later-life anxiety behaviors, the physiological changes underpinning corticolimbic and behavioral impacts of ELA are not understood. We tested whether postsynaptic BLA-driven PFC activity is enhanced in ELA-exposed animals, using the maternal separation (MS) model of ELA. PFC local-field potential following BLA stimulation was facilitated in MS-exposed adolescents. Since ELA increases activity of the early-developing BLA, while the PFC exhibits protracted development, we further examined impacts of glutamatergic BLA activity during early adolescence on later-life PFC innervation and heightened anxiety. In early adolescence, MS-exposed animals exhibited decreased anxiety-like behavior, and acute adolescent BLA inhibition induced behaviors that resembled those of MS animals. To examine long-lasting impacts of adolescent BLA activity on innervation, BLA-originating axonal boutons in the PFC were quantified in late adolescence after early adolescent BLA inhibition. We further tested whether late adolescent BLA-PFC changes were associated with anxious reactivity expressed as heightened acoustic startle responses. MS rearing increased BLA-PFC innervation and threat reactivity in late adolescence, however early adolescent BLA inhibition was insufficient to prevent MS effects, suggesting that earlier BLA activity or post-synaptic receptor rearrangement in the PFC drives altered innervation. Taken together, these findings highlight both pre- and postsynaptic changes in the adolescent BLA-PFC circuit following ELA.
RESUMEN
BACKGROUND: Zambia is among the countries making major progress in limiting cases of the neglected tropical disease lymphatic filariasis on the path to reaching global elimination targets. For this trend to continue, it is essential for strategies and policies targeting the disease in Zambia to be based on the most recent and relevant literature. The scope of research on lymphatic filariasis in the Zambian context is currently poorly understood. Therefore, this study describes a scoping review protocol which will be used to analyze the body of literature on lymphatic filariasis in Zambia. METHODS: The scoping review protocol was developed following the PRISMA reporting guidelines for Scoping Reviews (PRISMA-ScR) and the JBI Scoping Review Methodology Group's guidance on conducting scoping reviews. In consultation with a research librarian, these guidelines will be applied to a literature search of articles from peer-reviewed journals, or government and international regulatory bodies using PubMed, Embase, Web of Science, Cochrane CENTRAL, WHO ICTRP, Pan African Clinical Trials Registry, and ClinicalTrials.gov. Each record will be screened at the abstract and full-text level by two independent reviewers, and results reported via summary statistics. DISCUSSION: Understanding the current state of research on lymphatic filariasis in Zambia will identify major knowledge and intervention gaps in this context, and serve as a source of information for surrounding countries in the region. As the disease prevalence drops, efforts for elimination will require carefully targeted strategies which can be informed from the literature identified in this protocol.