Lasting impact of postnatal maternal separation on the developing BNST: lifelong socioemotional consequences

Elsevier, Neuropharmacology, Volume 225, 2023
Lindsay R. Halladay, Steven M. Herron

Nearly one percent of children in the US experience childhood neglect or abuse, which can incite lifelong emotional and behavioral disorders. Many studies investigating the neural underpinnings of maleffects inflicted by early life stress have largely focused on dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Newer veins of evidence suggest that exposure to early life stressors can interrupt neural development in extrahypothalamic areas as well, including the bed nucleus of the stria terminalis (BNST). One widely used approach in this area is rodent maternal separation (MS), which typically consists of separating pups from the dam for extended periods of time, over several days during the first weeks of postnatal life – a time when pups are highly dependent on maternal care for survival. MS has been shown to incite myriad lasting effects not limited to increased anxiety-like behavior, hyper-responsiveness to stressors, and social behavior deficits. The behavioral effects of MS are widespread and thus unlikely to be limited to hypothalamic mechanisms. Recent work has highlighted the BNST as a critical arbiter of some of the consequences of MS, especially socioemotional behavioral deficits. The BNST is a well-documented modulator of anxiety, reward, and social behavior by way of its connections with hypothalamic and extra-hypothalamic systems. Moreover, during the postnatal period when MS is typically administered, the BNST undergoes critical neural developmental events. This review highlights evidence that MS interferes with neural development to permanently alter BNST circuitry, which may account for a variety of behavioral deficits seen following early life stress.

This article is part of the Special Issue on ‘Fear, Anxiety and PTSD’.