Early Life Experience Alters Stress-related Brain Circuits: Effects of Repeated Brief Postnatal Maternal Separation on Central Autonomic Pathways

Early life experience has a powerful influence on later stress reactivity, which is demonstrated by the animal model, repeated brief postnatal maternal separation. In this classic paradigm, rat pups undergo a 15-minute daily separation (MS15) from their dam for approximately one to two postnatal weeks. A substantial literature has demonstrated that adult rats with a developmental history of MS15 are significantly less stress reactive compared to controls, as evidenced by decreased stress-induced hormone release. Conversely, the effects of early life experience on brain circuits that control stress responses are virtually unknown. Descending preautonomic circuits govern the output of the autonomic nervous system, which mediates physiological responses to stress (e.g., increased heart rate and decreased digestion). These circuits begin in the paraventricular nucleus of the hypothalamus (PVN) and limbic forebrain and synaptically innervate preganglionic neurons in the brainstem dorsal vagal complex (DVC) and spinal cord that ultimately innervate body organs. A previous study from our laboratory has demonstrated that MS15 alters the developmental assembly of gastric preautonomic circuits (Card et al., 2005). These findings led us to hypothesize that MS15 rats would display altered circuit strength of gastric preautonomic circuits later in development, as assessed in juvenile rats. Indeed, the study described in Chapter 2 demonstrated that MS15 enhances the circuit strength of gastric preautonomic circuits originating within the PVN in juvenile rats. This enhanced circuit strength suggests that the function of preautonomic PVN pathways might also be altered by MS15. Thus, we hypothesized that MS15 rats would display altered stress-induced activation of the PVN to DVC pathway. The study described in Chapter 3 revealed that MS15 rats display decreased stress-induced Fos activation within the PVN and within a specific population of DVC neurons. Therefore, studies within this dissertation revealed that M15 alters the circuit strength of PVN preautonomic pathways and alters stress-induced activation of brainstem preautonomic pathways. These findings suggest that MS15 rats would display attenuated autonomic responses to stress and may provide insights into how early life experience shapes later stress reactivity