Early life experience shapes the functional organization of stress-responsive visceral circuits

Abstract

Emotions are closely tied to changes in autonomic (i.e., visceral motor) function, and interoceptive sensory feedback from body to brain exerts powerful modulatory control over motivation, affect, and stress responsiveness. This manuscript reviews evidence that early life experience can shape the structure and function of central visceral circuits that underlie behavioral and physiological responses to emotive and stressful events. The review begins with a general discussion of descending autonomic and ascending visceral sensory pathways within the brain, and then summarizes what is known about the postnatal development of these central visceral circuits in rats. Evidence is then presented to support the view that early life experience, particularly maternal care, can modify the developmental assembly and structure of these circuits in a way that impacts later stress responsiveness and emotional behavior. The review concludes by presenting a working hypothesis that endogenous cholecystokinin signaling and subsequent recruitment of gastric vagal sensory inputs to the caudal brainstem may be an important mechanism by which maternal care influences visceral circuit development in rat pups. Early life experience may contribute to meaningful individual differences in emotionality and stress responsiveness by shaping the postnatal developmental trajectory of central visceral circuits.

Figure 1

Endogenous CCK released from the gut during milk digestion in neonatal rats activates vagal sensory inputs to the caudal medulla (DVC) through a CCK-1 receptor-mediated mechanism. We hypothesize that vagal sensory signals can interact within the DVC with other somatosensory and visceral sensory signals ascending from the spinal cord via the spino-solitary tract, including signals generated by maternal licking and grooming of the rat pup. These signals may thereby modulate the functional development of ascending and reciprocated descending projections between the DVC and hypothalamic and limbic forebrain regions that modulate physiological and behavioral responses of the animal to its internal and external environments. Circles and lines are meant to represent key circuit nodes and connections among them, although the representation is not all-inclusive. Abbreviations as in the text.