Repeated brief postnatal maternal separation enhances hypothalamic gastric autonomic circuits in juvenile rats

Abstract

Maternal separation of rat pups for 15 minutes each day over the first one to two postnatal weeks (MS15) has been shown to increase the active maternal care received by pups and to decrease their later neuroendocrine and behavioral stress reactivity compared to non-separated (NS) controls. Stress responses prominently feature altered gastric secretion and motility, and we previously reported that the developmental assembly of forebrain circuits underlying gastric autonomic control, including gastric responses to stress, is delayed by MS15 in neonatal rats (Card et al. 2005, J. Neurosci. 25(40): 9102). To determine how this early delay affects the later organization of central gastric autonomic circuits, the present study examined the effects of neonatal MS15 on central pre-gastric circuits assessed in post-weaning, juvenile rats. For this purpose, the retrograde transynaptic viral tracer, pseudorabies virus (PRV), was microinjected into the stomach wall of 28-30 day old male rats with an earlier developmental history of either MS15 or NS. Rats were perfused 72 hours later and tissue was processed to reveal PRV-positive cells. Transynaptic PRV immunolabeling was quantified in selected preautonomic brainstem and forebrain regions, including the area postrema, bed nucleus of the stria terminalis, central nucleus of the amygdala, paraventricular nucleus of the hypothalamus (PVN), and visceral cortices. Compared to NS controls, MS15 rats displayed a significantly greater amount of PRV labeling within the PVN, including both the dorsal cap and ventral subnuclei. There were no postnatal group differences in the amount of PRV labeling within any other brain region examined in this study. This effect of MS15 to enhance hypothalamic preautonomic circuit structure indicates a strengthening of this pathway and may provide insight into how early life experience produces differential effects on later stress reactivity, including gastric secretory and motor responses to stress.

Early experience alters limbic forebrain Fos responses to a stressful interoceptive stimulus in young adult rats

“…Our results, showing differential levels of dorsal BNST Fos activation in response to LiCl treatment across all three rearing groups, suggest that dorsal BNST responsiveness to an interoceptive challenge is altered, in addition to circuit anatomy. More recently, Banihashemi and Rinaman [54] demonstrated increased numbers of gastric pre-autonomic neurons in the PVN in adolescent rats with a developmental history of MS-15, further evidence that central visceral circuits can be altered by early postnatal experience.…”

Electrophysiological insights into the enduring effects of early life stress on the brain

“…These are part of a larger literature showing effects of early life experience, including stress, on later autonomic control of various systems, notably respiratory, cardiovascular, and gastrointestinal systems (Banihashemi and Rinaman 2009;Chung et al 2007;Gue et al 1997;Sanders and Anticevic 2007;Welting et al 2005). However, if we consider only studies that directly measure some aspect of electrophysiological function in autonomic circuitry, only respiratory function has been studied in this way.…”

Muscimol microinjection into cerebellar fastigial nucleus exacerbates stress-induced gastric mucosal damage in rats

“…In a previous study [36] , an altered ability of the hypothalamus was suggested to modulate gastric function, including the secretory and motor responses to stress. In agreement with that idea, we also detected alterations in gastric juice volume and acidity.…”