Multigenerational prenatal stress increases the coherence of brain signaling among cortico-striatal-limbic circuits in adult rats

Prenatal stress (PNS) is a significant risk factor for the development of psychopathology in adulthood such as anxiety, depression, schizophrenia and addiction. Animal models of PNS resemble many of the effects of PNS on humans and provide a means to study the accumulated effects of PNS over several generations on brain function. Here, we examined how mild PNS delivered during the third week in utero over four consecutive generations affects behavioral flexibility and functional signaling among cortical and limbic structures. These multi-generational prenatally stressed (MGPNS) rats were not impaired on an odor-cued reversal learning task as compared to control animals. Unilateral field potential (FP) recordings from the medial prefrontal cortex, basolateral amygdala, ventral hippocampus, and striatal territories revealed widespread differences in brain signaling between these groups during the odor sampling phase of the task. The FP power was significantly lower in most structures across most frequency bands in MGPNS animals, and the relative increase in power from baseline during the task was lower for the beta band (12-30 Hz) in MGPNS animals as compared to controls. The coherence of FPs between brain regions, however, was much higher in MGPNS animals among all structures and for most frequency bands. We propose that this pattern of changes in brain signaling reflects a simplification of network processing, which is consistent with reports of reduced spine density and dendritic complexity in the brains of animals receiving PNS. Our data support the proposal that recurrent ancestral stress leads to adaptations in the brain, and that these may confer adaptive behavior in some circumstances as compared to single-generation PNS.