Hidden talents: Poly (I:C)-induced maternal immune activation improves mouse visual discrimination performance and reversal learning in a sex-dependent manner

Genes Brain Behav. 2021 Sep;20(7):e12755. doi: 10.1111/gbb.12755. Epub 2021 Jun 17.


While there is a strong focus on the negative consequences of maternal immune activation (MIA) on developing brains, very little attention is directed towards potential advantages of early life challenges. In this study, we utilized a polyinosine-polycytidylic acid (poly(I:C)) MIA model to test visual pairwise discrimination (PD) and reversal learning (RL) in mice using touchscreen technology. Significant sex differences emerged in that MIA reduced the latency for males to make a correct choice in the PD task while females reached criterion sooner, made fewer errors, and utilized fewer correction trials in RL compared to saline controls. These surprising improvements were accompanied by the sex-specific upregulation of several genes critical to cognitive functioning, indicative of compensatory plasticity in response to MIA. In contrast, when exposed to a 'two-hit' stress model (MIA + loss of the social component of environmental enrichment [EE]), mice did not display anhedonia but required an increased number of PD and RL correction trials. These animals also had significant reductions of CamK2a mRNA in the prefrontal cortex. Appropriate functioning of synaptic plasticity, via mediators such as this protein kinase and others, are critical for behavioral flexibility. Although EE has been implicated in, delaying the appearance of symptoms associated with certain brain disorders, these findings are in line with evidence that it also makes individuals more vulnerable to its loss. Overall, with the right 'dose', early life stress exposure can confer at least some functional advantages, which are lost when the number or magnitude of these exposures become too great.

Keywords: acetylcholine; cognitive flexibility; companion loss; compensatory mechanisms; fetal programming; hippocampus; parvalbumin; perineuronal nets; prefrontal cortex; prenatal immune activation; sex differences; social isolation; two-hit.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Attention / drug effects
  • Behavior, Animal / physiology
  • Cognition / drug effects
  • Discrimination, Psychological / drug effects*
  • Disease Models, Animal
  • Female
  • Mice
  • Poly I-C / pharmacology*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / immunology
  • Prenatal Exposure Delayed Effects / physiopathology
  • Reversal Learning / drug effects*
  • Sex Factors*
  • Visual Perception / drug effects
  • Visual Perception / immunology*
  • Visual Perception / physiology


  • Poly I-C