Altered object-in-place recognition memory, prepulse inhibition, and locomotor activity in the offspring of rats exposed to a viral mimetic during pregnancy

doi:10.1016/j.neuroscience.2011.11.011

Neuroscience

Volume 201, 10 January 2012, Pages 184-198

https://doi.org/10.1016/j.neuroscience.2011.11.011 Get rights and content

Abstract

Infection during pregnancy (i.e., prenatal infection) increases the risk of psychiatric illnesses such as schizophrenia and autism in the adult offspring. The present experiments examined the effects of prenatal immune challenge on behavior in three paradigms relevant to these disorders: prepulse inhibition (PPI) of the acoustic startle response, locomotor responses to an unfamiliar environment and the N-methyl-d-aspartate antagonist MK-801, and three forms of recognition memory. Pregnant Long–Evans rats were exposed to the viral mimetic polyinosinic-polycytidylic acid (PolyI:C; 4 mg/kg, i.v.) on gestational day 15. Offspring were tested for PPI and locomotor activity before puberty (postnatal days (PNDs)35 and 36) and during young adulthood (PNDs 56 and 57). Four prepulse-pulse intervals (30, 50, 80, and 140 ms) were employed in the PPI test. Recognition memory testing was performed using three different spontaneous novelty recognition tests (object, object location, and object-in-place recognition) after PND 60. Regardless of sex, offspring of PolyI:C-treated dams showed disrupted PPI at 50-, 80-, and 140-ms prepulse-pulse intervals. In the prepubescent rats, we observed prepulse facilitation for the 30-ms prepulse-pulse interval trials that was selectively retained in the adult PolyI:C-treated offspring. Locomotor responses to MK-801 were significantly reduced before puberty, whereas responses to an unfamiliar environment were increased in young adulthood. Both male and female PolyI:C-treated offspring showed intact object and object location recognition memory, whereas male PolyI:C-treated offspring displayed significantly impaired object-in-place recognition memory. Females were unable to perform the object-in-place test. The present results demonstrate that prenatal immune challenge during mid/late gestation disrupts PPI and locomotor behavior. In addition, the selective impairment of object-in-place recognition memory suggests tasks that depend on prefrontal cortex may be particularly vulnerable following prenatal immune challenge.

Highlights

▶Behavioral effects of prenatal PolyI:C treatment were examined in both male and female prepubescent and adult Long Evans rats. ▶Disrupted prepulse inhibition and locomotor activity were observed in male and female offspring exposed to PolyI:C. ▶Neither object nor object location recognition memory was altered by prenatal exposure to PolyI:C. ▶Prefrontal-dependent object-in-place memory was severely disrupted in adult male offspring exposed to PolyI:C.

Section snippets

Subjects

Timed pregnant Long–Evans dams (GD 7; Charles River Laboratories, Quebec, Canada) were singly housed in transparent plastic cages in a temperature-controlled (21 °C) colony room on a 12/12-h light/dark cycle with food (Purina Rat Chow) and water available ad libitum. The offspring of four separate squads of dams purchased between January 2010 and January 2011 were used in the present experiments. Some animals were siblings of those reported in Zhang et al. (in press). Maternal observations were

Effects of PolyI:C treatment on dams and pups

Weight and rectal temperature of all dams were taken 0, 8, 24, and 48 h following PolyI:C injection. Human error resulted in the loss of weight data for one dam and temperature data for five dams. Statistical analysis of dam weights revealed significant main effects of Time (F(3,87)=45.72, P<0.001), Treatment (F(1,29)=5.11, P=0.031), and a significant Treatment by Time interaction (F(3,87)=17.28, P<0.001). Inspection of the data revealed that dam weights were significantly lower for the saline

Discussion

The present study examined the influence of prenatal immune challenge with PolyI:C on PPI of the acoustic startle response, locomotor activity, and recognition memory in Long Evans rats. Consistent with previous reports, PolyI:C treatment caused significant weight loss in the dams and a subtle increase in temperature (Fig. 1). With prepulse-pulse intervals of 50, 80, and 140 ms, PolyI:C treatment disrupted PPI before puberty and in young adulthood (Fig. 2). Enhanced prepulse facilitation was

Conclusion

The present experiments demonstrate that prenatal immune challenge results in cognitive and behavioral disruptions in rats similar to those reported in patients with neurodevelopmental psychiatric disorders such as schizophrenia. The specificity of the recognition memory deficit to the object-in-place test suggests that cognitive functions associated with the prefrontal cortex may be particularly susceptible to alteration following prenatal infection. The relative ease of conducting these tasks

Acknowledgments

The present work was supported by a Young Investigator Award from the National Alliance for Research on Schizophrenia and Depression, Saskatchewan Health Research Foundation New Investigator Award, and University of Saskatchewan Molstad Trust Intramural Research Award to J.G.H. B.N.C. is the recipient of a National Sciences and Engineering Research Council of Canada Graduate Scholarship. We would like to thank Chester Thai and Quentin Greba for technical assistance with these experiments.

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Cognitive, Behavioral, and Systems NeuroscienceResearch PaperAltered object-in-place recognition memory, prepulse inhibition, and locomotor activity in the offspring of rats exposed to a viral mimetic during pregnancy

Abstract

Highlights

Section snippets

Subjects

Effects of PolyI:C treatment on dams and pups

Discussion

Conclusion

Acknowledgments

Biol Psychiatry

Prog Neuropsychopharmacol Biol Psychiatry

Behav Brain Res

Pharmacol Biochem Behav

Psychiatry Res

Behav Brain Res

Int Rev Neurobiol

Behav Brain Res

Behav Brain Res

J Psychiatr Res

Behav Brain Res

Neurobiol Learn Mem

Neurotoxicol Teratol

Neurobiol Learn Mem

Behav Brain Res

Behav Brain Res

Brain Behav Immun

Biol Psychiatry

Neurosci Res

Brain Behav Immun

Prog Neurobiol

Behav Brain Res

Prog Neurobiol

Neurosci Biobehav Rev

Neurosci Biobehav Rev

Brain Behav Immun

Biol Psychiatry

Behav Brain Res

Biol Psychiatry

Biol Psychiatry

Brain Res Bull

J Psychiatr Res

Neurosci Lett

Behav Brain Res

Behav Brain Res

Behav Brain Res

Biol Psychiatry

Pharmacol Ther

J Psychiatr Res

Daily functioning and information-processing skills among persons with schizophrenia

Psychiatr Serv

Recognition memory for objects, place, and temporal order: a disconnection analysis of the role of the medial prefrontal cortex and perirhinal cortex

J Neurosci

Cognitive, Behavioral, and Systems Neuroscience
Research Paper
Altered object-in-place recognition memory, prepulse inhibition, and locomotor activity in the offspring of rats exposed to a viral mimetic during pregnancy