Abstract
The acoustic startle reflex in rats can be inhibited if a prepulse stimulus is presented just before the startle stimulus (prepulse inhibition; PPI). When postnatal day 7 (P7) rats are exposed to agents that block the NMDA receptor (NMDAR), robust apoptosis is observed within hours and is thought to be followed at later ages by a significant loss of PPI. To understand these observations further, we exposed rat pups to vehicle or the NMDAR antagonist MK801 (1 mg/kg) at P6, P8, and P10. We then examined animals for PPI at P28 and P56. Compared to vehicle controls, we found no evidence for PPI deficits in the MK801-treated group, although we did observe prepulse-induced delay in response time at P56 (but not at P28). In a parallel study, we also performed histological analysis of brain sections for evidence of the pro-apoptotic marker activated caspase-3, 8 h after vehicle or MK801 injection into P6 animals. We found that there was a robust increase in this marker of cell death in the inferior colliculus of MK801 compared to vehicle-treated animals. Thus, transient blockade of the NMDAR during the postnatal period not only promotes early apoptosis in a brain region critical for acoustic processing but also leads to auditory deficits at a later age, suggesting that injury-induced loss of collicular neurons leads to network reorganization in the auditory system that is progressive in nature.
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Acknowledgments
The authors are indebted to Jody Roberts for her technical support and training efforts in establishing the PPI behavioral assay. These studies were supported by NIH RO1 051632 and a Wake Forest University Cross Campus Collaboration Research Support Fund grant to CPT and TDB. Immunohistochemistry performed by CL, image analysis and cell counts by CL and CPT, acoustic startle (PPI) assay performed by AL and JS, and data analysis by AL, JS, TDB, and CPT. Manuscript preparation by AL, TDB, and CPT.
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A. Lyall and J. Swanson are co-first authors.
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Lyall, A., Swanson, J., Liu, C. et al. Neonatal exposure to MK801 promotes prepulse-induced delay in startle response time in adult rats. Exp Brain Res 197, 215–222 (2009). https://doi.org/10.1007/s00221-009-1906-2
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DOI: https://doi.org/10.1007/s00221-009-1906-2