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Updated: Jun 22, 2026
Habituation and Prepulse Inhibition of Acoustic Startle in Rodents
Published on: September 1, 2011
Neonatal exposure to MK801 promotes prepulse-induced delay in startle response time in adult rats
Amanda Lyall1, John Swanson, Chun Liu
1Department of Neurobiology and Anatomy, 4100 Gray Bldg, Wake Forest University School of Medicine, 1 Medical Center Blvd, Winston Salem, NC 27157-1010, USA.
Insights
Blocking NMDA receptors in young rats causes cell death in auditory processing areas. This early injury leads to progressive auditory deficits later in life, impacting acoustic startle reflex responses.
Area of Science:
- Neuroscience
- Developmental Biology
- Auditory System Research
Background:
- Prepulse inhibition (PPI) of the acoustic startle reflex is a measure of sensorimotor gating.
- NMDA receptor (NMDAR) blockade during development can cause apoptosis and may affect later PPI.
- The inferior colliculus is a key brain region for auditory processing.
Purpose of the Study:
- To investigate the long-term effects of early-life NMDAR blockade on PPI in rats.
- To determine if early apoptosis in the inferior colliculus correlates with later auditory deficits.
Main Methods:
- Postnatal rat pups (P6, P8, P10) were treated with MK801 (NMDAR antagonist) or vehicle.
- Prepulse inhibition (PPI) was assessed at P28 and P56.
- Histological analysis for activated caspase-3 (a marker of apoptosis) was performed 8 hours post-injection in P6 animals.
Main Results:
- MK801 treatment did not cause PPI deficits at P28 or P56.
- A prepulse-induced delay in response time was observed at P56 in the MK801 group.
- Increased activated caspase-3 was found in the inferior colliculus of MK801-treated animals.
Conclusions:
- Transient NMDAR blockade during early development induces apoptosis in the inferior colliculus.
- Early apoptotic injury in this auditory region leads to progressive, long-term auditory deficits.
- These findings suggest developmental auditory system injury can cause adaptive network reorganization.
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.
