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Long-lasting synaptic modification in the rat hippocampus resulting from NMDA receptor blockade during development
Frederick P Bellinger1, Peter A Wilce, Kuldip S Bedi
1Alcohol Research Unit, Department of Biochemistry, The University of Queensland, St. Lucia, QLD 4072, Australia. bellinger@brain.riken.go.jp
Synapse (New York, N.Y.)
|January 5, 2002
Summary
Neonatal exposure to NMDA receptor antagonists impairs synapse development in the hippocampus. This suggests N-methyl-D-aspartate receptor activation is crucial for healthy synaptic maturation.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Synaptic Plasticity
Background:
- Proper synapse maturation in the hippocampus is linked to NMDA receptor activation.
- Neonatal ethanol exposure causes lasting reductions in hippocampal synaptic strength.
Purpose of the Study:
- To investigate if neonatal NMDA receptor antagonist administration causes lasting synaptic changes.
- To determine the necessity of NMDA receptor activation for proper synaptic development.
Main Methods:
- Neonatal rats (PND 4-9) received daily injections of NMDA receptor antagonists (MK-801, CPP) or AMPA receptor antagonist (NBQX).
- Control groups received saline or no treatment.
- Hippocampal slices were prepared from PND 35-40 for electrophysiological analysis.
Main Results:
- NMDA receptor antagonist treatment led to reduced synaptic efficacy, requiring higher stimulus currents for comparable responses.
- Key synaptic function ratios were decreased in NMDA antagonist-treated animals.
- No significant changes were observed in AMPA antagonist-treated animals or in long-term potentiation/paired-pulse facilitation.
Conclusions:
- NMDA receptor activation during development is essential for the proper maturation of hippocampal synapses.
- Disruption of NMDA receptor function in neonates has lasting negative effects on synaptic properties.