Related Experiment Videos
Activation of NMDA receptors stimulates extracellular proteolysis of cell adhesion molecules in hippocampus
K B Hoffman1, J Larson, B A Bahr
1Ancile Pharmaceuticals, 1250 Prospect St., Suite #202, La Jolla, CA 92037, USA.
Abstract:
Recent work indicates that treatments which block adhesion receptors prevent the stabilization of long term potentiation (LTP). The experiments reported here show that brief stimulation of hippocampal NMDA receptors, a triggering event for LTP induction, results in the extracellular proteolysis of two or more members of the Cell Adhesion Molecule (CAM) family. This effect is rapid, occurs at a consensus serine protease site, and is selective to NMDA receptors. It is also found in vivo after kainic acid induced seizures. Cleavage of adhesive connections could be an early step in the formation of new synaptic configurations.
Insights
Blocking cell adhesion molecules (CAMs) prevents long-term potentiation (LTP) stabilization. NMDA receptor stimulation triggers CAM proteolysis, a key step in synaptic plasticity and new configurations.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Long-term potentiation (LTP) stabilization is crucial for memory formation.
- Adhesion receptors play a role in LTP stabilization, as blocking them prevents this process.
Purpose of the Study:
- To investigate the effect of hippocampal NMDA receptor stimulation on Cell Adhesion Molecules (CAMs).
- To determine if proteolysis of CAMs is an early event in LTP induction.
Main Methods:
- Stimulation of hippocampal NMDA receptors.
- Analysis of extracellular proteolysis of CAMs.
- In vivo experiments using kainic acid-induced seizures.
Main Results:
- Brief stimulation of hippocampal NMDA receptors induced rapid extracellular proteolysis of CAMs.
- Proteolysis occurred at a consensus serine protease site and was selective to NMDA receptors.
- Similar CAM cleavage was observed in vivo following kainic acid-induced seizures.
Conclusions:
- NMDA receptor activation triggers CAM proteolysis, suggesting a novel mechanism in synaptic plasticity.
- Cleavage of cell adhesion molecules may be an early, critical step in the formation of new synaptic configurations during LTP.