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Isolated NMDA receptor-mediated synaptic responses express both LTP and LTD
X Xie1, T W Berger, G Barrionuevo
1Department of Behavioral Neuroscience, University of Pittsburgh, Pennsylvania 15260.
Journal of Neurophysiology
|April 1, 1992
Summary
This study shows that N-methyl-D-aspartate (NMDA) receptor activity in the hippocampus can be modified long-term. Specific electrical stimulation patterns and calcium levels are crucial for inducing long-term potentiation (LTP) or depression (LTD).
Area of Science:
- Neuroscience
- Synaptic Plasticity
- Hippocampal Function
Background:
- N-methyl-D-aspartate (NMDA) receptors are crucial for synaptic plasticity.
- Understanding the conditions that modify NMDA receptor-mediated transmission is key to understanding learning and memory.
Purpose of the Study:
- To investigate use-dependent, long-lasting modifications of NMDA receptor-mediated synaptic transmission in the hippocampal dentate gyrus.
- To determine the role of membrane potential and intracellular calcium ([Ca2+]i) in inducing these modifications.
Main Methods:
- Intracellular recordings from hippocampal dentate gyrus granule cells in vitro.
- Pharmacological isolation of NMDA receptor-mediated transmission using CNQX.
- Induction of synaptic plasticity using high (50 Hz) and low (10 Hz) frequency tetanic stimulation.
- Manipulation of granule cell membrane potential and intracellular calcium buffering (BAPTA).
Main Results:
- Robust long-term potentiation (LTP) of NMDA receptor-mediated synaptic potentials was induced by 50 Hz and 10 Hz tetanic stimuli.
- Hyperpolarization during 50 Hz stimulation blocked LTP induction, indicating a need for simultaneous pre- and postsynaptic activation.
- Hyperpolarization during 10 Hz stimulation induced long-term depression (LTD).
- Intracellular calcium buffering with BAPTA blocked LTP and partially blocked LTD induction.
Conclusions:
- Simultaneous pre- and postsynaptic activation is a prerequisite for NMDA receptor-mediated LTP.
- Different patterns of stimulation and altered intracellular calcium levels can lead to either LTP or LTD.
- These findings highlight the complex mechanisms underlying synaptic plasticity in the hippocampus.