Long-term regulation of n-methyl-d-aspartate receptor subunits and associated synaptic proteins following hippocampal synaptic plasticity

Autor: Joanna M. Williams, Diane Guévremont, Warren P. Tate, Sara E. Mason-Parker, Jeremy T. T. Kennard, Wickliffe C. Abraham
Rok vydání: 2003
Předmět:
Male
medicine.medical_specialty
N-Methylaspartate
Time Factors
Blotting
Western

Long-Term Potentiation
Nonsynaptic plasticity
Nerve Tissue Proteins
Nitric Oxide Synthase Type I
AMPA receptor
In Vitro Techniques
Biology
Hippocampus
Receptors
N-Methyl-D-Aspartate

Rats
Sprague-Dawley

Internal medicine
Synaptic augmentation
medicine
Animals
Long-term depression
Neuronal Plasticity
musculoskeletal
neural
and ocular physiology

General Neuroscience
Excitatory Postsynaptic Potentials
Long-term potentiation
Electric Stimulation
Rats
Cell biology
Electrophysiology
Microscopy
Electron

Synaptic fatigue
Endocrinology
nervous system
Calcium-Calmodulin-Dependent Protein Kinases
Synapses
Synaptic plasticity
NMDA receptor
Dizocilpine Maleate
Nitric Oxide Synthase
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Excitatory Amino Acid Antagonists
Synaptosomes
Zdroj: Neuroscience. 118:1003-1013
ISSN: 0306-4522
DOI: 10.1016/s0306-4522(03)00028-9
Popis: Synaptic plasticity in the dentate gyrus is dependent on activation of the N -methyl- d -aspartate (NMDA)-subtype of glutamate receptors. In this study, we show that synaptic plasticity in turn regulates NMDA receptors, since subunits of the NMDA receptor complex are bidirectionally and independently regulated in the dentate gyrus following activation of perforant synapses in awake animals. Low-frequency stimulation that produced a mild synaptic depression resulted in a decrease in the NMDA receptor subunits NR1 and NR2B 48 h following stimulation. High-frequency stimulation that produced long-term potentiation resulted in an increase in NR1 and NR2B at the same time point. Further investigations revealed that in contrast to NR2B, NR1 levels increased gradually after long-term potentiation induction, reaching a peak level at 48 h, and were insensitive to the competitive NMDA receptor antagonist 3-3(2-carboxypiperazin-4-yl) propyl-1-phosphate. The increased levels of NR1 and NR2B at 48 h were found associated with synaptic membranes and with increased NMDA receptor-associated proteins, postsynaptic density protein 95, neuronal nitric oxide synthase and Ca 2+ /calmodulin-dependent protein kinase II, α subunit. These data suggest that the persistence of long-term potentiation is associated with an increase in the number of NMDA receptor complexes, which may be indicative of an increase in synaptic contact area.
Databáze: OpenAIRE