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Desensitization of AMPA Receptors Limits the Amplitude of EPSPs and the Excitability of Motoneurons of the Rat Isolated Spinal Cord
Author(s) -
Ballerini Laura,
Bracci Enrico,
Nistri Andrea
Publication year - 1995
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1995.tb01113.x
Subject(s) - ampa receptor , excitatory postsynaptic potential , desensitization (medicine) , neuroscience , chemistry , tetrodotoxin , spinal cord , postsynaptic potential , cnqx , bursting , biophysics , stimulation , glutamate receptor , receptor , biology , biochemistry , inhibitory postsynaptic potential
Intracellular recording was used to study the effect of cyclothiazide, a selective blocker of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA) receptor desensitization, on lumbar motoneurons of the rat isolated spinal cord. Cyclothiazide (25 μM) enhanced the responses to AMPA in a tetrodotoxin‐insensitive fashion, without affecting those produced by N ‐methyl‐D‐aspartate or γ‐aminobutyric acid. Excitatory postsynaptic potentials (EPSPs) evoked by dorsal root stimulation were strongly potentiated in amplitude while paired‐pulse depression (produced by applying pairs of pulses at 2 s interval) of the EPSP was decreased. In the presence of cyclothiazide the frequency of spontaneous synaptic events was greatly increased and network‐driven bursting activity developed with eventual loss of electrical excitability. The present results suggest that pharmacological block of AMPA receptor desensitization led to strong excitation of motoneurons and indicate a physiological role of desensitization in protecting these nerve cells from overactivity.