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 Previous Article
Volume 17, Number 16,
Issue of August 15, 1997
pp. 6483-6491
Copyright ©1997 Society for Neuroscience
Low-Frequency Stimulation of Afferent A -Fibers Induces
Long-Term Depression at Primary Afferent Synapses with Substantia
Gelatinosa Neurons in the Rat
Received May 5, 1997; accepted June 4, 1997.
J. Sandkühler1, 2,
J. G. Chen2,
G. Cheng1, and
M. Randi 1
1 Department of Veterinary Physiology and Pharmacology,
Iowa State University, Ames, Iowa 50011, and 2 Institute of
Physiology II, University of Heidelberg, 69120 Heidelberg, Germany
Impulses in primary afferent nerve fibers may produce short- or
long-lasting modifications in spinal nociception. Here we have
identified a robust long-term depression (LTD) of synaptic transmission
in substantia gelatinosa neurons that can be induced by low-frequency
stimulation of primary afferent A -fibers. Synaptic transmission
between dorsal root afferents and neurons in the substantia gelatinosa
of the spinal cord dorsal horn was examined by intracellular recording
in a transverse slice dorsal root preparation of rat spinal cord.
Conditioning stimulation of dorsal roots with 900 pulses given at 1 Hz
(10 V, 0.1 msec) produced LTD of EPSP amplitudes in substantia
gelatinosa neurons to 41 ± 10% of control that lasted for at
least 2 hr. When A- and C-fibers were recruited, conditioning
stimulation was as effective as A-fiber stimulation alone. After LTD,
synaptic strength could be increased to its original level by applying
a second, high-frequency tetanic stimulus to the dorsal root,
indicating that LTD is reversible and not attributable to damage of
individual synapses. Bath application of the GABAA receptor
antagonist bicuculline and glycine receptor antagonist strychnine did
not affect LTD. When NMDA receptors were blocked by bath application of
D-2-amino-5-phosphonovaleric acid, LTD was abolished or
strongly reduced. Loading substantia gelatinosa neurons with
Ca2+ chelator BAPTA also blocked or reduced LTD.
After incubation of slices with calyculin A, a selective and membrane
permeable inhibitor of protein phosphatases 1 and 2A, LTD was not
attenuated. We propose that this form of LTD may be relevant for
long-lasting segmental antinociception after afferent stimulation.
Key words:
primary afferents;
synaptic transmission;
spinal cord;
substantia gelatinosa;
pain;
antinociception;
afferent stimulation;
long-term depression;
NMDA;
BAPTA;
calyculin A
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