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The Journal of Neuroscience, January 15, 2001, 21(2):741-749
Intensity-Dependent, Rapid Activation of Presynaptic Metabotropic
Glutamate Receptors at a Central Synapse
Gautam B.
Awatramani and
Malcolm M.
Slaughter
Department of Physiology and Biophysics and Department of
Ophthalmology, State University of New York, Buffalo, New York
14214
Synaptic signals from retinal bipolar cells were monitored by
measuring EPSCs in ganglion cells voltage-clamped at 70 mV. Spontaneous EPSCs were strongly suppressed by
L-2-amino-4-phosphonobutyrate (AP-4), an agonist at
group III metabotropic glutamate receptors (mGluRs). Agonists of group
I or II mGluRs were ineffective. AP-4 also suppressed ganglion cell
EPSCs evoked by bipolar cell stimulation using potassium puffs, sucrose
puffs, or zaps of current (0.5-1 µA). In addition, AP-4 suppressed
Off EPSCs evoked by dim-light stimuli. This indicates that group III
mGluRs mediate a direct suppression of bipolar cell transmitter
release. An mGluR antagonist, (RS)- -cyclopropyl-4-phosphonophenylyglycine (CPPG),
blocked the action of AP-4. When bipolar cells were weakly stimulated,
AP-4 produced a large suppression of the EPSC, but CPPG alone had
little effect. Conversely, when bipolar cells were strongly stimulated, CPPG produced an enhancement of the EPSC, but AP-4 alone had little effect. This indicates that endogenous feedback regulates bipolar cell
transmitter release and that the dynamic range of the presynaptic metabotropic autoreceptor is similar to that of the postsynaptic ionotropic receptor. Furthermore, the feedback is rapid and
intensity-dependent. Hence, concomitant activation of presynaptic and
postsynaptic glutamate receptors shapes the responses of ganglion cells.
Key words:
synaptic transmission; retina; bipolar cell; AP-4; CPPG; ganglion cell
Copyright © 2001 Society for Neuroscience 0270-6474/01/212741-09$05.00/0
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