Metabotropic glutamate receptors (mGluRs) regulate transmitter release
at mammalian central synapses. However, because oi the difficulty of
recording from mammalian presynaptic terminals, the mechanism underlyi
ng mGluR-mediated presynaptic inhibition is not known. Here, simultane
ous recordings from a giant presynaptic terminal, the calyx of Held, a
nd its postsynaptic target in the medial nucleus of the trapezoid body
were obtained in rat brainstem slices. Agonists of mGluRs suppressed
a high voltage-activated P/Q-type calcium conductance in the presynapt
ic terminal, thereby inhibiting transmitter release at this glutamater
gic synapse. Because several forms of presynaptic modulation and plast
icity are mediated by mGluRs, this identification of a target ion chan
nel is a first step toward elucidation of their molecular mechanism.