In neocortex glutamate activates ionotropic and metabotropic receptors (mGl
uRs). Whole-cell current-clamp recordings in the in vitro rat auditory cort
ex at 32 degreesC were used to explore the role that mGluRs have in regulat
ion of AMPA/kainate, NMDA, and GABA receptor-mediated synaptic transmission
. Our findings are: (a) The fast EPSP (AMPA/kainate), slow EPSP (NMDA), and
IPSPs (GABA(A), GABA(B)), elicited in pyramidal neurons are reduced in the
presence of (1S,3R)- ACPD (mGluR agonist) with greatest effect on the slow
IPSP>fast IPSP>>fast EPSP. The effect is likely the result of ACPD acting
at presynaptic mGluRs because the probability of release of glutamate and G
ABA is reduced in the presence of ACPD, intracellular infusion of a G prote
in antagonist (GDP betaS) did not block the effect of ACPD, nor were iontop
horetic kainic acid or NMDA-induced depolarizations reduced by ACPD. (b) Th
e slow EPSP is enhanced following washout of ACPD and enhancement is not du
e to disinhibition because it is present in the absence of IPSPs, but if IP
SPs are present, its magnitude can be influenced. Iontophoretic NMDA respon
ses are enhanced in the presence of ACPD, an effect blocked by GDP betaS an
d heparin (intracellular inositol 1,4,5-trisphosphate receptor antagonist).
Taken together, this evidence suggests that enhancement is a result of gro
up I postsynaptic mGluR activation. (c) In fast-spiking cells ACPD reduces
the EPSP (AMPA/kainate and NMDA-mediated). This action is likely presynapti
c because it persists when GDP betaS is in the cells. (d) The rate of spike
discharge recorded from fast-spiking cells is accelerated in ACPD but does
not change in the presence of GDP betaS, suggesting a postsynaptic effect.
Our data indicate that mGluRs can influence neocortical synaptic transmiss
ion in complex ways by acting presynaptically and postsynaptically.