Excitatory postsynaptic potentials in rat neocortical neurons in vitro. III. Effects of a quinoxalinedione non-NMDA receptor antagonist

1. Intracellular microelectrodes were used to obtain recordings
from neurons in layer II/III of rat frontal cortex. A bipolar
electrode positioned in layer IV of the neocortex was used to evoke
postsynaptic potentials. Graded series of stimulation were employed
to selectively activate different classes of postsynaptic
responses. The sensitivity of postsynaptic potentials and
iontophoretically applied neurotransmitters to the
non-N-methyl-D-asparate (NMDA) antagonist
6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) was examined. 2. As
reported previously, low-intensity electrical stimulation of
cortical layer IV evoked short-latency early excitatory
postsynaptic potentials (eEPSPs) in layer II/III neurons. CNQX
reversibly antagonized eEPSPs in a dose-dependent manner.
Stimulation at intensities just subthreshold for activation of
inhibitory postsynaptic potentials (IPSPs) produced long-latency
(10 to 40-ms) EPSPs (late EPSPs or 1EPSPs). CNQX was effective in
blocking 1EPSPs. 3. With the use of stimulus intensities at or just
below threshold for evoking an action potential, complex synaptic
potentials consisting of EPSP-IPSP sequences were observed. Both
early, Cl(-)-dependent and late, K(+)-dependent IPSPs were reduced
by CNQX. This effect was reversible on washing. This disinhibition
could lead to enhanced excitability in the presence of CNQX. 4.
Iontophoretic application of quisqualate produced a membrane
depolarization with superimposed action potentials, whereas NMDA
depolarized the membrane potential and evoked bursts of action
potentials. At concentrations up to 5 microM, CNQX selectively
antagonized quisqualate responses. NMDA responses were reduced by
10 microM CNQX. D-Serine (0.5-2 mM), an agonist at the glycine
regulatory site on the NMDA receptor, reversed the CNQX depression
of NMDA responses.