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J Neurophysiol (March 1, 2003). 10.1152/jn.00644.2002
Submitted on Submitted 7 August 2002; accepted in final form 14 November
2002
Departments of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford, California 94305
Bandrowski, A. E.,
J. R. Huguenard, and
D. A. Prince.
Baseline Glutamate Levels Affect Group I and II mGluRs in Layer V
Pyramidal Neurons of Rat Sensorimotor Cortex. J. Neurophysiol. 89: 1308-1316, 2003. Possible
functional roles for glutamate that is detectable at low concentrations
in the extracellular space of intact brain and brain slices have not
been explored. To determine whether this endogenous glutamate acts on
metabotropic glutamate receptors (mGluRs), we obtained whole cell
recordings from layer V pyramidal neurons of rat sensorimotor cortical
slices. Blockade of mGluRs with
(+)-
-amino-4-carboxy--methyl-benzeacetic acid (MCPG, a general
mGluR antagonist) increased the mean amplitude of spontaneous excitatory postsynaptic currents (sEPSCs), an effect attributable to a
selective increase in the occurrence of large amplitude sEPSCs. 2S-2-amino-2-(1S,2S-2-carboxycyclopropyl-1-yl)-3-(xanth-9-yl)propanoic acid (LY341495, a group II antagonist) increased, but
R(
)-1-amino-2,3-dihydro-1H-indene-1,5-dicarboxylic acid
(AIDA) and (RS)-hexyl-HIBO (group I antagonists) decreased sEPSC
amplitude, and (R,S)--cyclopropyl-4-phosphonophenylglycine (CPPG, a
group III antagonist) did not change it. The change in sEPSCs elicited
by MCPG, AIDA, and LY341495 was absent in tetrodotoxin, suggesting that
it was action potential-dependent. The increase in sEPSCs persisted in
GABA receptor antagonists, indicating that it was not due to
effects on inhibitory interneurons. AIDA and (S)-3,5-dihydroxyphenylglycine (DHPG, a group I
agonist) elicited positive and negative shifts in holding current,
respectively. LY341495 and
(2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV, a
group II agonist) elicited negative and positive shifts in
holding current, respectively. The AIDA and LY341495 elicited currents
persisted in TTX. Finally, in current clamp, LY341495 depolarized cells
by ~2 mV and increased the number of action potentials to a given
depolarizing current pulse. Thus ambient levels of glutamate tonically
activate mGluRs and regulate cortical excitability.
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