Activation of metabotropic glutamate receptors induces propagating network oscillations in the intact cerebral cortex of the newborn mouse.
Activation of metabotropic glutamate receptors (mGluRs) with (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) elicited in the frontal or occipital pole of the intact cerebral cortex preparation of the newborn mouse (P0-P3) a transient oscillatory field potential activity in the frequency range of 11-14Hz. These oscillations propagated over the whole cortical hemisphere and were blocked by tetrodotoxin, indicating that action potentials are required for the generation of this activity. Blockade of GABA-A receptors with gabazine did not influence the ACPD-induced network activity, but the glycine antagonist strychnine caused a significant decrease in the frequency, amplitude and duration of the oscillations. Bath application of kynurenic acid, the AMPA/kainate antagonist CNQX or the NMDA antagonist CPP induced a significant reduction in the response amplitude by 15-18%, indicating that ionotropic glutamate receptors are involved in this network activity. The selective mGluR-1a antagonist LY367385 and the mGluR-5 antagonist MPEP reversibly blocked the field potential oscillations, whereas the group II mGluR antagonist LY341495 did not block the activity. The network oscillations were also blocked by the gap junction inhibitors carbenoxolone and quinidine. These data indicate that ACPD-induced oscillatory network activity in the neonatal mouse cerebral cortex depends on action potential discharge, activation of group I mGluRs of type 1a and type 5 and intact gap junctional coupling. We suggest that this propagating large-scale network activity may play an important role in the functional formation of early neocortical circuits.
Wagner
Jan
J
Institute of Physiology and Pathophysiology, University of Mainz, Duesbergweg 6, D-55128 Mainz, Germany.
Luhmann
Heiko J
HJ
D000818:Animals; D000831:Animals, Newborn; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000033:anatomy & histology* / Q000502:physiology*; D018679:Cholinergic Agonists / Q000494:pharmacology; D004148:Dioxolanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009415:Nerve Net / Q000502:physiology*; D011687:Purines / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*
D018679:Cholinergic Agonists; D004148:Dioxolanes; D018691:Excitatory Amino Acid Antagonists; D011687:Purines; D018094:Receptors, Metabotropic Glutamate; C104068:4-(2-amino-6-chloro-9H-purin-9-yl)-1,3-dioxolane-2-methanol; D002217:Carbachol