Glycine receptors mediate excitation of subplate neurons in neonatal rat cerebral cortex.
The development of the cerebral cortex depends on genetic factors and early electrical activity patterns that form immature neuronal networks. Subplate neurons (SPn) are involved in the construction of thalamocortical innervation, generation of oscillatory network activity, and in the proper formation of the cortical columnar architecture. Because glycine receptors play an important role during early corticogenesis, we analyzed the functional consequences of glycine receptor activation in visually identified SPn in neocortical slices from postnatal day 0 (P0) to P4 rats using whole cell and perforated patch-clamp recordings. In all SPn the glycinergic agonists glycine, beta-alanine, and taurine induced dose-dependent inward currents with the affinity for glycine being higher than that for beta-alanine and taurine. Glycine-induced responses were blocked by the glycinergic antagonist strychnine, but were unaffected by either the GABAergic antagonist gabazine, the N-methyl-d-aspartate-receptor antagonist d-2-amino-5-phosphonopentanoic acid, or picrotoxin and cyanotriphenylborate, antagonists of alpha-homomeric and alpha1-subunit-containing glycine receptors, respectively. Under perforated-patch conditions, glycine induced membrane depolarizations that were sufficient to trigger action potentials (APs) in most cells. Furthermore, glycine and taurine decreased the injection currents as well as the synaptic stimulation strength required to elicit APs, indicating that glycine receptors have a consistent excitatory effect on SPn. Inhibition of taurine transport and application of hypoosmolar solutions induced strychnine-sensitive inward currents, suggesting that taurine can act as a possible endogenous agonist on SPn. In summary, these results demonstrate that SPn express glycine receptors that mediate robust excitatory membrane responses during early postnatal development.
Kilb
W
W
Institute of Physiology and Pathophysiology, Johannes Gutenberg University, Duesbergweg 6, 55128 Mainz, Germany. wkilb@uni-mainz.de
Hanganu
I L
IL
Okabe
A
A
Sava
B A
BA
Shimizu-Okabe
C
C
Fukuda
A
A
Luhmann
H J
HJ
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D005998:Glycine / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000145:classification* / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D018009:Receptors, Glycine / Q000502:physiology*; D013331:Strychnine / Q000494:pharmacology; D013654:Taurine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015091:beta-Alanine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018684:Glycine Agents; D018009:Receptors, Glycine; D015091:beta-Alanine; D013654:Taurine; C009558:taurocyamine; D005680:gamma-Aminobutyric Acid; D013331:Strychnine; D002118:Calcium; D005998:Glycine