6533b86dfe1ef96bd12cab37

RESEARCH PRODUCT

Glycine Receptors Mediate Excitation of Subplate Neurons in Neonatal Rat Cerebral Cortex

Heiko J. LuhmannWerner KilbChigusa Shimizu-okabeBogdan Aurel SavaAtsuo FukudaIleana L. HanganuAkihito Okabe

subject

Patch-Clamp TechniquesTaurinePhysiologyGlycineIn Vitro TechniquesBiologyMembrane PotentialsReceptors GlycineSubplatemedicineAnimalsDrug InteractionsGlycine receptorgamma-Aminobutyric AcidCerebral CortexNeuronsNeonatal ratDose-Response Relationship DrugGeneral NeuroscienceExcitatory Postsynaptic PotentialsDose-Response Relationship RadiationGlycine AgentsStrychnineElectric StimulationRatsmedicine.anatomical_structureAnimals NewbornCerebral cortexbeta-AlanineCalciumNeuroscience

description

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, β-alanine, and taurine induced dose-dependent inward currents with the affinity for glycine being higher than that for β-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 α-homomeric and α1-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.

https://doi.org/10.1152/jn.00657.2007