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

Abstract

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.

5-HT3AReceptor-Bearing White Matter Interstitial GABAergic Interneurons Are Functionally Integrated into Cortical and Subcortical Networks

“…Most subplate cells apoptose perinatally and postnatally, but some persist into adulthood as a thin layer (layer VIb) between cortex and white matter (Kostovic and Rakic, 1980;Al-Ghoul and Miller, 1989;Chun and Shatz, 1989;Kostovic and Rakic, 1990;Allendoerfer and Shatz, 1994). Differences in perikaryon location, anatomy, and physiology of 5-HT 3A -EGFP-positive WMICs and layer VIb neurons (Valverde and Facal-Valverde, 1988;Friauf et al, 1990;Luhmann et al, 2000;Hanganu et al, 2001Hanganu et al, , 2002Hanganu et al, , 2009Torres-Reveron and Friedlander, 2007;Kilb et al, 2008;Zhao et al, 2009) support the notion that in rodents GABAergic WMICs descend from lower intermediate zone GABAergic cells and not from subplate neurons (DeDiego et al, 1994;Tamamaki et al, 1997Tamamaki et al, , 2003aTamamaki et al, , 2003bOkhotin and Kalinichenko, 2003). In summary, we described here 5-HT 3A receptor-bearing GABAergic WMICs that resemble cortical interneurons based on morphology, interneuron marker expression, and electrophysiological features.…”

Taurine Inhibits K+-Cl− Cotransporter KCC2 to Regulate Embryonic Cl− Homeostasis via With-no-lysine (WNK) Protein Kinase Signaling Pathway

“…Several reports have shown that these early generated neurons in the marginal zone and subplate are activated by GABA and glycine (82)(83)(84)(85). These early generated neurons can express KCC2 as early as the embryonic and neonatal stages (86).…”

Cation-chloride cotransporters in neuronal development, plasticity and disease

“…Strongly depolarizing GABAergic synaptic responses can be functionally excitatory, and they are termed ‘GABA PSPs’. Such responses are based on a high [Cl − ] i , and they are mainly seen in immature or diseased neurons 40,48,165–168 .…”