Postnatal development of glycine receptor subunits α1, α2, α3, and β immunoreactivity in multiple brain stem respiratory-related nuclear groups of the rat.
The respiratory system is immature at birth and significant development occurs postnatally. A critical period of respiratory development occurs in rats around postnatal days 12-13, when enhanced inhibition dominates over suppressed excitation. The mechanisms underlying the heightened inhibition are not fully understood. The present study tested our hypothesis that the inhibition is marked by a switch in glycine receptor subunits from neonatal to adult form around the critical period. An in-depth immunohistochemical and single neuron optical densitometric study was undertaken on four respiratory-related nuclear groups (the pre-Bötzinger complex, nucleus ambiguus, hypoglossal nucleus, and ventrolateral subnucleus of solitary tract nucleus), and a non-respiratory cuneate nucleus in P2-21 rats. Our data revealed that in the respiratory-related nuclear groups: (1) the expressions of GlyRα2 and GlyRα3 were relatively high at P2, but declined after 1-1½ weeks to their lowest levels at P21; (2) the expression of GlyRα1 increased with age and reached significance at P12; and (3) the expression of GlyRβ rose from P2 to P12 followed by a slight decline until P21. No distinct increase in GlyRα1 at P12 was noted in the cuneate nucleus. Thus, there is a switch in dominance of expression from neonatal GlyRα2/α3 to the adult GlyRα1 and a heightened expression of GlyRα1 around the critical period in all respiratory-related nuclear groups, thereby supporting enhanced inhibition at that time. The rise in the expression of GlyRβ around P12 indicates that it plays an important role in forming the mature heteropentameric glycine receptors in these brain stem nuclear groups.
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Qiuli
Q
Liu
Margaret T T
MT
Wong-Riley
D000818:Animals; D001933:Brain Stem / Q000737:chemistry* / Q000166:cytology / Q000254:growth & development*; D005260:Female; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine / Q000032:analysis* / Q000276:immunology; D012143:Respiratory Physiological Phenomena
C501174:Glra2 protein, rat; C491948:Glrb protein, rat; D018009:Receptors, Glycine; C113965:glycine receptor alpha3 subunit
5-HT; ANOVA; APB; Amb; BDNF; CN; CNS; Critical period; Cuneate nucleus; GABA; GlyR; Hypoglossal nucleus; IPSC; IgG-HRP; K(+)–Cl(−) co-transporter 2; KCC2; N-methyl-d-aspartate receptor; NK1R; NKCC1; NMDAR; NTS(VL); Na(+)–K(+)–2Cl(−) co-transporter 1; Nucleus ambiguus; P; PBC; PBS; Pre-Bötzinger complex; TrkB; Ventrolateral subnucleus of solitary tract nucleus; XII; ammonium phosphate buffer; analysis of variance; brain-derived neurotrophic factor; central nervous system; cuneate nucleus; gamma aminobutyric acid; glycine receptor; hypoglossal nucleus; immunoglobulin conjugated to horseradish peroxidase; immunoreactive; inhibitory postsynaptic currents; ir; neurokinin 1 receptor; nucleus ambiguus; phosphate buffered saline; postnatal day; pre-Bötzinger complex; serotonin; tyrosine protein kinase B; ventrolateral subnucleus of the solitary tract nucleus