Developmental changes in the expression of GABAA receptor subunits alpha1, alpha2, and alpha3 in the rat pre-Botzinger complex

Abstract

Previously, we reported that the pre-Bötzinger complex (PBC) exhibited a dramatic reduction in cytochrome oxidase activity at postnatal day (P) 12. This coincided in time with decreases in glutamate and NMDA receptor subunit 1 and increases in GABA, GABAB, glycine receptor, and glutamate receptor GluR2. To test our hypothesis that various alpha-subunits of GABAA receptors also undergo changes in their expression during postnatal development, as they do in other brain regions, we undertook an in-depth immunohistochemical study of GABAA receptor subunits alpha1, alpha2, and alpha3 in the PBC of P0 to P21 rats. We found that 1) GABAA alpha3-subunit was expressed at relatively high levels at P0, which then declined with age; 2) GABAA alpha1-subunit was expressed at relatively low levels at P0 but increased with age; 3) the developmental trends of subunits alpha1 and alpha3 intersected at P12; and 4) GABAA alpha2-subunit expression was moderate to light at P0 and remained quite constant during development, being lowest at P21. These findings suggest that the apparent switch in relative expressions of subunits alpha3 and alpha1 during development and the intersection of slopes around P12 may be associated with possible changes in GABAA receptor subtypes that would mediate different functional properties of GABA transmission, such as primarily a less efficient inhibitory transmission before P12 and a more mature inhibitory effect at P12 and thereafter, as suggested by the kinetics of distinct postsynaptic potentials. This mechanism may contribute partially to the dramatic reduction in cytochrome oxidase activity within the PBC at P12, as shown previously.