Regulation of GABA Equilibrium Potential by mGluRs in Rat Hippocampal CA1 Neurons.(Author(s): Bo Yang 1 , Padmesh S. Rajput 2 , Ujendra Kumar 2 , Bhagavatula R. Sastry 1 Introduction [gamma]-aminobutyric acid )

• Published in: PloS one 2015-09, Vol.10 (9)
• Main Authors: Yang, Bo, Rajput, Padmesh S, Kumar, Ujendra, Sastry, Bhagavatula R
• Format: Article
• Language: English
• Subjects: GABA; Gene expression; Genetic aspects; Neurons; Physiological aspects
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0138215

The equilibrium potential for GABA-A receptor mediated currents (E.sub.GABA) in neonatal central neurons is set at a relatively depolarized level, which is suggested to be caused by a low expression of K.sup.+ /Cl.sup.- co-transporter (KCC2) but a relatively high expression of Na.sup.+ -K.sup.+ -Cl.sup.- cotransporter (NKCC1). Theta-burst stimulation (TBS) in stratum radiatum induces a negative shift in E.sub.GABA in juvenile hippocampal CA1 pyramidal neurons. In the current study, the effects of TBS on E.sub.GABA in neonatal and juvenile hippocampal CA1 neurons and the underlying mechanisms were examined. Metabotropic glutamate receptors (mGluRs) are suggested to modulate KCC2 and NKCC1 levels in cortical neurons. Therefore, the involvement of mGluRs in the regulation of KCC2 or NKCC1 activity, and thus E.sub.GABA, following TBS was also investigated. Whole-cell patch recordings were made from Wistar rat hippocampal CA1 pyramidal neurons, in a slice preparation. In neonates, TBS induces a positive shift in E.sub.GABA, which was prevented by NKCC1 antisense but not NKCC1 sense mRNA. (RS)-a-Methyl-4-carboxyphenylglycine (MCPG), a group I and II mGluR antagonist, blocked TBS-induced shifts in both juvenile and neonatal hippocampal neurons. While blockade of mGluR1 or mGluR5 alone could interfere with TBS-induced shifts in E.sub.GABA in neonates, only a combined blockade could do the same in juveniles. These results indicate that TBS induces a negative shift in E.sub.GABA in juvenile hippocampal neurons but a positive shift in neonatal hippocampal neurons via corresponding changes in KCC2 and NKCC1 expressions, respectively. mGluR activation seems to be necessary for both shifts to occur while the specific receptor subtype involved seems to vary.