Activity-mediated plasticity of GABA equilibrium potential in rat hippocampal CA1 neurons. Experimental neurology [Exp Neurol] Journal article

The equilibrium potential (E(GABA-PSC)) for gamma-aminobutyric acid (GABA) A receptor mediated inhibitory postsynaptic currents (PSCs) in hippocampal CA1 pyramidal neurons shifts when theta-burst stimulation (4 pulses at 100 Hz in each burst in a train consisting of 5 bursts with an inter-burst interval of 200 ms, the train repeated thrice at 30 s intervals) is applied to the input. E(GABA-PSC) is regulated by K(+)/Cl(-)co-transporter (KCC2). GABA(B) receptors are implicated in modulating KCC2 levels. In the current study, the involvement of KCC2 as well as GABA(B) receptors in theta-burst-mediated shifts in E(GABA-PSC,) were examined. Whole-cell patch recordings were made from hippocampal CA1 pyramidal neurons (from 9-12 day old rats), in a slice preparation. Glutamatergic excitatory postsynaptic currents were blocked with dl-2-Amino-5-phosphonovaleric acid (50 microM) and 6,7-dinitroquinoxaline-2,3-dione (20 microM). The PSC as well as the E(GABA-PSC) were stable when stimulated at 0.05 Hz. However, both changed following a 30 min stimulation at 0.5 or 1 Hz. Furosemide (500 microM) and KCC2 anti-sense in the recording pipette but not bumetanide (20 or 100 microM) or KCC2 sense, blocked the changes, suggesting KCC2 involvement. Theta-burst stimulation induced a negative shift in E(GABA-PSC,) which was prevented by KCC2 anti-sense; however, KCC2 sense had no effect. CGP55845 (2 microM), a GABA(B) antagonist, applied in the superfusing medium, or GDP-beta-S in the recording pipette, blocked the shift in E(GABA-PSC.) These results indicate that activity-mediated plasticity in E(GABA-PSC) occurs in hippocampal CA1 pyramidal neurons and theta-burst-induced negative shift in E(GABA-PSC) requires KCC2, GABA(B) receptors and G-protein activation.

Experimental neurology [Exp Neurol]