Activity-mediated plasticity of GABA equilibrium potential in rat hippocampal CA1 neurons

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