TY - JOUR T1 - Depolarizing Actions of GABA in Immature Neurons Depend Neither on Ketone Bodies Nor on Pyruvate JF - The Journal of Neuroscience JO - J. Neurosci. SP - 34 LP - 45 DO - 10.1523/JNEUROSCI.3314-10.2011 VL - 31 IS - 1 AU - Roman Tyzio AU - Camille Allene AU - Romain Nardou AU - Michel A. Picardo AU - Sumii Yamamoto AU - Sudhir Sivakumaran AU - Maddalena D. Caiati AU - Sylvain Rheims AU - Marat Minlebaev AU - Mathieu Milh AU - Pascal Ferré AU - Rustem Khazipov AU - Jean-Louis Romette AU - Jean Lorquin AU - Rosa Cossart AU - Ilgam Khalilov AU - Astrid Nehlig AU - Enrico Cherubini AU - Yehezkel Ben-Ari Y1 - 2011/01/05 UR - http://www.jneurosci.org/content/31/1/34.abstract N2 - GABA depolarizes immature neurons because of a high [Cl−]i and orchestrates giant depolarizing potential (GDP) generation. Zilberter and coworkers (Rheims et al., 2009; Holmgren et al., 2010) showed recently that the ketone body metabolite dl-3-hydroxybutyrate (dl-BHB) (4 mm), lactate (4 mm), or pyruvate (5 mm) shifted GABA actions to hyperpolarizing, suggesting that the depolarizing effects of GABA are attributable to inadequate energy supply when glucose is the sole energy source. We now report that, in rat pups (postnatal days 4–7), plasma d-BHB, lactate, and pyruvate levels are 0.9, 1.5, and 0.12 mm, respectively. Then, we show that dl-BHB (4 mm) and pyruvate (200 μm) do not affect (i) the driving force for GABAA receptor-mediated currents (DFGABA) in cell-attached single-channel recordings, (2) the resting membrane potential and reversal potential of synaptic GABAA receptor-mediated responses in perforated patch recordings, (3) the action potentials triggered by focal GABA applications, or (4) the GDPs determined with electrophysiological recordings and dynamic two-photon calcium imaging. Only very high nonphysiological concentrations of pyruvate (5 mm) reduced DFGABA and blocked GDPs. Therefore, dl-BHB does not alter GABA signals even at the high concentrations used by Zilberter and colleagues, whereas pyruvate requires exceedingly high nonphysiological concentrations to exert an effect. There is no need to alter conventional glucose enriched artificial CSF to investigate GABA signals in the developing brain. ER -