Newly generated, young hippocampal granule cells receive GABAergic synaptic inputs, which were shown to be important for their development and functional maturation. Although it is believed that depolarizing GABAergic synaptic inputs may be excitatory in young granule cells, it is unknown whether action potentials (APs) will be generated or shunting inhibition predominates. To investigate GABAergic excitation and inhibition, synaptic currents and potentials were evoked with extracellular stimulation in the granule cell layer in the presence of CNQX and AP-5. Patch pipettes were filled with a solution containing 25mM KCl mimicking the elevated intracellular Cl^- concentration as previously estimated for young granule cells. At a resting membrane potential of -80 mV GABAergic depolarizing potentials could be evoked, which were fully blocked by 10 mM gabazine. Increasing stimulation strength increased the initial PSP slope and evoked action potentials within an initial slope range of ~1–2 V/s. At stronger stimulation intensities AP generation was inhibited. Pairing of somatic current injection with synaptic stimulation showed that GABAergic synapses facilitate AP generation within a conductance range of 0.6±0.1 to 5.7±0.2 nS (n=9). Larger conductances interfered with AP generation due to strong decrease in input resistance (74±6 M[ohm] versus 2.1±0.4 G[ohm] in control) and decrease in membrane time constant (2.2±0.5 ms versus 138.1±17.9 ms) indicating shunting inhibition. Thus, hippocampal interneurons can induce GABAergic excitation in newly generated young granule cells which dynamically shifts towards shunting inhibition in an activity dependent manner.

(Supported by DFG Bi 624/2 and Swiss National Science Foundation).