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, not much is known about action potential (AP) firing evoked by activation of GABAergic synapses. To identify newly generated young neurons in the adult brain, we used transgenic mice expressing the red fluorescent protein DsRed under the control of the doublecortin (DCX)-promoter. GABAergic synaptic currents and potentials were evoked in adult hippocampal brain slices in the presence of kynurenic acid. Perforated-patch recordings (gramicidin) revealed that the reversal potential of GABAergic synaptic currents is substantially more positive in DCX-expressing young neurons (-34.2±2.1 mV, n=4) as compared to mature granule cells (-71.9±2.9 mV, n=5). The synaptic currents were fully blocked by 10µM gabazine, showing that they are mediated by a GABA-A receptor mediated chloride conductance. Pairing of subthreshold somatic current injection with synaptic stimulation showed that GABAergic synapses facilitate AP generation within a conductance range of about 0.3 to 3.5 nS (n=4). Larger conductances, however, inhibited AP generation due to decrease in input resistance (130±30 M? versus 1.3±0.4 G? in control) indicating shunting inhibition. Thus, hippocampal interneurons can induce GABAergic excitation in newly generated young neurons of the adult brain. However, GABAergic excitation dynamically shifts towards shunting inhibition in an activity dependent manner.

Supported by Swiss National Science Foundation (SNF).