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Modulation of Inhibitory and Excitatory Fast Neurotransmission in the Rat Cns by Heavy Water (d 2 O) Running Title: Synaptic Transmission and Heavy Water

27 The effects of heavy water (deuterium oxide, D 2 O) on GABAergic and glutamatergic 28 spontaneous and evoked synaptic transmission were investigated in acute brain slice and 29 isolated 'synaptic bouton' preparations of rat hippocampal CA3 neurons. The substitution of 30 D 2 O for H 2 O reduced the frequency and amplitude of GABAergic spontaneous inhibitory 31 postsynaptic currents (sIPSCs) in a concentration-dependent manner, but had no effect on 32 glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs). In contrast, for evoked 33 synaptic responses in isolated neurons, the amplitude of both inhibitory and excitatory 34 postsynaptic currents (eIPSCs and eEPSCs) was decreased in a concentration-dependent 35 manner. This was associated with increases of synaptic failure rate (Rf) and paired-pulse ratio 36 (PPR). The effect was larger for eIPSCs as compared to eEPSCs. These results clearly 37 indicate that D 2 O acts differently on inhibitory and excitatory neurotransmitter release 38