A whole-cell patch-clamp study was carried out in slices obtained from young rat brain to elucidate the roles of somatostatin (SS) in the modulation of synaptic transmission onto cholinergic neurons in the basal forebrain (BF), a region that contains cholinergic and GABAergic corticopetal neurons and SS-containing local circuit neurons. Cholinergic neurons within the BF were identified by in vivo prelabeling with Cy3- 192IgG. Since in many cases SS is contained in GABAergic neurons in the CNS, we investigated whether exogenously applied SS can influence GABAergic transmission onto cholinergic neurons. Bath application of SS (1 µ) reduced the amplitude of the evoked GABAergic IPSCs in cholinergic neurons. SS also reduced the frequency of miniature IPSCs (mIPSCs) without affecting their amplitude distribution. SS-induced effect on the mIPSC frequency was significantly larger in the solution containing 7.2 mM Ca²⁺ than in the standard (2.4 mM Ca²⁺) external solution. Similar effects were observed in the case of non-NMDA glutamatergic EPSCs. SS inhibited the amplitude of evoked EPSCs, and reduced the frequency of miniature EPSCs dependent on the external Ca²⁺ concentration with no effect on their amplitude distribution. Pharmacological analyses using SS receptor subtype-specific drugs suggest that SS-induced action of the IPSCs is mediated mostly by sst₂ subtype, whereas sst subtypes mediating SS-induced inhibition of EPSCs are mainly sst₁ or sst4. These findings suggest that SS presynaptically inhibits both GABA and glutamate release onto BF cholinergic neurons in a Ca²⁺-dependent way, and that SS-induced effects on IPSCs and EPSCs are mediated different sst subtypes.