Inhibitory interneurons of the hippocampus are a diverse population that play vital roles in regulating the activities of the more numerous and relatively homogenous groups of excitatory principal cells. In order to better understand the functions of different groups of interneurons, we used dual whole-cell patch-clamp recordings of interneurons from either stratum lucidum (SL) or stratum oriens (SO) and nearby CA3 pyramidal cells to investigate the morphologies and synaptic properties of IPSCs formed by these two groups of interneurons. SL interneurons have been implicated as mediators of feedforward inhibition between the dentate gyrus and CA3 pyramidal cells, while SO intemeurons mediate both feedback and feedforward inhibition within the highly interconnected CA3 pyramidal cell network. All recordings were performed in organotypic roller-tube cultures. Axodendritic synapses were formed by both interneuron groups on pyramidal cells. The kinetics of IPSCs were similar between the two groups, but the reliability of synaptic transmission of SL IPSCs was significantly lower than the virtually 100% reliability (non-existent failure rates) of SO IPSCs. In addition, SL intemeurons were less likely than SO intemeurons to innervate or to be innervated by nearby CA3 pyramidal cells. Biocytin staining revealed different morphologies between these interneuron groups, both being very similar to those found previously in acute slices. Paired-pulse stimulation at 100 ms interstimulus intervals produced similar paired-pulse depression in both interneuron synapses. However, during repetitive, high frequency stimulation (\u3e10 Hz for 500 ms) the two different synapses exhibited distinctly different forms of short-term plasticity: all SL interneurons displayed significant short-term facilitation, while, by contrast, SO interneuron synapses never displayed facilitation and often demonstrated significant depression. These results indicate that the pattern of innervation and synaptic properties of interneurons are different for interneurons in different hippocampal circuits. These results are relevant to the study of the role of hippocampal CA3 in memory functions in that these two interneuron populations may provide two different strategies for focusing mossy fiber inputs into activating specific networks within the C/A CA3 network. In addition, the short-term plasticities exhibited by these interneurons have implications for the development and propagation of seizures in the hippocampus
