Functional specificity of mossy fiber innervation of GABAergic cells in the hippocampus

One million mossy fibers in the rat provide individually sparse but functionally important synaptic connections between the dentate gyrus and hippocampus. Although the majority of mossy fiber targets are GABAergic cells, the functional organization of the feedforward GABAergic machinery modulating the interactions of granule cells and CA3 pyramidal cells are not yet understood. We used mossy fiber bouton to GABA neuron paired recordings in the CA3 to demonstrate that mossy fibers provide cell type-specific innervation to distinct GABAergic neurons with specialized intra- and extrahippocampal outputs. Our results show that mossy fibers contact the perisomatically projecting fast-spiking and regular-spiking basket cells, in addition to the dendritically projecting ivy cells, and the septum-projecting spiny stratum lucidum cells. Monosynaptic mossy fiber inputs to fast-spiking basket cells and spiny stratum lucidum cells were found to be numerous, but they were small in amplitude and displayed low transmission probabilities. In contrast, regular-spiking basket cells and ivy cells were less likely to be innervated by mossy fibers, but the amplitudes of mossy fiber EPSCs were large and the transmission probabilities were high. The dependence of the numbers and strengths of the mossy fiber inputs to CA3 GABAergic cells on the postsynaptic cell type was correlated with the frequency of the background synaptic events, so that cells with weak but numerous mossy fiber inputs received high rates of spontaneous synaptic events. Together, these results reveal the diverse components and high degree of functional specificity of the GABAergic cellular machinery underlying the dentate gyrus-CA3 interface.