Functional Specificity of Mossy Fiber Innervation of GABAergic Cells in the Hippocampus

Abstract

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.

Behavior-dependent specialization of identified hippocampal interneurons

“…Ivy cells are the quantitatively most abundant type of GABAergic interneuron in the CA1 area 25 . They provide widespread synaptic and extrasynaptic slow GABAergic input, as well as NPY and nitric oxide to pyramidal cell dendrites and Schaffer collateral/commissural terminals via their exceptionally dense axonal arborizations 25,26 and may mediate the activity-dependent regulation of neurogenesis 43 . The firing patterns identified here, are well suited to control homeostasis in the network.…”

“…1 and Table 1; primary antibodies are listed in Supplementary Table 1). Ivy cells 25,26 (n=3) had very fine and dense axons in the stratum-radiatum and stratum-oriens providing synaptic and extrasynaptic GABAergic input to pyramidal cell dendrites. Two out of three cells 27 were immunopositive for neuronal nitric oxide synthase (nNOS), and all tested cells expressed neuropeptide tyrosine (NPY) and a high level of neurokinin 1 receptor (NK1R), as well as the α1 and δ subunits of GABA A receptors in the somato-dendritic membrane ( Fig.…”

Target-Dependent Compartmentalization of the Corelease of Glutamate and GABA from the Mossy Fibers

“…The filopodial extensions and the small en passant varicosities seem to be selectively tuned to match different types of interneurons, which in turn innervate different parts of the pyramidal cell somatodendritic axis, or other interneurons (Acsády et al, 1998;Szabadics and Soltesz, 2009). According to this, MF GABAergic LTP on stratum lucidum interneurons would be participating in the refinement of neuronal connectivity while still controlling the overall excitability of pyramidal cells (RomoParra et al, 2008;Beltrán and Gutiérrez, 2012), rather than depressing the inhibitory network of CA3.…”

Temporal Lobe Epilepsy: Cell Death and Molecular Targets

“…In many cases, the hippocampal damage in TLE was accompanied by aberrant mossy fiber reorganization. Mossy fibers from the dentate granule cells, which normally innervate the hilar mossy cells and the CA3 pyramidal cells and interneurons, reorganize and project into the inner third of the molecular layer of the dentate gyrus (Sutula et al, 1989;Babb et al, 1991;Szabadics & Soltesz, 2009). The term "mesial temporal sclerosis" has been introduced to describe cellular damage in the hippocampus, amygdala and entorhinal cortex (De Lanerolle & Lee, 2005).…”