Differential Recruitment of Dentate Gyrus Interneuron Types by Commissural Versus Perforant Pathways

Abstract

Gamma-aminobutyric acidergic (GABAergic) interneurons (INs) in the dentate gyrus (DG) provide inhibitory control to granule cell (GC) activity and thus gate incoming signals to the hippocampus. However, how various IN subtypes inhibit GCs in response to different excitatory input pathways remains mostly unknown. By using electrophysiology and optogenetics, we investigated neurotransmission of the hilar commissural pathway (COM) and the medial perforant path (MPP) to the DG in acutely prepared mouse slices. We found that the short-term dynamics of excitatory COM-GC and MPP-GC synapses was similar, but that the dynamics of COM- and MPP-mediated inhibition measured in GCs was remarkably different, during theta-frequency stimulation. This resulted in the increased inhibition-excitation (I/E) ratios in single GCs for COM stimulation, but decreased I/E ratios for MPP stimulation. Further analysis of pathway-specific responses in identified INs revealed that basket cell-like INs, total molecular layer- and molecular layer-like cells, received greater excitation and were more reliably recruited by the COM than by the MPP inputs. In contrast, hilar perforant path-associated and hilar commissural-associational pathway-related-like cells were minimally activated by both inputs. These results demonstrate that distinct IN subtypes are preferentially recruited by different inputs to the DG, and reveal their relative contributions in COM-mediated feedforward inhibition.

Mossy Cells Control Adult Neural Stem Cell Quiescence and Maintenance through a Dynamic Balance between Direct and Indirect Pathways

“…Interestingly, CNO-induced responses in dentate GABA neurons were highly heterogeneous (Fig. 3B-D), consistent with the recent finding that the MC commissural pathway preferentially recruits several subsets of dentate GABA interneurons (Hsu et al, 2016). Dentate PV interneurons can functionally interact with and regulate rNSCs (Song et al, 2012), and our Ca2+ imaging showed 32% of the responding cells were from the SGZ where PV basket cells reside (Fig.…”

“…1A-B). Since GCs and pyramidal cells do not project to the contralateral DG (Hsu et al, 2016), we limited our structural and functional analyses to the contralateral side for specificity. Within the hilus, injection of AAV-CaMKII-mCherry labeled ~82% of GluR2/3+ cells (specific marker for MCs) and ~94% of AAV-CaMKII-mCherry labeled cells were positive for GluR2/3 (Fig.…”

“…These data provide high-resolution structural support for a direct glutamatergic MC-rNSC pathway. MCs also interact with several distinct types of dentate GABAergic interneurons (Hsu et al, 2016; Scharfman, 1995). It is possible that there is a substantial disynaptic GABAergic pathway onto the rNSCs.…”

“…Recent studies showed that optogenetic activation of MC contralateral projections exerted a net inhibitory effect on GCs through disynaptic inhibition by preferentially recruiting basket cells (Hsu et al, 2016). Furthermore, MC loss caused a disinhibition and transient hyperexcitability of GCs (Jinde et al, 2012).…”

Subcellular Patch-clamp Recordings from the Somatodendritic Domain of Nigral Dopamine Neurons

“…First, as DIC prisms are not required, the IR-DGC image can be overlaid with a fluorescence image 49,52,53,76 . Second, DGC can be combined with photostimulation and optogenetics 77 .…”