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

Cereb Cortex. 2016 Jun;26(6):2715-27. doi: 10.1093/cercor/bhv127. Epub 2015 Jun 4.


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.

Keywords: GABA; granule cell; inhibition; mossy cell; optogenetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dentate Gyrus / physiology*
  • Excitatory Postsynaptic Potentials / physiology
  • Female
  • Immunohistochemistry
  • Inhibitory Postsynaptic Potentials / physiology
  • Interneurons / physiology*
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Inhibition / physiology
  • Optogenetics
  • Patch-Clamp Techniques
  • Perforant Pathway / physiology*
  • Receptors, Kainic Acid / genetics
  • Receptors, Kainic Acid / metabolism
  • Rhodopsin / genetics
  • Rhodopsin / metabolism
  • Tissue Culture Techniques


  • Grik4 protein, mouse
  • Receptors, Kainic Acid
  • Rhodopsin