The suprapyramidal and infrapyramidal blades of the dentate gyrus exhibit different GluN subunit content and dissimilar frequency-dependent synaptic plasticity in vivo

The entorhinal cortex sends afferent information to the hippocampus by means of the perforant path(PP), whereby the medial PP (MPP) is believed to convey information about spatial context and the lateral PP (LPP) may convey information about item identity. This information is encoded by means of synaptic plasticity. The PP input to the dentate gyrus(DG) terminates in the suprapyramidal (upper/inner) and infrapyramidal (lower/outer) blades. To what extent frequency-dependent synaptic plasticity in these blades differs is unclear. Here, we compared MPP-DG responses in the supra- (sDG) and infrapyramidal blades (iDG) of freely behaving adult rats and found that synaptic plasticity in the sDG is broadly frequency-dependent whereby long-term depression (LTD, >24h) is induced with stimulation at 1Hz, short-term depression (<2h) is triggered by 5 or 10Hz and long-term potentiation (LTP) of increasing magnitudes is induced by 200 and 400 Hz stimulation, respectively. By contrast, although the iDG expresses STD following 5 or 10Hz stimulation, LTD induced by 1Hz is weaker, LTP is not induced by 200Hz and LTP induced by 400Hz stimulation is significantly smaller in magnitude and is less persistent (<4h) compared to LTP in sDG. Furthermore, the stimulus-response relationship of the iDG is suppressed compared to sDG. Patch clamp recordings, in vitro, revealed reduced firing frequencies in response to high currents, and different action potential thresholds in iDG compared to sDG. Assessment of the expression of GluN subunits revealed significantly lower expression levels of GluN1, GluN2A and GluN2B in iDG compared to sDG. Taken together, these data indicate that synaptic plasticity in the infrapyramidal blade of the dentate gyrus is weaker, less persistent and less responsive to afferent frequencies than synaptic plasticity in sDG. Effects may be mediated by weaker NMDA receptor expression in iDG. These characteristics may explain reported differences in experience-dependent information processing in sDG versus iDG. ### Competing Interest Statement The authors have declared no competing interest.