The Suprapyramidal and Infrapyramidal Blades of the Dentate Gyrus Exhibit Different GluN Subunit Content and Dissimilar Frequency-Dependent Synaptic Plasticity In Vivo

Abstract

The entorhinal cortex sends afferent information to the hippocampus by means of the perforant path (PP). The PP input to the dentate gyrus (DG) terminates in the suprapyramidal (sDG) and infrapyramidal (iDG) blades. Different electrophysiological stimulation patterns of the PP can generate hippocampal synaptic plasticity. Whether frequency-dependent synaptic plasticity differs in the sDG and iDG is unclear. Here, we compared medial PP–DG responses in freely behaving adult rats and found that synaptic plasticity in the sDG is broadly frequency dependent, whereby long-term depression (LTD, > 24 h) is induced with stimulation at 1 Hz, short-term depression (< 2 h) is triggered by 5 or 10 Hz, 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 10 Hz stimulation, LTD induced by 1 Hz is weaker, LTP is not induced by 200 Hz and LTP induced by 400 Hz stimulation is significantly smaller in magnitude than LTP induced in sDG. Furthermore, the stimulus–response relationship of iDG is suppressed compared to sDG. These differences may arise from differences in granule cell properties, or the complement of NMDA receptors. 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 the middle molecular layer of iDG compared to sDG. Taken together, these data indicate that synaptic plasticity in the iDG is weaker, less persistent and less responsive to afferent frequencies than synaptic plasticity in sDG. Effects may be mediated by weaker NMDA receptor expression and differences in neuronal responses in iDG versus sDG. These characteristics may explain reported differences in experience-dependent information processing in the suprapyramidal and infrapyramidal blades of the DG.