Differential long‐term depression in CA3 but not in dentate gyrus following low‐frequency stimulation of the medial perforant path

Abstract

Synaptic plasticity may depend not only on the afferent fibers but also on the recipient structure. The medial perforant path (MPP) from the entorhinalcortex projects to both the dentate gyrus (DG) and CA3, resulting in excitatory postsynaptic potentials (EPSPs) in both areas. In this study, we showed that long-term depression (LTD) following low-frequency stimulation of MPP was found only in CA3a, a CA3 subfield, but not in DG. Field potentials were recorded and current source density (CSD) analyzed in CA3a and DG following stimulation of MPP in urethane-anesthetized rats. MPP evoked a short-latency population spike (PS) and EPSP in CA3a, <2.5 ms delayed from the respective events in DG. A small electrolytic lesion of CA3a abolished the locally recorded PS in CA3a but did not affect the responses in the DG. Low-frequency stimulation of the MPP for 600 pulses at 5 Hz, but not at 1 Hz, resulted in LTD of up to 2 h in CA3a but not in DG. High-frequency stimulation (400 Hz bursts) of the MPP resulted in long-term potentiation (LTP) in both CA3a and DG. LTD at CA3a was blocked by a prior intracerebroventricular administration of an N-methyl-D-aspartate receptor (NMDAR) antagonist DL-2-amino-5-phosphonovaleric acid or a nonselective group I/II metabotropic glutamate receptor (mGluR) antagonist (RS)-α-methyl-4-carboxyphenylglycine. We conclude that an NMDAR and mGluR sensitive LTD is induced in CA3 but not in the DG following low-frequency MPP stimulation in vivo, and the bi-directional synaptic plasticity in CA3 may be responsible for its behavioral functions.