Preferential frequency-dependent induction of synaptic depression by the lateral perforant path and of synaptic potentiation by the medial perforant path inputs to the dentate gyrus

Abstract

The encoding of spatial representations is enabled by synaptic plasticity. The entorhinal cortex sends information to the hippocampus via the lateral (LPP) and medial perforant (MPP) paths that transfer egocentric item-related and allocentric spatial information, respectively. To what extent LPP and MPP information-relay results in different homosynaptic synaptic plasticity responses is unclear. We examined the frequency dependency (at 1, 5, 10, 50, 100, 200 Hz) of long-term potentiation (LTP) and long-term depression (LTD) at MPP and LPP synapses in the dentate gyrus (DG) of freely behaving adult rats. We report that whereas the MPP–DG synapses exhibit a predisposition toward the expression of LTP, LPP–DG synapses prefer to express synaptic depression. The divergence of synaptic plasticity responses is most prominent at afferent frequencies of 5, 100, Hz and 200 Hz. Priming with 10 or 50 Hz significantly modified the subsequent plasticity response in a frequency-dependent manner, but failed to change the preferred direction of change in synaptic strength of MPP and LPP synapses. Evaluation of the expression of GluN1, GluN2A, or GluN2B subunits of the NMDA receptor revealed equivalent expression in the outer and middle thirds of the molecular layer where LPP and MPP inputs convene, respectively, thus excluding NMDA receptors as a substrate for the frequency-dependent differences in bidirectional plasticity. These findings demonstrate that the LPP and MPP inputs to the DG enable differentiated and distinct forms of synaptic plasticity in response to the same afferent frequencies. Effects are extremely robust and resilient to metaplastic priming. These properties may support the functional differentiation of allocentric and item information provided to the DG by the MPP and LPP, respectively, that has been proposed by others. We propose that allocentric spatial information, conveyed by the MPP is encoded through hippocampal LTP in a designated synaptic network. This network is refined and optimized to include egocentric contextual information through LTD triggered by LPP inputs.