Experimental and modeling studies of the contribution of NMDA receptor-channels to the expression of long-term potentiation

We Investigated the contribution of NMDA receptor-channels (NMDARs) to the expression of long-term potentiation (LTP) using electrophysiological and modeling methods. Intracellular recordings were obtained from hippocampal dentate gyrus (DG) granule cells. Perforant path afferents were stimulated with short bursts of pulses at 40 Hz, instead of the traditional protocol of a single stimulus at less than 0.1 Hz. The synaptic summation provided by the "burst" protocol enabled us to measure the NMDAR-mediated component of synaptic responses in the presence of physiological concentrations of Mg²⁺. We tested the hypothesis that NMDARs undergo LTP by comparing the NMDA/AMPA ratio of synaptic responses of control and LTP slices. An increase in the ratio was observed in the LTP group strongly suggesting potentiation of the NMDARs. In order to infer changes in synaptic conductances based on EPSPs recorded at the soma, we constructed a compartmental model of a granule cell. The effect of changes in AMPAR synaptic conductances, and of changes in the distribution of activated synapses on the NMDA/AMPA ratio was studied with computer simulations. Results confirmed that NMDARs are potentiated following LTP induction, and contribute significantly to the expression of LTP.