Long-term enhancement of excitatory synaptic inputs to layer V parahippocampal neurons by low frequency stimulation in rat brain slices

Excitatory inputs to layer V neurons of the parasubiculum and medial entorhinal cortex were examined in rat brain slices with intracellular and field potential recordings. Single extracellular stimuli to layer V evoked subthreshold excitatory postsynaptic potentials (EPSPs) or a long duration (> 100 ms) depolarization that sustained high frequency firing. Repetitive stimulation at low frequencies (from 1/10 s to 1/min) induced stable long-lasting decreases in the threshold for firing in individual cells or population events, and also induced stable long-lasting increases in evoked intracellular or field response amplitudes. More stimuli were required to produce the equivalent changes in threshold and amplitude in the presence of MCPG (200 μM). Smaller changes in amplitude, but equivalent changes in threshold were elicited in the presence of CPP (10 μM), or CPPG (20 μM). No changes in threshold or amplitude were detected in the presence of CNQX (10 μM), even when used in combination with picrotoxin (100 μM). EPSP facilitation was enhanced greatly by firing in postsynaptic cells. It is suggested that stable changes in excitatory inputs to layer V parahippocampal neurons involve the activation of NMDA and metabotropic glutamate receptors, but requires AMPA receptor activation and postsynaptic cell firing.