Neuronal activities in superficial (II and III) and deep (V and VI) layers of the entorhinal cortex (EC) are preferentially modulated by theta and sharp wave (SPW) EEG, respectively. We investigated the possibility that distinct EEG patterns represent optimal stimulus patterns for induction of long-term potentiation (LTP) in different layers of the EC. We examined effects of three different stimulation patterns on LTP induction in layers I, II-III, and V of medial EC slices of the rat. The stimulation patterns we used were a single, long high-frequency train (1 sec at 100 Hz, repeated 3x), theta burst stimulation [TBS; 10 bursts (four pulses, 100 Hz) at 5 Hz, repeated 3x], and SPW-like burst stimulation [ SPWBS; three bursts (20 pulses, 200 Hz) at 2 Hz, repeated 6x]. Similar degrees of LTP were induced by the three stimulation patterns in layer I. In layers II--III and layer V, however, the largest degrees of LTP were induced by TBS and SPWBS, respectively. These results suggest that burst stimulation constructed to mimic naturally occurring patterns of neuronal activity in the corresponding layer is optimal for LTP induction in layers II-III and layer V of the EC. The differences may play important roles in shaping hippocampal-neocortical interactions in encoding and retrieval of memory.