The entorhinal cortex plays a key role in processing memory information in the brain; superficial layers relay information to, and deep layers receive information from, the hippocampus. The cellular mechanisms of memory are thought to include a number that produce long-term potentiation (LTP) and depression (LTD) of synaptic strength. Our work presents evidence that LTP and LTD occur simultaneously at memory-relevant synapses. We report here that low frequency stimulation generates NMDA receptor-dependent LTD in Wistar rat superficial (layers II and III), and LTP in the deep entorhinal cortex layers (layers V and VI). LTP in deep layers is masked by simultaneously occurring voltage-gated calcium channel-dependent LTD. Our data support a novel mechanism for the sliding-threshold (BCM) model of synaptic plasticity: The sliding thresholds for induction of LTP and LTD in entorhinal cortex deep layers will be driven by the relative activation state of NMDA receptors and voltage-gated calcium channels. The co-expression of LTD and LTP at presynaptic sites in the entorhinal cortex deep layers reveals an intriguing mechanism for differential processing of synaptic information, which may underlie the vast dynamic capacity for information storage by this cortical structure.