Is the place cell a supple engram?

This short note, which honors Nobelists O'Keefe and the Mosers, asks how the patterning of inputs to a single place cell regulates its firing. Because the combination of inputs to a single CA1 place cell is very large, the generally accepted view is rejected that inputs to a place cell are relatively restricted, near identical repetition upon re-presentation of the environment. The alternative proposed here is that when any 100 excitatory inputs are fired activating a subset combination, which is a large number, selected from the 30,000 synapses, this leads to CA1 cell firing. The selection of the combination of inputs is a very large number it nonetheless leads to the conclusion that even though the same cell dutifully fires when the animal is in an identical location, the inputs that fire the place cell are nonetheless obligatorily non-identical. This CA1 input combinatorial proposal may help us understand the physiological underpinnings of the memory mechanism arising from supple synapses (Routtenberg (2013), Hippocampus 23:202-206). (c) 2015 Wiley Periodicals, Inc.