Effects of mossy fiber stimulation on hippocampal CA3 neurons in behaving mice

Abstract

Strong hippocampal mossy fiber synapses are thought to function as detonators, imposing ‘teaching’ signals onto CA3 neurons during new memory formation. However, such strong inputs may disrupt previously formed neural representations. I found that optogenetic stimulation of mossy fibers can drive CA3 neuronal firing in freely-moving mice, but their effects are overall inhibitory and transient. Spatially restricted mossy fiber stimulation emulating dentate place cell firing, either congruent or incongruent with CA3 place fields, was more likely to suppress than enhance CA3 neuronal activity. Also, changes in spatial firing induced by optogenetic stimulation reverted immediately upon stimulation termination, leaving CA3 place fields unaltered. My results argue against the standard view that mossy fibers convey teaching signals, and show the robustness of established CA3 spatial representations.