Mossy fiber-CA3 synapses mediate homeostatic plasticity in mature hippocampal neurons.

Network activity homeostatically alters synaptic efficacy to constrain neuronal output. However, it is unclear how such compensatory adaptations coexist with synaptic information storage, especially in established networks. Here, we report that in mature hippocampal neurons in vitro, network activity preferentially regulated excitatory synapses within the proximal dendrites of CA3 neurons. These homeostatic synapses exhibited morphological, functional, and molecular signatures of the specialized contacts between mossy fibers of dentate granule cells and thorny excrescences (TEs) of CA3 pyramidal neurons. In vivo TEs were also selectively and bidirectionally altered by chronic activity changes. TE formation required presynaptic synaptoporin and was suppressed by the activity-inducible kinase, Plk2. These results implicate the mossy fiber-TE synapse as an independently tunable gain control locus that permits efficacious homeostatic adjustment of mossy fiber-CA3 synapses, while preserving synaptic weights that may encode information elsewhere within the mature hippocampal circuit.