Mossy Fiber-CA3 Synapses Mediate Homeostatic Plasticity in Mature Hippocampal Neurons

• Published in: Neuron (Cambridge, Mass.) Vol. 77; no. 1; pp. 99 - 114
• Main Authors: Lee, Kea Joo, Queenan, Bridget N., Rozeboom, Aaron M., Bellmore, Ryan, Lim, Seung T., Vicini, Stefano, Pak, Daniel T.S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.01.2013; Elsevier Limited
• Subjects: Adaptations; Animals; CA3 Region, Hippocampal - cytology; CA3 Region, Hippocampal - physiology; Cells, Cultured; Experiments; Hippocampus - cytology; Hippocampus - physiology; Homeostasis - physiology; Information storage; Morphology; Mossy Fibers, Hippocampal - physiology; Neuronal Plasticity - physiology; Neurons; Neurons - physiology; Rats; Software; Sucrose; Synapses - physiology
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2012.10.033

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. ► Mature hippocampal neurons have spatially segregated homeostatic plasticity in vitro ► Adaptation modulates mossy fiber synapses onto CA3 neuron thorny excrescences (TEs) ► Mossy fiber synaptoporin is necessary and sufficient for homeostatic plasticity ► Network activity and Plk2 selectively regulate TE structural plasticity in vivo Hippocampal networks homeostatically adjust to fluctuating activity while preserving previously encoded information. Lee et al. find that mossy fiber-CA3 synapses are the preferential locus of excitatory synaptic adaptation in mature hippocampal neurons, providing independently tunable gain control.