Large-scale somatotopic refinement via functional synapse elimination in the sensory thalamus of developing mice.
Functional synapse elimination and strengthening are crucial developmental processes in the formation of precise neuronal circuits in the somatosensory system, but the underlying alterations in topographical organization are not yet fully understood. To address this issue, we generated transgenic mice in which afferent fibers originating from the whisker-related brain region, called the maxillary principal trigeminal nucleus (PrV2), were selectively visualized with genetically expressed fluorescent protein. We found that functional synapse elimination drove and established large-scale somatotopic refinement even after the thalamic barreloid architecture was formed. Before functional synapse elimination, the whisker sensory thalamus was innervated by afferent fibers not only from the PrV2, but also from the brainstem nuclei representing other body parts. Most notably, only afferent fibers from PrV2 onto a whisker sensory thalamic neuron selectively survived and were strengthened, whereas other afferent fibers were preferentially eliminated via their functional synapse elimination. This large-scale somatotopic refinement was at least partially dependent on somatosensory experience. These novel results uncovered a previously unrecognized role of developmental synapse elimination in the large-scale, instead of the fine-scale, somatotopic refinement even after the initial segregation of the barreloid map.
Department of Physiology, School of Medicine, Tokyo Women's Medical University, Tokyo 162-8666, Japan, Department of Physiological Sciences, School of Life Science, The Graduate University for Advanced Studies (SOKENDAI), Okazaki 444-8787, Japan, Department of Information Physiology, National Institute for Physiological Sciences, Okazaki 444-8787, Japan, Faculty of Advanced Techno-Surgery, Institute of Advanced Biomedical Engineering and Science, Graduate School of Medicine, Tokyo Women's Medical University, Tokyo 162-8666, Japan, Research and Development Division, Pioneer Corporation, Kanagawa 212-0031, Japan, Department of Neurosurgery, School of Medicine, Tokyo Women's Medical University, Tokyo 162-8666, Japan, and Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan.
Yuichi
Y
Takeuchi
Hidetsugu
H
Asano
Yoko
Y
Katayama
Yoshihiro
Y
Muragaki
Keiji
K
Imoto
Mariko
M
Miyata
D000818:Animals; D019706:Excitatory Postsynaptic Potentials; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D055495:Neurogenesis / Q000502:physiology*; D018408:Patch-Clamp Techniques; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D013788:Thalamus / Q000254:growth & development* / Q000648:ultrastructure*