Running reorganizes the circuitry of one-week-old adult-born hippocampal neurons

• Published in: Scientific reports Vol. 7; no. 1; pp. 10903 - 15
• Main Authors: Sah, Nirnath, Peterson, Benjamin D, Lubejko, Susan T, Vivar, Carmen, van Praag, Henriette
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 07.09.2017; Nature Publishing Group UK
• Subjects: Action Potentials; Adult; Animals; Cell number; Cytology; Embryogenesis; Functional plasticity; Glutamatergic transmission; Granule cells; Hippocampal plasticity; Hippocampus; Hippocampus - physiology; Humans; Innervation; Interneurons; Mice, Inbred C57BL; N-Methyl-D-aspartic acid; Nerve Net - physiology; Neurogenesis; Neurons - physiology; Patch-Clamp Techniques; Pyramidal cells; Rodents; Running; Structure-function relationships; Wheel running; γ-Aminobutyric acid
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-11268-z

Adult hippocampal neurogenesis is an important form of structural and functional plasticity in the mature mammalian brain. The existing consensus is that GABA regulates the initial integration of adult-born neurons, similar to neuronal development during embryogenesis. Surprisingly, virus-based anatomical tracing revealed that very young, one-week-old, new granule cells in male C57Bl/6 mice receive input not only from GABAergic interneurons, but also from multiple glutamatergic cell types, including mature dentate granule cells, area CA1-3 pyramidal cells and mossy cells. Consistently, patch-clamp recordings from retrovirally labeled new granule cells at 7-8 days post retroviral injection (dpi) show that these cells respond to NMDA application with tonic currents, and that both electrical and optogenetic stimulation can evoke NMDA-mediated synaptic responses. Furthermore, new dentate granule cell number, morphology and excitatory synaptic inputs at 7 dpi are modified by voluntary wheel running. Overall, glutamatergic and GABAergic innervation of newly born neurons in the adult hippocampus develops concurrently, and excitatory input is reorganized by exercise.