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

Nirnath Sah,Henriette Van Praag,Benjamin D Peterson,Susan T Lubejko,Carmen Vivar

doi:10.1038/s41598-017-11268-z

Abstract

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.

Highlights

Adult hippocampal neurogenesis is considered to play a role in memory function and mood[1,2,3]
The conventional view is that inputs to adult-born granule cells are initially GABAergic, followed by glutamatergic innervation around the second week of development[6,7,8, 10, 11]
This is consistent with the concept that adult neurogenesis recapitulates neuronal development during embryogenesis[7, 33]

Summary

Introduction

Adult hippocampal neurogenesis is considered to play a role in memory function and mood[1,2,3]. N-Methyl-D-aspartic acid receptors (NMDAR) are known to regulate prenatal neuronal development and connectivity[13, 14] Their role in the maturation and survival of adult-born neurons remains unclear. Application of a high concentration of NMDA in acute hippocampal slices resulted in dendritic beading, indicative of functional NMDAR, in some immature neurons at 7 dpi[17], providing support for the possibility that glutamatergic innervation may contribute to the initial wiring of new granule cells. We show that glutamatergic, but not GABAergic, inputs to adult-born granule cells are modified by running These findings add new dimensions to our understanding of the maturation and functional integration of newly born neurons in the adult brain

Methods

Results

Conclusion