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Author Notes:

Correspondence to: S.P. Yu, 101 Woodruff Circle; Suite 620, Emory University School of Medicine, Atlanta, GA 30322, USA. spyu@emory.edu

Conflict of Interests: The authors declare no conflict of interests related to this research.

Subjects:

Research Funding:

This study was supported by an American Heart Association (AHA) Postdoctoral Fellowship 12POST12080252 (MS), NIH grants NS0458710 (SPY), NS085568 (LW/SPY), NS091585 (LW) and a VA Merit grant RX000666 (SPY).

It was also supported by the O. Wayne Rollins Endowed Chair fund to SPY and the John E. Steinhaus Endowed Chair fund to LW.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • SVZ neurogenesis
  • Striatum stimulation
  • Optogenetics
  • Glutamatergic neurons
  • Ischemic stroke
  • Semi-phasic synaptic regulation
  • Functional recovery
  • FOCAL CEREBRAL-ISCHEMIA
  • ADULT MAMMALIAN BRAIN
  • MESENCHYMAL STEM-CELLS
  • ADHESIVE REMOVAL TEST
  • SPONTANEOUS REPERFUSION
  • IN-VIVO
  • ARTERY OCCLUSION
  • TRANSGENIC MICE
  • SYNAPSIN-I
  • MIGRATION

Optogenetic stimulation of glutamatergic neuronal activity in the striatum enhances neurogenesis in the subventricular zone of normal and stroke mice

Tools:

Journal Title:

Neurobiology of Disease

Volume:

Volume 98

Publisher:

, Pages 9-24

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Neurogenesis in the subventricular zone (SVZ) of the adult brain may contribute to tissue repair after brain injuries. Whether SVZ neurogenesis can be upregulated by specific neuronal activity in vivo and promote functional recovery after stroke is largely unknown. Using the spatial and cell type specific optogenetic technique combined with multiple approaches of in vitro, ex vivo and in vivo examinations, we tested the hypothesis that glutamatergic activation in the striatum could upregulate SVZ neurogenesis in the normal and ischemic brain. In transgenic mice expressing the light-gated channelrhodopsin-2 (ChR2) channel in glutamatergic neurons, optogenetic stimulation of the glutamatergic activity in the striatum triggered glutamate release into SVZ region, evoked membrane currents, Ca 2 + influx and increased proliferation of SVZ neuroblasts, mediated by AMPA receptor activation. In ChR2 transgenic mice subjected to focal ischemic stroke, optogenetic stimuli to the striatum started 5 days after stroke for 8 days not only promoted cell proliferation but also the migration of SVZ neuroblasts into the peri-infarct cortex with increased neuronal differentiation and improved long-term functional recovery. These data provide the first morphological and functional evidence showing a unique striatum-SVZ neuronal regulation via a semi-phasic synaptic mechanism that can boost neurogenic cascades and stroke recovery. The benefits from stimulating endogenous glutamatergic activity suggest a novel regenerative strategy after ischemic stroke and other brain injuries.

Copyright information:

© 2016 Elsevier Inc.

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