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Author Notes:

Email Address: pwenner@emory.edu

All authors conceived the experiments. M.-f.F. performed MEA recording, patch clamp and calcium imaging experiments.

J.P.N. designed and built the closed-loop optogenetic stimulation system. M.-f.F. and P.W. analysed the data.

M.-f.F. and P.W. wrote the paper, and all authors revised the manuscript.

We thank J.T. Shoemaker for performing tissue harvests, and M.C. LaPlaca for sharing tissue and providing a patch microscope.

We also thank the University of Pennsylvania Vector Core and K. Deiserroth for ChR2 constructs, C. Ramakrishnan for advice on AAV serotypes, A. Shaw for confocal imaging training, M.L. Mancini and W.A. Calhoun for help with calcium imaging setup.

We also thank S.L. Ritter for advice on glial immunocytochemistry, S.F. Traynelis for advice on AMPA receptor modulators and M.M. Rich for comments on the manuscript.

Subjects:

Research Funding:

NIH NINDS Grants R01NS065992 and R21NS084358 to P.W.,

NIH NINDS Grant R01NS079757 to S.M.P.

NSF GRFP Fellowship 09-603 to M.-f.F.

NSF GRFP Fellowship 08-593 to J.P.N.

NSF IGERT Fellowship DGE-0333411 to M.-f.F. and J.P.N

Emory NI SPINR Fellowship to M.-f.F.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • SPINAL-CORD
  • LONG-TERM
  • HOMEOSTATIC PLASTICITY
  • EXCITATORY SYNAPSES
  • QUANTAL AMPLITUDE
  • CORTICAL-NEURONS
  • NETWORKS
  • AMPA
  • SPASTICITY
  • RECEPTORS

Upward synaptic scaling is dependent on neurotransmission rather than spiking

Tools:

Journal Title:

Nature Communications

Volume:

Volume 6

Publisher:

, Pages 6339-6339

Type of Work:

Article | Final Publisher PDF

Abstract:

Homeostatic plasticity encompasses a set of mechanisms that are thought to stabilize firing rates in neural circuits. The most widely studied form of homeostatic plasticity is upward synaptic scaling (upscaling), characterized by a multiplicative increase in the strength of excitatory synaptic inputs to a neuron as a compensatory response to chronic reductions in firing rate. While reduced spiking is thought to trigger upscaling, an alternative possibility is that reduced glutamatergic transmission generates this plasticity directly. However, spiking and neurotransmission are tightly coupled, so it has been difficult to determine their independent roles in the scaling process. Here we combined chronic multielectrode recording, closed-loop optogenetic stimulation, and pharmacology to show that reduced glutamatergic transmission directly triggers cell-wide synaptic upscaling. This work highlights the importance of synaptic activity in initiating signalling cascades that mediate upscaling. Moreover, our findings challenge the prevailing view that upscaling functions to homeostatically stabilize firing rates.

Copyright information:

© 2015, Nature Publishing Group, a division of Macmillan Publishers Limited.

This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits distribution of derivative works, making multiple copies, distribution, public display, and publicly performance, provided the original work is properly cited. This license requires copyright and license notices be kept intact, credit be given to copyright holder and/or author.

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