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NMDA spikes enhance action potential generation during sensory input

Palmer, Lucy M. and Shai, Adam S. and Reeve, James E. and Anderson, Harry L. and Paulsen, Ole and Larkum, Matthew E. (2014) NMDA spikes enhance action potential generation during sensory input. Nature Neuroscience, 17 (3). pp. 383-390. ISSN 1097-6256.

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Recent evidence in vitro suggests that the tuft dendrites of pyramidal neurons are capable of evoking local NMDA receptor–dependent electrogenesis, so-called NMDA spikes. However, it has so far proved difficult to demonstrate their existence in vivo. Moreover, it is not clear whether NMDA spikes are relevant to the output of pyramidal neurons. We found that local NMDA spikes occurred in tuft dendrites of layer 2/3 pyramidal neurons both spontaneously and following sensory input, and had a large influence on the number of output action potentials. Using two-photon activation of an intracellular caged NMDA receptor antagonist (tc-MK801), we found that isolated NMDA spikes typically occurred in multiple branches simultaneously and that sensory stimulation substantially increased their probability. Our results demonstrate that NMDA receptors have a vital role in coupling the tuft region of the layer 2/3 pyramidal neuron to the cell body, enhancing the effectiveness of layer 1 input.

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Additional Information:© 2014 Nature America, Inc. Received 18 October 2013; accepted 20 December 2013; published online 2 February 2014. We thank F. Haiss and B. Weber for designing the custom-made two-photon microscope, and D. Langer and F. Helmchen for the imaging software Helioscan. We also thank S. Murphy and R. Min for their comments on the manuscript. We further acknowledge the GENIE Program and the Janelia Farm Research Campus for the use of GCaMP6. This work was supported by (NeuroChoice), Swiss National Science Foundation (31003A_130694), the Whitaker International Program and the DFG (EXC 257 NeuroCure). The authors declare no competing financial interests. Author Contributions: L.M.P. and M.E.L. designed, performed and analyzed the experiments. A.S.S. performed the computer simulations. J.E.R., H.L.A. and O.P. synthesized and provided the caged-MK801. L.M.P. and M.E.L. wrote the paper.
Funding AgencyGrant Number (NeuroChoice)UNSPECIFIED
Swiss National Science Foundation (SNSF)31003A_130694
Whitaker International ProgramUNSPECIFIED
Deutsche Forschungsgemeinschaft (DFG)Exc 257 NeuroCure
Issue or Number:3
Record Number:CaltechAUTHORS:20140210-130657179
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Official Citation:NMDA spikes enhance action potential generation during sensory input Lucy M Palmer, Adam S Shai, James E Reeve, Harry L Anderson, Ole Paulsen & Matthew E Larkum Published online: 02 February 2014 | doi:10.1038/nn.3646
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:43750
Deposited By: Ruth Sustaita
Deposited On:10 Feb 2014 21:43
Last Modified:03 Oct 2019 06:11

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