Astrocytes regulate heterogeneity of presynaptic strengths in hippocampal networks

Dendrites are neuronal structures specialized for receiving and processing information through their many synaptic inputs. How input strengths are modified across dendrites in ways that are crucial for synaptic integration and plasticity remains unclear. We examined in single hippocampal neurons the...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 113; no. 19; pp. E2685 - E2694
Main Authors Letellier, Mathieu, Park, Yun Kyung, Chater, Thomas E., Chipman, Peter H., Gautam, Sunita Ghimire, Oshima-Takago, Tomoko, Goda, Yukiko
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 10.05.2016
SeriesPNAS Plus
Subjects
Action Potentials - physiology
Animals
Astrocytes - physiology
Biological Sciences
Calcium Signaling - physiology
Cell Communication - physiology
Dendrites
Heterogeneity
Hippocampus - physiology
Life Sciences
Membrane Potentials - physiology
Membranes
Mice
Mice, Inbred C57BL
Nerve Net - physiology
Neurobiology
Neurons
Neurons and Cognition
Neurosciences
Plasticity
PNAS Plus
Presynaptic Terminals - physiology
Proteins
Rats
Synaptic Transmission - physiology
synaptic strength
heterosynaptic plasticity
synapse heterogeneity
astrocyte
hippocampal neuron
Online AccessGet full text
ISSN0027-8424
1091-6490
1091-6490
DOI10.1073/pnas.1523717113

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Summary:Dendrites are neuronal structures specialized for receiving and processing information through their many synaptic inputs. How input strengths are modified across dendrites in ways that are crucial for synaptic integration and plasticity remains unclear. We examined in single hippocampal neurons the mechanism of heterosynaptic interactions and the heterogeneity of synaptic strengths of pyramidal cell inputs. Heterosynaptic presynaptic plasticity that counterbalances input strengths requires N-methyl-D-aspartate receptors (NMDARs) and astrocytes. Importantly, this mechanism is shared with the mechanism for maintaining highly heterogeneous basal presynaptic strengths, which requires astrocyte Ca2+ signaling involving NMDAR activation, astrocyte membrane depolarization, and L-type Ca2+ channels. Intracellular infusion of NMDARs or Ca2+-channel blockers into astrocytes, conditionally ablating the GluN1 NMDAR subunit, or optogenetically hyperpolarizing astrocytes with archaerhodopsin promotes homogenization of convergent presynaptic inputs. Our findings support the presence of an astrocyte-dependent cellular mechanism that enhances the heterogeneity of presynaptic strengths of convergent connections, which may help boost the computational power of dendrites.
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PMCID: PMC4868440
Author contributions: M.L. and Y.G. designed research; M.L., Y.K.P., T.E.C., P.H.C., S.G.G., and T.O.-T. performed research; M.L., Y.K.P., T.E.C., and P.H.C. analyzed data; and M.L. and Y.G. wrote the paper.
1Previous address: Medical Research Council Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London, London WC1E 6BT, United Kingdom.
2Present address: Interdisciplinary Institute for Neuroscience, University of Bordeaux, UMR 5297, 33077 Bordeaux, France.
4T.E.C. and P.H.C. contributed equally to this work.
Edited by Mu-ming Poo, Institute of Neuroscience and Key Laboratory of Primate Neurobiology, State Key Laboratory of Neuroscience, Chinese Academy of Sciences Center for Excellence in Brain Science, Shanghai Institutes for Biological Sciences, Shanghai, China, and approved March 28, 2016 (received for review December 1, 2015)
ISSN:0027-8424
1091-6490
1091-6490
DOI:10.1073/pnas.1523717113