@article{4e35eea07c4a4c098f501f377ea0a1c8,
title = "Astrocyte-Mediated Distributed Plasticity at Hypothalamic Glutamate Synapses",
abstract = "Afferent activity can induce fast, feed-forward changes in synaptic efficacy that are synapse specific. Using combined electrophysiology, caged molecule photolysis, and Ca2+ imaging, we describe a plasticity in which the recruitment of astrocytes in response to afferent activity causes a fast and feed-forward, yet distributed increase in the amplitude of quantal synaptic currents at multiple glutamate synapses on magnocellular neurosecretory cells in the hypothalamic paraventricular nucleus. The plasticity is largely multiplicative, consistent with a proportional increase or {"}scaling{"} in the strength of all synapses on the neuron. This effect requires a metabotropic glutamate receptor-mediated rise in Ca2+ in the astrocyte processes surrounding the neuron and the release of the gliotransmitter ATP, which acts on postsynaptic purinergic receptors. These data provide evidence for a form of distributed synaptic plasticity that is feed-forward, expressed quickly, and mediated by the synaptic activation of neighboring astrocytes.",
keywords = "CELLBIO, MOLNEURO, SIGNALING",
author = "Gordon, \{Grant R.J.\} and Iremonger, \{Karl J.\} and Srinivas Kantevari and Ellis-Davies, \{Graham C.R.\} and MacVicar, \{Brian A.\} and Bains, \{Jaideep S.\}",
note = "Funding Information: We thank members of the lab and Dr. Quentin Pittman for comments on an earlier version of the manuscript, Dr. D.V. Baimoukhametova who participated in pilot experiments, and Ms C. Sank for technical assistance. During the course of this work, G.R.J.G. was supported by the Alberta Heritage Foundation for Medical Research (AHFMR), the Heart and Stroke Foundation of Canada (HSFC), the Michael Smith Foundation for Health Research (MSFHR), and the Natural Sciences and Engineering Council of Canada (NSERC). K.J.I. is supported by studentships from AHFMR and HSFC. B.A.M. is a Canada Research Chair and a MSFHR Distinguished Scholar. G.C.R.E.-D. is supported through an NIH operating grant \# GM53395. J.S.B. is an AHFMR Senior Scholar. This research was funded by operating grants from the Canadian Institutes for Health Research (CIHR) and the HSFC. G.R.J.G. performed the majority of the experiments and analysis described and wrote the manuscript. K.J.I. assisted in astrocyte recordings, analysis of astrocyte membrane properties, and performed some of the afferent stimulation experiments. G.C.R.E.-D. and S.K. synthesized and provided the NV-IP 3 /AM. B.A.M. supervised and contributed to the design of the two-photon experiments. J.S.B. supervised the project, performed some of the multiplicative scaling analysis, and wrote the manuscript. All authors helped edit the manuscript. ",
year = "2009",
month = nov,
day = "12",
doi = "10.1016/j.neuron.2009.10.021",
language = "English",
volume = "64",
pages = "391--403",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "3",
}