PMID- 28899919
OWN - NLM
STAT- MEDLINE
DCOM- 20171023
LR  - 20190114
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 37
IP  - 41
DP  - 2017 Oct 11
TI  - Astrocyte-Mediated Neuronal Synchronization Properties Revealed by False 
      Gliotransmitter Release.
PG  - 9859-9870
LID - 10.1523/JNEUROSCI.2761-16.2017 [doi]
AB  - Astrocytes spontaneously release glutamate (Glut) as a gliotransmitter (GT), 
      resulting in the generation of extrasynaptic NMDAR-mediated slow inward currents 
      (SICs) in neighboring neurons, which can increase local neuronal excitability. 
      However, there is a deficit in our knowledge of the factors that control 
      spontaneous astrocyte GT release and the extent of its influence. We found that, 
      in rat brain slices, increasing the supply of the physiological transmitter Glut 
      increased the frequency and signaling charge of SICs over an extended period. 
      This phenomenon was replicated by exogenous preexposure to the amino acid 
      D-aspartate (D-Asp). Using D-Asp as a "false" GT, we determined the extent of 
      local neuron excitation by GT release in ventrobasal thalamus, CA1 hippocampus, 
      and somatosensory cortex. By analyzing synchronized neuronal NMDAR-mediated 
      excitation, we found that the properties of the excitation were conserved in 
      different brain areas. In the three areas, astrocyte-derived GT release 
      synchronized groups of neurons at distances of >;200 mum. Individual neurons 
      participated in more than one synchronized population, indicating that individual 
      neurons can be excited by more than one astrocyte and that individual astrocytes 
      may determine a neuron's synchronized network. The results confirm that 
      astrocytes can act as excitatory nodes that can influence neurons over a 
      significant range in a number of brain regions. Our findings further suggest that 
      chronic elevation of ambient Glut levels can lead to increased GT Glut release, 
      which may be relevant in some pathological states.SIGNIFICANCE STATEMENT 
      Astrocytes spontaneously release glutamate (Glut) and other gliotransmitters 
      (GTs) that can modify neuronal activity. Exposing brain slices to Glut and 
      D-aspartate (D-Asp) before recording resulted in an increase in frequency of 
      GT-mediated astrocyte-neuron signaling. Using D-Asp, it was possible to 
      investigate the effects of specific GT release at neuronal NMDARs. Calcium 
      imaging showed synchronized activity in groups of neurons in cortex, hippocampus, 
      and thalamus. The size of these populations was similar in all areas and some 
      neurons were involved in more than one synchronous group. The findings show that 
      GT release is supply dependent and that the properties of the signaling and 
      activated networks are largely conserved between different brain areas.
CI  - Copyright (c) 2017 Pirttimaki, Sims et al.
FAU - Pirttimaki, Tiina M
AU  - Pirttimaki TM
AD  - School of Life and Health Sciences, Aston University, Birmingham B4 7ET, United 
      Kingdom.
FAU - Sims, Robert E
AU  - Sims RE
AD  - School of Life and Health Sciences, Aston University, Birmingham B4 7ET, United 
      Kingdom.
FAU - Saunders, Gregory
AU  - Saunders G
AD  - School of Life and Health Sciences, Aston University, Birmingham B4 7ET, United 
      Kingdom.
FAU - Antonio, Serena A
AU  - Antonio SA
AD  - School of Life and Health Sciences, Aston University, Birmingham B4 7ET, United 
      Kingdom.
FAU - Codadu, Neela Krushna
AU  - Codadu NK
AD  - School of Life and Health Sciences, Aston University, Birmingham B4 7ET, United 
      Kingdom.
FAU - Parri, H Rheinallt
AU  - Parri HR
AUID- ORCID: 0000-0002-1412-2688
AD  - School of Life and Health Sciences, Aston University, Birmingham B4 7ET, United 
      Kingdom parrihr@aston.ac.uk.
LA  - eng
GR  - BB/J017809/Biotechnology and Biological Sciences Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170912
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Neurotransmitter Agents)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 30KYC7MIAI (Aspartic Acid)
RN  - 3KX376GY7L (Glutamic Acid)
SB  - IM
MH  - Animals
MH  - Aspartic Acid/metabolism
MH  - Astrocytes/*physiology
MH  - Brain Chemistry
MH  - CA1 Region, Hippocampal/cytology/metabolism
MH  - Female
MH  - Glutamic Acid/metabolism
MH  - In Vitro Techniques
MH  - Male
MH  - Neuroglia/metabolism/*physiology
MH  - Neurons/*physiology
MH  - Neurotransmitter Agents/metabolism/*physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
MH  - Somatosensory Cortex/cytology/metabolism
MH  - Thalamus/cytology/metabolism
PMC - PMC5637115
OTO - NOTNLM
OT  - EAAT
OT  - cortex
OT  - glia
OT  - thalamus
EDAT- 2017/09/14 06:00
MHDA- 2017/10/24 06:00
PMCR- 2017/10/11
CRDT- 2017/09/14 06:00
PHST- 2016/08/26 00:00 [received]
PHST- 2017/06/14 00:00 [revised]
PHST- 2017/06/27 00:00 [accepted]
PHST- 2017/09/14 06:00 [pubmed]
PHST- 2017/10/24 06:00 [medline]
PHST- 2017/09/14 06:00 [entrez]
PHST- 2017/10/11 00:00 [pmc-release]
AID - JNEUROSCI.2761-16.2017 [pii]
AID - 2761-16 [pii]
AID - 10.1523/JNEUROSCI.2761-16.2017 [doi]
PST - ppublish
SO  - J Neurosci. 2017 Oct 11;37(41):9859-9870. doi: 10.1523/JNEUROSCI.2761-16.2017. 
      Epub 2017 Sep 12.