Glia and the Synapse: Plasticity and Disease

A total of 78 pages for your doctor to use to make sure the stroke protocols being used for your 100% recovery are still correct. 
http://scholar.google.com/scholar_url?hl=en&q=http://downloads.hindawi.com/journals/specialissues/753103.pdf&sa=X&scisig=AAGBfm262Frk1J97GgQoqriYmR2udQKgBA&oi=scholaralrt
Department of Neuroscience, School of Medicine, University of Geneva, 1211-CH Geneva, Switzerland
2 Centre for Research in Neuroscience, Department of Neurology and Neurosurgery,
The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, QC, Canada H3G 1A4
3 Biological and Environmental Sciences & Engineering Division, King Abdullah University of Science and Technology,
Thuwal 23955, Saudi Arabia
Correspondence should be addressed to Irina Nikonenko; iryna.nikonenko@unige.ch
Received 3 February 2014; Accepted 3 February 2014; Published 18 March 2014
Copyright © 2014 Irina Nikonenko et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Glial cells play multiple, diverse roles in the central nervous
system (CNS), ranging from the basal support of
neuronal function to close partnership with the synapse.
Growing experimental evidence shows the importance of
glia for proper brain functioning and their involvement in
injury and disease. Astrocytes are the most intriguing cells
among the glial family. It is well known that they provide
energetic substrates to neurons, take up neurotransmitters,
and maintain ion homeostasis. Recent research has revealed
that they can also release gliotransmitters and signaling
molecules as well as maintain and regulate the extracellular
matrix. Structurally, astrocytic fine processes enwrap synaptic
contacts and exhibit remarkable plasticity resulting from
crosstalk between these compartments. These features endow
astrocytes with the ability to sense neuronal activity and integrate
and modulate synaptic transmission, revealing them as
a crucial element inmechanisms of synaptic transmission and
plasticity.
Indeed, astrocyte-synapse interactions are complex and
dynamic andare required fornormal synapticphysiology and
plasticity, as well as for the development and refinement of
the neuronal circuits. Although much progress has recently
been made in our understanding of the cellular andmolecular
mechanisms that underlie neuronal-glial interactions, ongoing
research is adding new information and new questions
regarding the role of glial cells in CNS development, function,
and disease.
In this special issue we collected research and review
articles that focus on glia-synapse interactions with a
particular focus on astrocytes. An important role played by
these cells in regulating long-term potentiation (LTP) and
memory mechanisms in hippocampus is reviewed by Y. Ota
et al. In the review “The role of astrocytes in the regulation
of synaptic plasticity and memory formation,” the authors
presented a summary of receptors and signaling molecules
implicated in LTP. In addition, they propose an integrative
model describing how astrocytes may modulate LTP at the
postsynaptic site. Supported by a growing number of studies,
their model confirms the involvement of the glutamatergic,
cholinergic, and purinergic pathways in the neuron-astrocyte
interactions taking place during synaptic plasticity.Moreover,
this cellular interplay implicates also ephrin signaling and
cytokines. Finally, Y. Ota and coauthors discuss the central
role played by astrocytic calciumand associated gliotransmitters
in hippocampal-dependent memory.
Although the primary function of astrocytes is to take up
glutamate to prevent excitotoxicity, astrocytes are also able to
release this neurotransmitter. This is generally well accepted
even if the mechanisms of release remain uncertain. In this
special issue, a novel mechanism of glutamate release from
astrocytes was studied by C. Cali et al. in the manuscript
“G-protein coupled receptor-evoked glutamate exocytosis from
astrocytes: role of prostaglandins.” They show the role of the
proinflammatorymediator prostaglandin E2 (PGE2) in glutamate
exocytosis fromastrocytes in the intact brain. Inhibition
of cyclooxygenase pathway caused a significant reduction in
the total number of fusion events of VGLUT1-positive glutamate
containing vesicles in astrocytes induced by activation
Hindawi Publishing Corporation
Neural Plasticity
Volume 2014, Article ID 246714, 2 pages
http://dx.doi.org/10.1155/2014/246714
2 Neural Plasticity
of purinergic and glutamatergic receptors. Prostaglandinmediated
signaling is implicated in the later, slower phase
of glutamate release and requires autocrine/paracrine action
of PGE2, suggesting a physiological role for this mediator in
intercellular communication, in addition to its known role in
inflammatory reactions in the brain.
Gliotransmitters glutamate and D-serine have been
shown to modulate NMDA receptors (NMDAR) at extrasynaptic
sites, revealing neuronal NMDAR as active components
of glia to neuron communication. In the review
“GluN3A: an NMDA receptor subunit with exquisite properties
and functions,” L. A. Kehoe et al. discuss recent data
on the GluN3A subunit which provides “nonconventional”
properties to NMDA receptors. Expression of this subunit
in early development helps to shape neuronal networks,
but it may also be implicated in different neuropathologies.
Interestingly, the presence of GluN3 subunit on perisynaptic
astrocytic processes suggests its possible involvement in
neuron-glia interactions, although more research is required
to elucidate this question.
Another mechanism used by astrocytes to regulate
intercellular interactions in the CNS is through secretion
of matricellular proteins. These proteins are nonstructural
molecules that regulate the extracellular matrix and cell-cell
interactions. In the paper “Astrocyte-secreted matricellular
proteins in CNS remodelling during development and disease,”
E. V. Jones and D. S. Bouvier review the roles of matricellular
proteins secreted from developing and reactive astrocytes
in CNS development, injury, and disease and discuss their
potential as therapeutic targets.
In the paper “Astrocyte-synapse structural plasticity,” Y.
Bernardinelli et al. review the data on plasticity of perisynaptic
astrocytic processes (PAPs). The authors discuss electron
and optical microscopy data showing the distribution of fine
astrocytic processes around synapses and overview growing
evidence on PAP structural plasticity. Although the exact
mechanisms and roles of this type of astrocytic plasticity
are still not clear, recent data has revealed a requirement
for neuronal activity and suggests that PAPs may be implicated
in the structural support and plasticity of a synapse,
control of neurotransmission and intersynaptic crosstalk,
energy supply,maintenance of extracellular homeostasis, and
integration of synaptic signals.
The study of glial structural plasticity (such as PAPs)
requires precise quantification of fine processes and their
motility. This challenging task is addressed in the paper
“Improved method for the quantification of motility in glia and
other morphologically complex cells” by M. Sild et al. who
propose and describe in detail a new approach to calculate a
motility index for cells with complex, dynamicmorphologies.
In this special issue, only some aspects out of a broad
range of topics on synapse-glia interactions are highlighted
and discussed. Despite great progress made recently in our
understanding of glia and their role in the CNS, there is still
a long road ahead. We hope that the data presented in this
issue will help the future research in this quickly growing and
important field.