Synaptic Efficacy Enhanced by Glial Cells in Vitro

Pfrieger, Frank W.; Barres, Barbara A.

doi:10.1126/science.277.5332.1684

Cited by 709 publications

(504 citation statements)

References 18 publications

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“…These behavioral studies argue for the involvement of LIF in postnatal brain development at least in part through alterations in glia. The importance of astrocytes and morphological contacts formed between astrocytic processes and synapses is apparent as astrocytes and astrocyte-conditioned media promote synapse formation (Pfrieger and Barres, 1997;Ullian et al, 2001) and both LTP and LTD are affected by astrocytes acting through several mechanisms. Astrocytes directly regulate NMDA-receptor-dependent LTP and plasticity through glial-derived D-serine (Yang et al, 2003;Panatier et al, 2006), ATP and adenosine (Pascual et al, 2005;Fields and Burnstock, 2006), glutamate reuptake and release (Haydon and Carmignoto, 2006) and extracellular K + handling (Wallraff et al, 2006;Djukic et al, 2007;Ge and Duan, 2007).…”

Section: Discussionmentioning

confidence: 99%

Activity-dependent neuron–glial signaling by ATP and leukemia-inhibitory factor promotes hippocampal glial cell development

Cohen

Fields

2008

Neuron Glia Biol.

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Activity-dependent signaling between neurons and astrocytes contributes to experience-dependent plasticity and development of the nervous system. However, mechanisms responsible for neuronglial interactions and the releasable factors that underlie these processes are not well understood. The pro-inflammatory cytokine, leukemia-inhibitory factor (LIF), is transiently expressed postnatally by glial cells in the hippocampus and rapidly up-regulated by enhanced neural activity following seizures. To test the hypothesis that spontaneous neural activity regulates glial development in hippocampus via LIF signaling, we blocked spontaneous activity with the sodium channel blocker tetrodotoxin (TTX) in mixed hippocampal cell cultures in combination with blockers of LIF and purinergic signaling. TTX decreased the number of GFAP-expressing astrocytes in hippocampal cell culture. Furthermore, blocking purinergic signaling by P2Y receptors contributed to reduced numbers of astrocytes. Blocking activity or purinergic signaling in the presence of function-blocking antibodies to LIF did not further decrease the number of astrocytes. Moreover, hippocampal cell cultures prepared from LIF −/− mice had reduced numbers of astrocytes and activity-dependent neuron-glial signaling promoting differentiation of astrocytes was absent. The results show that endogenous LIF is required for normal development of hippocampal astrocytes, and this process is regulated by spontaneous neural impulse activity through the release of ATP.

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Section: Discussionmentioning

confidence: 99%

Activity-dependent neuron–glial signaling by ATP and leukemia-inhibitory factor promotes hippocampal glial cell development

Cohen

Fields

2008

Neuron Glia Biol.

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“…Astrocytes induce a dramatic increase in synapse formation, and in spontaneous synaptic activity in cultured retinal ganglion cells (Pfrieger and Barres, 1997). Astrocytes also increase the number of functional synapses on CNS neurons sevenfold, and are required for maintenance of synapses in vitro (Ullian et al, 2001).…”

Section: Glia-another Source Of Extrinsic Regulatory Signalsmentioning

confidence: 99%

Regulatory mechanisms that govern nicotinic synapse formation in neurons

et al. 2002

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Individual cholinoceptive neurons express high levels of different neuronal nicotinic acetylcholine receptor (nAChR) subtypes, and target them to the appropriate synaptic regions for proper function. This review focuses on the intercellular and intracellular processes that regulate nAChR expression in vertebrate peripheral nervous system (PNS) and central nervous system (CNS) neurons. Specifically, we discuss the cellular and molecular mechanisms that govern the induction and maintenance of nAChR expression-innervation, target tissue interactions, soluble factors, and activity. We define the regulatory principles of interneuronal nicotinic synapse differentiation that have emerged from these studies. We also discuss the molecular players that target nAChRs to the surface membrane and the interneuronal synapse.

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“…Carefully controlled studies of retinal ganglion cells cultured in Neurobasal/B27 serum-free medium monitored by patchclamp produced more and higher amplitude postsynaptic currents after 20 days of culture when astroglia were added to the cultures at day 5 (Pfrieger and Barres, 1997). When the effects of added astroglia were mimicked by glia-conditioned medium, the effects were attributed to trophic factors released by astroglia.…”

Section: Introductionmentioning

confidence: 99%

Added astroglia promote greater synapse density and higher activity in neuronal networks

2007

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Astroglia are known to potentiate individual synapses, but their contribution to networks is unclear.Here we examined the effect of adding either astroglia or media conditioned by astroglia on entire networks of rat hippocampal neurons cultured on microelectrode arrays. Added astroglia increased spontaneous spike rates nearly two-fold and glutamate-stimulated spiking by six-fold, with desensitization eliminated for bath addition of 25 μM glutamate. Astrocyte-conditioned medium partly mimicked the effects of added astroglia. Bursting behavior was largely unaffected by added astroglia except with added glutamate. Addition of the GABA A receptor antagonist bicuculline also increased spike rates but with more subtle differences between networks without or with added astroglia. This indicates that networks without added astroglia were inhibited greatly. In all conditions, the log-log distribution of spike rates fit well to linear distributions over three orders of magnitude. Networks with added astroglia shifted consistently toward higher spike rates. Immunostaining for GFAP revealed a linear increase with added astroglia, which also increased neuronal survival. The increased spike rates with added astroglia correlated with a 1.7-fold increase in immunoreactive synaptophysin puncta, and increases of six-fold for GABA Aβ , two-fold for NMDA-R1 and two-fold for Glu-R1 puncta, with receptor clustering that indicated synaptic scaling. Together, these results indicate that added astroglia increase the density of synapses and receptors, and facilitate higher spike rates for many elements in the network. These effects are reproduced by glia-conditioned media, with the exception of glutamate-mediated transmission.

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Synaptic Efficacy Enhanced by Glial Cells in Vitro

Cited by 709 publications

References 18 publications

Activity-dependent neuron–glial signaling by ATP and leukemia-inhibitory factor promotes hippocampal glial cell development

Activity-dependent neuron–glial signaling by ATP and leukemia-inhibitory factor promotes hippocampal glial cell development

Regulatory mechanisms that govern nicotinic synapse formation in neurons

Added astroglia promote greater synapse density and higher activity in neuronal networks

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