Glia Contribute to the Purinergic Modulation of Inspiratory Rhythm-Generating Networks

Huxtable, Adrianne G.; Zwicker, Jennifer; Alvares, Tucaauê S.; Ruangkittisakul, Araya; Fang, Xin; Hahn, Leanne B; Chaves, E; Baker, Glen B.; Ballanyi, Klaus; Funk, Gregory D.

doi:10.1523/jneurosci.6027-09.2010

Cited by 89 publications

(111 citation statements)

References 55 publications

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“…While these findings suggest that astrocytes do not directly modify neuronal activity in the pre-Bö tC, astrocytes may nonetheless be important for the maintenance of the respiratory rhythm generation in this complex. For instance, the astrocyte inhibitor methionine sulfoximine depresses breathing in vivo (Young et al, 2005), and glial inhibitors (fluorocitrate, fluoroacetate, and methionine sulfoximine) reduce respiratory-related activity in the preBö tC in vitro (Erlichman et al, 1998;Huxtable et al, 2010). We have not examined such inhibition of astrocytes in the present study.…”

Section: Resultsmentioning

confidence: 91%

Astrocytes release prostaglandin E2 to modify respiratory network activity

Forsberg

Ringstedt

Herlenius

2017

Preprint

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Previously (Forsberg et al., 2016), we revealed that prostaglandin E2 (PGE2), released during hypercapnic challenge, increases calcium oscillations in the chemosensitive parafacial respiratory group (pFRG/RTN). Here, we demonstrate that pFRG/RTN astrocytes are the PGE2 source. Two distinct astrocyte subtypes were found using transgenic mice expressing GFP and MrgA1 receptors in astrocytes. Although most astrocytes appeared dormant during time-lapse calcium imaging, a subgroup displayed persistent, rhythmic oscillating calcium activity. These active astrocytes formed a subnetwork within the respiratory network distinct from the neuronal network. Activation of exogenous MrgA1Rs expressed in astrocytes tripled astrocytic calcium oscillation frequency in both the preBö tzinger complex and pFRG/RTN. However, neurons in the preBö tC were unaffected, whereas neuronal calcium oscillatory frequency in pFRG/RTN doubled. Notably, astrocyte activation in pFRG/RTN triggered local PGE2 release and blunted the hypercapnic response. Thus, astrocytes play an active role in respiratory rhythm modulation, modifying respiratory-related behavior through PGE2 release in the pFRG/RTN.

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Section: Resultsmentioning

confidence: 91%

Astrocytes release prostaglandin E2 to modify respiratory network activity

Forsberg

Ringstedt

Herlenius

2017

Preprint

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“…7E does not. Since it has been suggested that NE and ATP evoke Ca 2ϩ signals selectively in astrocytes (Duffy and MacVicar 1995;Fu et al 2013;Huxtable et al 2010), the recordings in Fig. 7E may originate from a neuron and those in Fig.…”

Section: Resultsmentioning

confidence: 99%

Analysis of the long-term actions of gabapentin and pregabalin in dorsal root ganglia and substantia gelatinosa

Biggs

Boakye

Ganesan

et al. 2014

Journal of Neurophysiology

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of the long-term actions of gabapentin and pregabalin in dorsal root ganglia and substantia gelatinosa. J Neurophysiol 112: 2398 -2412, 2014. First published August 13, 2014; doi:10.1152/jn.00168.2014.-The ␣2␦-ligands pregabalin (PGB) and gabapentin (GBP) are used to treat neuropathic pain. We used whole cell recording to study their long-term effects on substantia gelatinosa and dorsal root ganglion (DRG) neurons. Spinal cord slices were prepared from embryonic day 13 rat embryos and maintained in organotypic culture for Ͼ5 wk (neuronal age equivalent to young adult rats). Exposure of similarly aged DRG neurons (dissociated and cultured from postnatal day 19 rats) to GBP or PGB for 5-6 days attenuated high-voltage-activated calcium channel currents (HVA I Ca ). Strong effects were seen in medium-sized and in small isolectin B 4 -negative (IB 4 Ϫ) DRG neurons, whereas large neurons and small neurons that bound isolectin B 4 (IB 4 ϩ) were hardly affected. GBP (100 M) or PGB (10 M) were less effective than 20 M Mn 2ϩ in suppression of HVA I Ca in small DRG neurons. By contrast, 5-6 days of exposure to these ␣2␦-ligands was more effective than 20 M Mn 2ϩ in reducing spontaneous excitatory postsynaptic currents at synapses in substantia gelatinosa. Spinal actions of gabapentinoids cannot therefore be ascribed to decreased expression of HVA Ca 2ϩ channels in primary afferent nerve terminals. In substantia gelatinosa, 5-6 days of exposure to PGB was more effective in inhibiting excitatory synaptic drive to putative excitatory neurons than to putative inhibitory neurons. Although spontaneous inhibitory postsynaptic currents were also attenuated, the overall long-term effect of ␣2␦-ligands was to decrease network excitability as monitored by confocal Ca 2ϩ imaging. We suggest that selective actions of ␣2␦-ligands on populations of DRG neurons may predict their selective attenuation of excitatory transmission onto excitatory vs. inhibitory neurons in substantia gelatinosa.

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“…Astrocytes in the brainstem chemoreceptor area are highly chemosensitive; they respond to decreases in pH with increases in [Ca 2ϩ ] i and release of ATP, which led to activation of chemosensitive neurons and induced adaptive increases in breathing . It was demonstrated that PBC glia also respond to ATP, with increased [Ca 2ϩ ] i and glutamate release, and may therefore contribute to the ATP sensitivity of PBC networks and possibly to the hypoxic ventilatory response (Huxtable et al, 2010).…”

Section: Central Control Of Respirationmentioning

confidence: 99%