The excitatory amino acid carrier 1 (EAAC1) in the rat nucleus of the solitary tract: subcellular localization suggests no major role in glutamate clearance

Chounlamountry, Keodavanh; Castets, Francis; Tell, Fabien; Kessler, Jean-Pierre

doi:10.1007/s00429-014-0958-7

Cited by 6 publications

(6 citation statements)

References 38 publications

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“…As others have suggested (Chounlamountry et al. ), it is unlikely that changes in EAAC1 in the NTS participate in glutamate clearance or in excitation of glutamate receptors and are thus, an unlikely explanation for changes in physiological responses to activation of glutamate receptors as shown in this study.…”

Section: Discussionsupporting

confidence: 59%

Reduced responses to glutamate receptor agonists follow loss of astrocytes and astroglial glutamate markers in the nucleus tractus solitarii

Talman

Dragon

Lin

2017

Physiological Reports

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Saporin (SAP) or SAP conjugates injected into the nucleus tractus solitarii (NTS) of rats kill astrocytes. When injected in its unconjugated form, SAP produces no demonstrable loss of or damage to local neurons. However bilateral injections of SAP significantly attenuate responses to activation of baroreceptor reflexes that are mediated by transmission of signals through glutamate receptors in the NTS. We tested the hypothesis that SAP would reduce cardiovascular responses to activation of NTS glutamate receptors despite its recognized ability to spare local neurons while killing local astrocytes. In animals treated with SAP and SAP conjugates or, as a control, with the toxin 6‐hydroxydopamine (6‐OHDA), we sought to determine if dose‐related changes of arterial pressure (AP) or heart rate (HR) in response to injection into NTS of N‐methyl‐d‐aspartate (NMDA) or α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) were attenuated. Also we quantified changes in immunoreactivity (IR) for EAAT2, EAAC1, and VGluT2 in NTS after SAP and SAP conjugates. Our earlier studies showed that IR for NMDA and AMPA receptors was not changed after injection of SAP. We found that EAAT2 and EAAC1, both found in astrocytes, were reduced by SAP or its conjugates but not by 6‐OHDA. In contrast, VGluT2‐IR was increased by SAP or conjugates but not by 6‐OHDA. AP and HR responses to NMDA and AMPA were attenuated after SAP and SAP conjugate injection but not after 6‐OHDA. Results of this study are consistent with others that have shown interactions between astroglia and neurons in synaptic transmission mediated by glutamate receptor activation in the NTS.

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Section: Discussionsupporting

confidence: 59%

Reduced responses to glutamate receptor agonists follow loss of astrocytes and astroglial glutamate markers in the nucleus tractus solitarii

Talman

Dragon

Lin

2017

Physiological Reports

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“…For instance, TBOA inhibits astrocytic EAAT1‐2 and neuronal EAAT3 (although EAAT3 likely does not play a profound role; Chounlamountry et al . ). Block of both EAAT1 and EAAT2 with TBOA may result in greater elevation of [Glu] e than EAAT2 block alone, and thus activate receptors more distal from the sensory afferent–nTS synaptic active zone to ultimately inhibit TS‐EPSC amplitude (e.g.…”

Section: Discussionmentioning

confidence: 97%

“…The observed difference between TBOA-and DHK-mediated changes in TS-EPSCs may be due to the magnitude of elevation of [Glu] e via EAAT block, and/or the mechanism by which the increase occurs. For instance, TBOA inhibits astrocytic EAAT1-2 and neuronal EAAT3 (although EAAT3 likely does not play a profound role; Chounlamountry et al 2016). Block of both EAAT1 and EAAT2 with TBOA may result in greater elevation of [Glu] e than EAAT2 block alone, and thus activate receptors more distal from the sensory afferent-nTS synaptic active zone to ultimately inhibit TS-EPSC amplitude (e.g.…”

Section: Discussionmentioning

confidence: 99%

Glial EAAT2 regulation of extracellular nTS glutamate critically controls neuronal activity and cardiorespiratory reflexes

Matott

Kline

Hasser

2017

The Journal of Physiology

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Glutamatergic signalling is critical in the nucleus tractus solitarii (nTS) for cardiorespiratory homeostasis and initiation of sensory reflexes, including the chemoreflex activated during hypoxia. Maintenance of nTS glutamate concentration occurs in part through astrocytic excitatory amino acid transporters (EAATs). We previously established the importance of EAATs in the nTS by demonstrating their inhibition produced neuronal excitation to alter basal cardiorespiratory function. Since EAAT2 is the most expressed EAAT in the nTS, this study specifically determined EAAT2's role in nTS astrocytes, its influence on neuronal and synaptic properties, and ultimately on basal and reflex cardiorespiratory function. The EAAT2-specific antagonist dihydrokainate (DHK) was microinjected into the anaesthetized rat nTS or applied to rat nTS slices. DHK produced depressor, bradycardic and sympathoinhibitory responses and reduced neural respiration in the intact rat, mimicking responses to glutamate excitation. DHK also enhanced responses to glutamate microinjection. DHK elevated extracellular nTS glutamate concentration, depolarized neurons and enhanced spontaneous EPSCs. EAAT2 block also augmented action potential discharge in chemosensitive nTS neurons. Glial recordings confirmed EAAT2 is functional on nTS astrocytes. Neuronal excitation and cardiorespiratory effects following EAAT2 inhibition were due to activation of putative extrasynaptic AMPA receptors as their antagonism blocked DHK responses in the intact rat nTS and the slice. The DHK-induced elevation of extracellular glutamate and neuronal excitation augmented chemoreflex-mediated pressor, sympathoexcitatory and minute neural ventilation responses in the rat. These data shed new light on the important role astrocytic EAAT2 plays on buffering nTS excitation and overall cardiorespiratory function.

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“…Although the main glutamate transporter expressed by astrocytes in the NTS is GLT1 (Chounlamountry and Kessler 2011), function in other glutamate transporters such as glutamate/aspartate transporter (GLAST; EAAT1) on astrocytes and excitatory amino acid carrier 1 (EAAC1; EAAT3) on neurons were intact in the NTS. However, it is unlikely that EAAC1 in NTS plays a major role in glutamate clearance (Chounlamountry et al 2016). The inhibition of GLT1 in the present study dramatically decreased MAP, RSNA, and HR (Fig.…”

Section: Discussionmentioning

confidence: 45%

“…However, it is unlikely that EAAC1 in NTS plays a major role in glutamate clearance (Chounlamountry et al. ). The inhibition of GLT1 in the present study dramatically decreased MAP, RSNA, and HR (Fig.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of glial glutamate transporter GLT1 in the nucleus of the solitary tract attenuates baroreflex control of sympathetic nerve activity and heart rate

Yamamoto

Mifflin

2018

Physiol Rep

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The astrocytic glutamate transporter (GLT1) plays an important role in the maintenance of extracellular glutamate concentration below neurotoxic levels in brain. However, the functional role of GLT1 within the nucleus of the solitary tract (NTS) in the regulation of cardiovascular function remains unclear. We examined the effect of inhibiting GLT1 in the subpostremal NTS on mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA) and heart rate (HR) in anesthetized, artificially ventilated rats. It was found that dihydrokainate (DHK; inhibitor of GLT1, 5 mmol/L, 100 nL) injections into the NTS (n = 6) decreased MAP (50 ± 10 mmHg, mean ± SD), RSNA (89 ± 14%) and HR (37 ± 6 bpm). Pretreatment with kynurenate (KYN; glutamate receptor antagonist, 5 mmol/L, 30 μL) topically applied to the dorsal surface of the brainstem (n = 4) attenuated the responses to NTS injections of DHK (P < 0.01). The effect of DHK on arterial baroreflex function was examined using i.v. infusions of phenylephrine and nitroprusside. DHK reduced baroreflex response range (maximum−minimum) of RSNA by 91 ± 2% and HR by 83 ± 5% (n = 6, P < 0.001). These results indicate that inhibition of GLT1 within the NTS decreases MAP, RSNA, and HR by the activation of ionotropic glutamate receptors. As a result, baroreflex control of RSNA and HR was dramatically attenuated. The astrocytic glutamate transporter in the NTS plays an important role in the maintenance and regulation of cardiovascular function.

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The excitatory amino acid carrier 1 (EAAC1) in the rat nucleus of the solitary tract: subcellular localization suggests no major role in glutamate clearance

Cited by 6 publications

References 38 publications

Reduced responses to glutamate receptor agonists follow loss of astrocytes and astroglial glutamate markers in the nucleus tractus solitarii

Reduced responses to glutamate receptor agonists follow loss of astrocytes and astroglial glutamate markers in the nucleus tractus solitarii

Glial EAAT2 regulation of extracellular nTS glutamate critically controls neuronal activity and cardiorespiratory reflexes

Inhibition of glial glutamate transporter GLT1 in the nucleus of the solitary tract attenuates baroreflex control of sympathetic nerve activity and heart rate

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