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

Yamamoto, Keizô; Mifflin, Steve

doi:10.14814/phy2.13877

Cited by 6 publications

(9 citation statements)

References 43 publications

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“…In line with their role in integrating activity at the ST-NTS synapse, glutamate reuptake and recycling by NTS astrocytes is crucial for cardiovascular function. Blockade of all EAATs (by TBOA) or only EAAT2 (by DHK) causes cardiac depression and reduced baroreflex response to phenylephrine in rats [49] , [50] , [51] . This effect is blocked by kynurenate (an ionotropic glutamate receptor antagonist) and NBQX (an AMPA-R antagonist) suggesting that under normal conditions NTS astrocytes sequester synaptic glutamate in order to regulate NTS neuronal activity and resulting output from DMX neurons to the cardiorespiratory system [ 50 , 51 ].…”

Section: Regulation Of Physiology By Nts Astrocytesmentioning

confidence: 98%

“…Excitatory amino acid transporter 1 (EAAT1) and EAAT2, are expressed primarily by astrocytes [48] . In the NTS this astrocytic glutamate reuptake appears to be essential for normal synaptic function [49] , [50] , [51] . Pharmacological blockade of both EAAT1 and EAAT2 with DL- threo -β-benzyloxyaspartic acid (TBOA) elevates synaptic glutamate as evidenced by NTS neuronal depolarisation and action potential firing, and increased spontaneous EPSCs [49] .…”

Section: Astrocytes Modulate Synaptic Transmission In the Ntsmentioning

confidence: 99%

“…Furthermore in NTS neurons, ST-evoked EPSCs are reduced by TBOA suggesting released glutamate is not being returned to the presynaptic terminal [49] . These effects can be recapitulated by dihydrokainate (DHK), an EAAT2 blocker [ 50 , 51 ]. In combination with immunohistochemical evidence [26] , this indicates that EAAT2 is the primary glutamate transporter responsible for glutamate reuptake and recycling at the ST-NTS synapse [ 50 , 51 ].…”

Section: Astrocytes Modulate Synaptic Transmission In the Ntsmentioning

confidence: 99%

“…These effects can be recapitulated by dihydrokainate (DHK), an EAAT2 blocker [ 50 , 51 ]. In combination with immunohistochemical evidence [26] , this indicates that EAAT2 is the primary glutamate transporter responsible for glutamate reuptake and recycling at the ST-NTS synapse [ 50 , 51 ]. Glutamate transporters on astrocytes appear to be pH sensitive since synaptic glutamate accumulates at pH 7.0, suggesting they may play an additional chemosensory role [52] .…”

Section: Astrocytes Modulate Synaptic Transmission In the Ntsmentioning

confidence: 99%

“…Thus, combined evidence from a number of independent research groups shows that astrocytes support synaptic transmission in the NTS by buffering and recycling synaptic glutamate [49] , [50] , [51] , shuttling lactate to neurons [41] and providing tonic purinergic neuromodulation [ 28 , 38 ] ( Fig. 1 ).…”

Section: Astrocytes Modulate Synaptic Transmission In the Ntsmentioning

confidence: 99%

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Astrocytes in the nucleus of the solitary tract: Contributions to neural circuits controlling physiology

Macdonald

Ellacott

2020

Physiology & Behavior

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The nucleus of the solitary tract (NTS) is the primary brainstem centre for the integration of physiological information from the periphery transmitted via the vagus nerve. In turn, the NTS feeds into downstream circuits regulating physiological parameters. Astrocytes are glial cells which have key roles in maintaining CNS tissue homeostasis and regulating neuronal communication. Recently an increasing number of studies have implicated astrocytes in the regulation of synaptic transmission and physiology. This review aims to highlight evidence for a role for astrocytes in the functions of the NTS. Astrocytes maintain and modulate NTS synaptic transmission contributing to the control of diverse physiological systems namely cardiovascular, respiratory, glucoregulatory, and gastrointestinal. In addition, it appears these cells may have a role in central control of feeding behaviour. As such these cells are a key component of signal processing and physiological control by the NTS.

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Section: Regulation Of Physiology By Nts Astrocytesmentioning

confidence: 98%

Section: Astrocytes Modulate Synaptic Transmission In the Ntsmentioning

confidence: 99%

Section: Astrocytes Modulate Synaptic Transmission In the Ntsmentioning

confidence: 99%

Section: Astrocytes Modulate Synaptic Transmission In the Ntsmentioning

confidence: 99%

Section: Astrocytes Modulate Synaptic Transmission In the Ntsmentioning

confidence: 99%

See 3 more Smart Citations

Astrocytes in the nucleus of the solitary tract: Contributions to neural circuits controlling physiology

Macdonald

Ellacott

2020

Physiology & Behavior

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Vagotomy blunts cardiorespiratory responses to vagal afferent stimulation via pre‐ and postsynaptic effects in the nucleus tractus solitarii

Hofmann,

Gama de Barcellos Filho,

Khodadadi

et al. 2024

The Journal of Physiology

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Viscerosensory information travels to the brain via vagal afferents, where it is first integrated within the brainstem nucleus tractus solitarii (nTS), a critical contributor to cardiorespiratory function and site of neuroplasticity. We have shown that decreasing input to the nTS via unilateral vagus nerve transection (vagotomy) induces morphological changes in nTS glia and reduces sighs during hypoxia. The mechanisms behind post‐vagotomy changes are not well understood. We hypothesized that chronic vagotomy alters cardiorespiratory responses to vagal afferent stimulation via blunted nTS neuronal activity. Male Sprague–Dawley rats (6 weeks old) underwent right cervical vagotomy caudal to the nodose ganglion, or sham surgery. After 1 week, rats were anaesthetized, ventilated and instrumented to measure mean arterial pressure (MAP), heart rate (HR), and splanchnic sympathetic and phrenic nerve activity (SSNA and PhrNA, respectively). Vagal afferent stimulation (2–50 Hz) decreased cardiorespiratory parameters and increased neuronal Ca2+ measured by in vivo photometry and in vitro slice imaging of nTS GCaMP8m. Vagotomy attenuated both these reflex and neuronal Ca2+ responses compared to shams. Vagotomy also reduced presynaptic Ca2+ responses to stimulation (Cal‐520 imaging) in the nTS slice. The decrease in HR, SSNA and PhrNA due to nTS nanoinjection of exogenous glutamate also was tempered following vagotomy. This effect was not restored by blocking excitatory amino acid transporters. However, the blunted responses were mimicked by NMDA, not AMPA, nanoinjection and were associated with reduced NR1 subunits in the nTS. Altogether, these results demonstrate that vagotomy induces multiple changes within the nTS tripartite synapse that influence cardiorespiratory reflex responses to afferent stimulation. imageKey points Multiple mechanisms within the nucleus tractus solitarii (nTS) contribute to functional changes following vagal nerve transection. Vagotomy results in reduced cardiorespiratory reflex responses to vagal afferent stimulation and nTS glutamate nanoinjection. Blunted responses occur via reduced presynaptic Ca2+ activation and attenuated NMDA receptor expression and function, leading to a reduction in nTS neuronal activation. These results provide insight into the control of autonomic and respiratory function, as well as the plasticity that can occur in response to nerve damage and cardiorespiratory disease.

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The role of astrocytes in the nucleus tractus solitarii in maintaining central control of autonomic function

Martínez

Kline

2021

American Journal of Physiology-Regulatory, Integrative and Comp

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The nucleus Tractus Solitarii (nTS) is the first central site for the termination and integration of autonomic and respiratory sensory information. Sensory afferents terminating in the nTS as well as the embedded nTS neurocircuitry release and utilize glutamate that is critical for maintenance of baseline cardiorespiratory parameters and initiating cardiorespiratory reflexes, including those activated by bouts of hypoxia. nTS astrocytes contribute to synaptic and neuronal activity through a variety of mechanisms, including gliotransmission and regulation of glutamate in the extracellular space via membrane-bound transporters. Here, we aim to highlight recent evidence for the role of astrocytes within the nTS and their regulation of autonomic and cardiorespiratory processes under normal and hypoxic conditions.

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

Cited by 6 publications

References 43 publications

Astrocytes in the nucleus of the solitary tract: Contributions to neural circuits controlling physiology

Astrocytes in the nucleus of the solitary tract: Contributions to neural circuits controlling physiology

Vagotomy blunts cardiorespiratory responses to vagal afferent stimulation via pre‐ and postsynaptic effects in the nucleus tractus solitarii

The role of astrocytes in the nucleus tractus solitarii in maintaining central control of autonomic function

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