Mastitskaya, S;
Turovsky, E;
Marina, N;
Theparambil, SM;
Hadjihambi, A;
Kasparov, S;
Teschemacher, AG;
... Hosford, PS; + view all
(2020)
Astrocytes modulate baroreflex sensitivity at the level of the nucleus of the solitary tract.
The Journal of Neuroscience
, 40
(15)
pp. 3052-3062.
10.1523/JNEUROSCI.1438-19.2020.
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Gourine_Astrocytes modulate baroreflex sensitivity at the level of the nucleus of the solitary tract_AAM.pdf - Accepted Version Download (9MB) | Preview |
Abstract
Maintenance of cardiorespiratory homeostasis depends on autonomic reflexes controlled by neuronal circuits of the brainstem. The neurophysiology and neuroanatomy of these reflex pathways are well understood, however, the mechanisms and functional significance of autonomic circuit modulation by glial cells remain largely unknown. In experiments conducted in male laboratory rats we show that astrocytes of the nucleus tractus solitarii (NTS), the brain area that receives and integrates sensory information from the heart and blood vessels, respond to incoming afferent inputs with [Ca2+]i elevations. Astroglial [Ca2+]i responses are triggered by transmitters released by vagal afferents, glutamate acting at AMPA receptors and 5-HT acting at 5-HT2A receptors. In conscious freely behaving animals blockade of Ca2+-dependent vesicular mechanisms in NTS astrocytes by virally driven expression of a dominant-negative SNARE protein (dnSNARE) increased baroreflex sensitivity by 70% (p<0.001). The effect of compromised astroglial function was specific to the NTS as expression of dnSNARE in astrocytes of the ventrolateral brainstem had no effect. ATP considered the principle gliotransmitter and is released by vesicular mechanisms affected by dnSNARE expression. Consistent with this hypothesis, in anesthetized rats, activation P2Y1 purinoceptors in the NTS decreased baroreflex gain by 40% (p=0.031), while blockade of P2Y1 receptors increased baroreflex gain by 57% (p=0.018). These results suggest that glutamate and 5-HT released by NTS afferent terminals trigger Ca2+-dependent astroglial release of ATP to modulate baroreflex sensitivity via P2Y1 receptors. These data add to the growing body of evidence supporting an active role of astrocytes in the brain information processing.
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