Chronic vagotomy induces nTS glial activation, reduced glutamatergic signaling, and blunted cardiorespiratory responses
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The brainstem nucleus tractus solitarii (nTS) is the first site of integration of viscerosensory information provided by afferents of the vagus nerves. The nTS critically contributes to cardiorespiratory function and displays remarkable neuroplasticity in response to changes in afferent input. Vagal afferents form synapses with nTS neurons that are closely associated with astrocytes, forming the tripartite synapse. We hypothesized that reducing vagal afferent input via chronic unilateral vagotomy would alter tripartite synapse function in the nTS, resulting in changes in cardiorespiratory activity. In the results of Aim 1, we showed that vagotomy induced astrocyte reactivity and microglial activation in the nTS. This corresponded to a reduction in augmented breaths (sighs) during hypoxia. In Aim 2, we further investigated the effects of vagotomy by stimulating vagal afferents and recording cardiorespiratory and sympathetic responses. Blunted responses to stimulation lead us to hypothesize that the reactive astrocytes at the tripartite synapse may be contributing to this response through increased glutamate uptake. Instead we found evidence of reduced excitability of vagotomized afferents and decreased postsynaptic NMDA receptor function, leading to blunted nTS neuronal activation upon stimulation. Together these results demonstrate that multiple changes occur at the tripartite synapse following vagotomy, and these effects contribute to reduced reflex responses that may affect cardiorespiratory function in health and disease.
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Ph. D.