AAS-Lundbeck Research Fellowship 2019

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Congratulations to our 2019 AAS-Lundbeck Research Fellowship awardee.


Title: Mechanisms underlying excitatory synaptic plasticity in the Nucleus Tractus Solitarii following Cardiovascular Deconditioning


Awardee: Dr. Ludmila Lima Silveira


Mentor: Dr. David Kline


Summary:

Orthostatic intolerance associated with cardiovascular deconditioning (CVD) is a clinical condition commonly observed in humans exposed to prolonged bed rest. Autonomic imbalance and impaired baroreflex function have been implicated as the main cause of this pathophysiology. The nucleus tractus solitarii (NTS) is a critical central region for autonomic control and integration of baroreflex function, and utilizes glutamate as its primary excitatory neurotransmitter. It was demonstrated that plasticity in glutamatergic synaptic transmission in the NTS contribute to several cardiovascular dysfunctions. To study the possible central mechanisms involved in these alterations, we have used the Hindlimb-Unloaded (HU) rat, a well-established model of CVD in rodents. The goal of the present proposal is to determine the effects of HU on glutamatergic neurotransmission and the intrinsic properties of NTS neurons. I hypothesize that CVD following HU increases excitatory modulation of NTS neurons within the baroreflex pathways. To test this hypothesis, my specific aims are to determine: 1) The extent to which CVD/HU increases afferent glutamate release via presynaptic mechanisms; 2) The contribution of ionotropic and metabotropic glutamate receptors on excitatory neurotransmission after CVD; and 3) whether the plasticity in synaptic neurotransmission are associated with morphological changes in NTS neurons of HU rats. These aims will be accomplished via multiple synergistic approaches, including electrophysiology and live fluorescent imaging in nTS slices, and molecular biology techniques. Together, these studies will determine the underlying contribution of the NTS and their mechanisms, which may serve to increase our understanding of CVD and potential therapies.