Mechanisms Underlying Neuroplasticity in the Nucleus Tractus Solitarii Following Hindlimb Unloading in Rats. (21st November 2020)

• Record Type: Journal Article
• Authors: Lima-Silveira, Ludmila; Martinez, Diana; Hasser, Eileen M.; Kline, David D.
• Is Part Of: Neuroscience. Volume 449(2020)
• Page Start: 214
• Page End: 227
• Publication Date: 2020-11-21
• Subjects: AP action potential -- CVD cardiovascular deconditioning -- HU hindlimb unloading -- nTS nucleus tractus solitarii -- RMP resting membrane potential; glutamate -- GABA -- autonomic nervous system -- cardiovascular deconditioning; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2020.09.043
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Hindlimb unloading (HU) in rats enhanced glutamatergic signaling to nTS neurons Presynaptic calcium signaling is augmented after HU HU increased the contribution of postsynaptic NMDARs By contrast, HU reduced neuronal excitability by increasing GABAergic modulation Abstract: Hindlimb unloading (HU) in rats induces cardiovascular deconditioning (CVD) analogous to that observed in individuals exposed to microgravity or bed rest. Among other physiological changes, HU rats exhibit autonomic imbalance and altered baroreflex function. Lack of change in visceral afferent activity that projects to the brainstem in HU rats suggests that neuronal plasticity within central nuclei processing cardiovascular afferents may be responsible for these changes in CVD and HU. The nucleus tractus solitarii (nTS) is a critical brainstem region for autonomic control and integration of cardiovascular reflexes. In this study, we used patch electrophysiology, live-cell calcium imaging and molecular methods to investigate the effects of HU on glutamatergic synaptic transmission and intrinsic properties of nTS neurons. HU increased the amplitude of monosynaptic excitatory postsynaptic currents and presynaptic calcium entry evoked by afferent tractus solitarii stimulus (TS-EPSC); spontaneous (s) EPSCs were unaffected. The addition of a NMDA receptor antagonist (AP5) reduced TS-EPSC amplitude and sEPSC frequency in HU but not control. Despite the increase in glutamatergic inputs, HU neurons were more hyperpolarized and exhibited intrinsic decreased excitability compared to controls. After block of ionotropic glutamatergic and GABAergic synaptic transmission (NBQX, AP5, Gabazine), HU neuronal membrane potential depolarized and neuronal excitability was comparable to controls. These data demonstrate that HU increases presynaptic release and TS-EPSC amplitude, which includes a NMDA receptor component. Furthermore, the decreased excitability and hyperpolarized membrane after HU are associated with enhanced GABAergic modulation. This functional neuroplasticity in the nTS may underly the CVD induced by HU.