LAUSR

The nucleus tractus solitarii (nTS) is the major integrative brainstem region for autonomic modulation and processing of cardiovascular reflexes. GABA and glutamate are the main inhibitory and excitatory neurotransmitters, respectively, within this nucleus. Alterations in the GABA-glutamate regulation in the nTS are related to numerous cardiovascular comorbidities. Bedridden individuals and people exposed to microgravity exhibit dysautonomia and cardiovascular deconditioning that are mimicked in the Hindlimb Unloading (HU) rat model. We have previously shown in the nTS HU increases glutamatergic neurotransmission yet decreases neuronal excitability. In this study, we investigated the effects of HU on nTS GABAergic neurotransmission. We hypothesized HU potentiates GABA signaling via increased GABAergic release and postsynaptic GABA receptor expression. Following HU or control postural exposure, GABAergic neurotransmission was assessed using whole-cell patch clamp while the magnitude of GABA release was evaluated via an intensity-based GABA sensing fluorescence reporter (iGABASnFR). In response to GABA interneuron stimulation the evoked inhibitory postsynaptic current (nTS-IPSC) amplitude and area, as well as iGABASnFR fluorescence, was greater in HU than control. HU also elevated the frequency but not amplitude of spontaneous miniature IPSCs. Picoapplication of GABA produced similar postsynaptic current responses in nTS neurons of HU and control. Moreover, HU did not alter GABAA receptor α1 subunit expression, indicating minimal alterations in postsynaptic membrane receptor expression. These results indicate that HU increases GABAergic signaling in the nTS likely via augmented release of GABA from presynaptic terminals. Altogether, our data indicate GABA plasticity contributes to the autonomic and cardiovascular alterations following CVD.