A1609 Microglia regulate sympathetic PVN neuronal activity in both resting and hypertensive states

Abstract

Objectives: Hypertension is associated with chronic and low-grade neuroinflammation. Our previous studies show that microglia, the resident immune cells in the CNS, are activated in hypertension. Strikingly, loss of naïve or proinflammatory microglia oppositely regulates blood pressure in response to hypertension induction. In this study we are investigating the mechanism by which microglia influence RVLM-projecting PVN neuronal activity in resting and hypertensive state, respectively. Methods: Adult male transgenic CD11-DTR mice were randomly assigned into 4 groups: control, diphtheria toxin (DT; to deplete microglia), L-NAME (hypertensive induction), and L-NAME+DT. Sympathetic neurons in the hypothalamic PVN are retrograde labeled by microinjection of fluorescent microsphere into unilateral RVLM in the brain stem. The electronic profiles of RVLM-PVN neurons are recording in voltage clamp mode. Results: Depletion of naïve or proinflammatory microglia does not alter resting membrane potential or membrane resistance. However, loss of microglia significantly inhibits outward K current. The frequency and amplitude of spontaneous EPSC (sEPSC) and sIPSC are altered by removal of microglia. The overall power of naïve microglial depletion decreases excitatory input to RVLM-PVN neurons. Depletion of proinflammatory microglia in hypertensive mice decreases both excitatory and inhibitory inputs. Conclusion: Our results show that microglia are highly involved in shaping RVLM-PVN neuronal activity in both resting and hypertensive states.