Projections from subfornical organ to bed nucleus of the stria terminalis modulate inflammation-induced anxiety-like behaviors in mice

Peripheral inflammation is closely related to the pathogenesis of sickness behaviors and psychiatric disorders such as anxiety and depression. The circumventricular organs (CVOs) are important brain sites to perceive peripheral inflammatory signals, but few studies have reported their role in inflammation-induced anxiety or depression. Using a mouse model of lipopolysaccharide (LPS)-induced inflammation, we identified a previously unreported role of the subfornical organ (SFO), one of the CVOs, in combating inflammation-induced anxiety. LPS treatment induced anxiety-like and sickness behaviors in mice. Although both the SFO and the organum vasculosum of the lamina terminalis (a CVO) neurons were activated after LPS treatment, only manipulating SFO neurons modulated LPS-induced anxiety-like behaviors. Activating or inhibiting SFO neurons alleviated or aggravated LPS-induced anxiety-like behaviors. In addition, SFO exerted this effect through glutamatergic projections to the bed nucleus of the stria terminalis. Manipulating SFO neurons did not affect LPS-induced sickness behaviors. Thus, we uncovered an active role of SFO neurons in counteracting peripheral inflammation-induced anxiety.