Astrocytes as histaminergic gatekeepers of anxiety: A new pathway for emotional control

The mammalian brain harbors a remarkable variety of neuromodulatory systems that continuously adapt behavior to environmental demands. The histaminergic system— originating from the tuberomammillary nucleus of the hypothalamus—has long been recognized for its roles in arousal, attention and cognition. However, the contribution of the histaminergic system to anxiety has remained puzzling. Conventional wisdom is that anxiety is predominantly regulated by serotonergic neuromodulatory input provided by the dorsal and median raphe nuclei. But pharmacological and genetic manipulations of histamine signaling can also produce both anxiogenic and anxiolytic outcomes. In a paper recently published in Neuron, Li and colleagues have clarified the role of histamine by discovering that histamine released in the ventral CA1 region of the hippocampus suppresses anxiety-like behavior. Further, they show that histamine suppresses anxiety-like behavior by triggering a calcium-dependent release of GABA from astrocytes, rather than neurons. This discovery advances our understanding of how a classic neuromodulator operates and places astrocytes at the center of a dedicated anxiolytic mechanism.