Central histaminergic system reduces response gain and slows visual processing in the retina and lateral geniculate nucleus of awake mice

Sensory processing is dynamically modulated by an animals behavior and internal states. Growing evidence suggests that such modulation starts from early stages, already at the retina, but the underlying mechanisms remain elusive. Combining pharmacological and chemogenetic tools with single-unit extracellular recordings in awake head-fixed mice, here we identified that the visual responses of retinal ganglion cells and the lateral geniculate nucleus were both made weaker and slower by histaminergic projections from the tuberomammillary nucleus of the posterior hypothalamus. The observed changes in the visual responses were, however, not directly linked with histaminergic modulation of pupil dynamics or locomotion behavior. Instead, our computational modelling analysis suggests that the temporal response modulations arise from changes in the intrinsic properties of the circuit, such as gain modulation via the histamine H1 receptors in the retina. Facilitation of visual processing at low histamine levels may offer an ethological advantage, enabling animals to respond rapidly to visual threats during periods of reduced activity.