The mammalian retina is considered an autonomous neuronal tissue, yet there is evidence that it receives inputs from the brain in the form of retinopetal axons. A sub-population of these axons was suggested to belong to histaminergic neurons located in the tuberomammillarynucleus (TMN) of the hypothalamus. Using viral injections to the TMN, we identified these retinopetal axons and found that although few in number, they extensively branch to cover a large portion of the retina. Using Ca2+ imaging and electrophysiology, we show that histamine application increases spontaneous firing rates and alters the light responses of a significant portion of retinal ganglion cells (RGCs). Direct activation of the histaminergic axons also induced significant changes in RGCs activity. Since activity in the TMN was shown to correlate with arousal state, our data suggest the retinal code may change with the animal's behavioral state through the release of histamine from TMN histaminergic neurons.