Histamine, an endogenous short-acting biogenic amine, is synthesized in several cell types of peripheral and central tissues and possesses a wide spectrum of activities, including its function in neurotransmission.
1 Although histamine has been one of the most studied and therapeutically exploited substances in medicine for a century, its strong association with the pluripotent mast cell and the atopic diseases seems to have deterred the investigation of its (patho)physiological role in other systems. Its presence in the brain was first shown more than 60 years ago, but research into its significance in the central nervous system has been delayed for many decades and still awaits elucidation.
2,3 Brain histamine is synthesized in neurons of the tuberomammillary nucleus of the posterior hypothalamus, which provides broad projections to most regions of the mammalian brain, including the visual cortex.
4 Acting on the four known types of histamine receptors—designated as H
1R, H
2R, H
3R, and H
4R—histamine is commonly implicated in basic homeostatic and brain functions, including sleep-wake regulation, circadian and feeding rhythms, body temperature, locomotor activity, learning and memory, and recently, neuroinflammation.
1,4,5
In the visual system, histamine is localized in the retina, optic nerve, and choroid layer.
6 Projections from the posterior hypothalamus descending to the optic chiasm and forming the retinopetal axons communicate through the optic nerve with dopaminergic amacrine cells in the rat and primate retina.
3,7 Retinopetal axons have been suggested to play a role in light adaptation through histamine receptors in the retina.
2,7,8 Following the visual information, histamine was reported to influence the neocortical synaptic plasticity in vivo, while cortical histaminergic activation increases the degree of plasticity in the mature thalamocortical communication suggesting that the central histaminergic system plays an important role in regulating synaptic plasticity.
9
Until now, no studies have exposed the effect of environmental stimuli on the histaminergic circuit of the brain pertaining to the visual system.
10,11 The effects of environmental enrichment vary from cellular and molecular to behavioral changes. In particular, studies have shown that enrichment increases the dendritic branches and length,
12,13 as well as the number of dendritic spines and the size of spines in some neuronal populations.
14–17 Differential housing also showed that the enriched environment increased cortical weight and thickness.
18 In addition, an enriched environment increases hippocampal neurogenesis leading the integration of newly born cells to functional neuronal circuits.
19,20 As far as the visual system is concerned, enrichment plays a beneficial role in the development of the retina through brain-derived neurotrophic factor, an effect which is more evident when combined with maternal enrichment.
21,22 Moreover, enrichment has been reported to increase plasticity in the adult visual cortex.
23
Despite the sporadic reports of the histaminergic influence on the visual system, the role of histamine in its development as well as any related sex differences have not been explored to date. This study provides first demonstration of histamine involvement in the postnatal development and adaptive response of the visual system in mammals.