Top-down modulation of the retinal code via histaminergic neurons of the hypothalamus.
Rebekah A WarwickSerena RiccitelliAlina S HeukampHadar YaakovBani Prasad SwainLea AnkriJonathan MayzelNoa GileadReut Parness-YossifonStefano Di MarcoMichal Rivlin-EtzionPublished in: Science advances (2024)
The mammalian retina is considered an autonomous circuit, yet work dating back to Ramon y Cajal indicates that it receives inputs from the brain. How such inputs affect retinal processing has remained unknown. We confirmed brain-to-retina projections of histaminergic neurons from the mouse hypothalamus. Histamine application ex vivo altered the activity of various retinal ganglion cells (RGCs), including direction-selective RGCs that gained responses to high motion velocities. These results were reproduced in vivo with optic tract recordings where histaminergic retinopetal axons were activated chemogenetically. Such changes could improve vision of fast-moving objects (e.g., while running), which fits with the known increased activity of histaminergic neurons during arousal. An antihistamine drug reduced optomotor responses to high-speed moving stimuli in freely moving mice. In humans, the same antihistamine nonuniformly modulated visual sensitivity across the visual field, indicating an evolutionary conserved function of the histaminergic system. Our findings expose a previously unappreciated role for brain-to-retina projections in modulating retinal function.
Keyphrases
- optic nerve
- diabetic retinopathy
- optical coherence tomography
- high speed
- resting state
- white matter
- spinal cord
- functional connectivity
- atomic force microscopy
- cerebral ischemia
- emergency department
- type diabetes
- transcription factor
- signaling pathway
- genome wide
- multiple sclerosis
- oxidative stress
- adipose tissue
- skeletal muscle
- metabolic syndrome
- endoplasmic reticulum stress
- insulin resistance
- spinal cord injury
- high fat diet induced
- dna methylation
- cell death