Biochemical controls: specialized retinal ganglion cells (Introduction)

by David Turell @, Sunday, January 29, 2023, 17:10 (501 days ago) @ David Turell

In macaque retina:

"Tiny pulses of electrochemical energy known as “spikes” underlie brain function, from sensation and cognition to engendering vigorous action or quiet reflection. But exactly what kind of messages do spikes transmit to, through, and from the brain? On page 376 of this issue, Liu et al. (1) show how spiking activity in a small set of neurons in the macaque monkey eye can inform the brain about the huge range of environmental illumination encountered across every 24-hour day-night cycle. Light detection by the eye can synchronize the body’s biological (or circadian) rhythms to this cycle, regulating essential functions such as sleep, attention, and energy expenditure. The authors found that unlike conventional photoreceptors (rods and cones, which show stereotyped responses across a limited range of background intensities), each time-of-day–detecting neuron signals a different range of photon flux, so that together the population can encode the vast intensity range from starlight to bright sunlight.


"Nerve signals serving the sense of sight are carried along the optic nerve to the brain on the extended processes of retinal output cells called ganglion cells. An important clue to understanding time-of-day coding came when a new ganglion cell type was identified in 2002 (6, 7). These ganglion cells, known as melanopsin cells, show intrinsic photosensitivity based on a melanopsin-initiated phototransduction cascade, and innervate brain centers that control circadian rhythms (6-10). Melanopsin belongs to a large family of light-sensitive opsins. In the eye, the best known are in rod and cone photoreceptors. By contrast, the melanopsin cells have many features in common with the rhabdomeric photoreceptors expressed in the eyes of invertebrates...They found that the monkey melanopsin cells have idiosyncratic irradiance response functions, with distinct cells showing activity peaks at different levels of absolute photon flux (called population-radiance encoding). Thus, the population of melanopsin cells work together to signal a larger range of intensity than can be covered by a single neuron rate code.

"Axonal recordings were previously used to show a similar population-coding mechanism in mouse retina (11). But the live immunotagging method developed by Liu et al. goes much further, allowing observations of phenomena such as multistable photoswitching in melanopsin cells. When rod and cone opsins absorb a photon, they fall into an inactive state, and the chromophore (light-absorbing molecule) 11-cis-retinal must pass through a multistep reactivation cascade involving transport out of, then back into, the photoreceptor. By contrast, the chromophore in melanopsin cells can be reversibly knocked into or out of active states by successive photon absorption. This and other features of melanopsin-based phototransduction extend the range of light intensity encoded by individual melanopsin cells.


"It is important to emphasize that the study by Liu et al. goes beyond simply reproducing in monkeys what has been previously found in mice. Mice and monkeys occupy distinct ecological and behavioral niches and, crucially, mice are primarily nocturnal whereas monkeys (and most humans) are primarily active during the day. This means that a common proximate mechanism (population-radiance encoding) drives distinct circadian behaviors, sending mice to hide and sleep at illumination levels where monkeys start to rise and begin their daily activity. Every physiological process in animal bodies undergoes circadian rhythms (13). The presence of common mechanisms for irradiance encoding across more than 70 million years of independent evolution indicates strong evolutionary pressure for tight control of circadian rhythms by accurate reporting of environmental illumination to the brain."

From the original article:

"Light regulates physiology, mood, and behavior through signals sent to the brain by intrinsically photosensitive retinal ganglion cells (ipRGCs). How primate ipRGCs sense light is unclear, as they are rare and challenging to target for electrophysiological recording. We developed a method of acute identification within the live, ex vivo retina. Using it, we found that ipRGCs of the macaque monkey are highly specialized to encode irradiance (the overall intensity of illumination) by blurring spatial, temporal, and chromatic features of the visual scene. We describe mechanisms at the molecular, cellular, and population scales that support irradiance encoding across orders-of-magnitude changes in light intensity. These mechanisms are conserved quantitatively across the ∼70 million years of evolution that separate macaques from mice."

Comment: time of day changes ambient light and affects our biological diurnal rhythms. These are specially designed neurons to fit a specific necessary function of adaptation.

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