A circadian rhythm-gated subcortical pathway for nighttime-light-induced depressive-like behaviors in mice

An, Kai Nan; Zhao, Huan; Miao, Yanli; Xu, Qi; Li, Yufei; Ma, Yinfa; Shi, Yi-Ming; Shen, Jiawei; Meng, Jianjun; Yao, Yong‐Gang; Zhang, Zhi; Chen, Ju-Tao; Bao, Jin; Zhang, Mei; Xue, Tian

doi:10.1038/s41593-020-0640-8

Cited by 115 publications

(110 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The non-visual effects of light are not only mediated via the SCN but also other brain structures [9,[14][15][16]. However, this area of research has not been covered sufficiently from the point of light pollution, even though it can play an important role in mediating the negative effects of LL and dLAN on physiology.…”

Section: Discussionmentioning

confidence: 99%

“…Light mediates its non-visual effects via the SCN but can also directly affect different brain structures, which regulate certain physiological functions. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells transmit information on lighting conditions directly to different brain areas, such as intergeniculate leaflet, the lateral geniculate nucleus of the thalamus [9,14,15], habenular nucleus, nucleus accumbens [9,15,16], medial amygdala, lateral hypothalamus and ventral preoptic area [9,15]. These structures can modulate sleep, mood and cognitive functions, heart rate and glucocorticoid levels [17].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Differential Effects of Constant Light and Dim Light at Night on the Circadian Control of Metabolism and Behavior

Rumanova

Okuliarova

Zeman

2020

IJMS

View full text Add to dashboard Cite

The disruption of circadian rhythms by environmental conditions can induce alterations in body homeostasis, from behavior to metabolism. The light:dark cycle is the most reliable environmental agent, which entrains circadian rhythms, although its credibility has decreased because of the extensive use of artificial light at night. Light pollution can compromise performance and health, but underlying mechanisms are not fully understood. The present review assesses the consequences induced by constant light (LL) in comparison with dim light at night (dLAN) on the circadian control of metabolism and behavior in rodents, since such an approach can identify the key mechanisms of chronodisruption. Data suggest that the effects of LL are more pronounced compared to dLAN and are directly related to the light level and duration of exposure. Dim LAN reduces nocturnal melatonin levels, similarly to LL, but the consequences on the rhythms of corticosterone and behavioral traits are not uniform and an improved quantification of the disrupted rhythms is needed. Metabolism is under strong circadian control and its disruption can lead to various pathologies. Moreover, metabolism is not only an output, but some metabolites and peripheral signal molecules can feedback on the circadian clockwork and either stabilize or amplify its desynchronization.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differential Effects of Constant Light and Dim Light at Night on the Circadian Control of Metabolism and Behavior

Rumanova

Okuliarova

Zeman

2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Nevertheless, the persistence and luxotonic nature of light-evoked responses in the human prefrontal cortex strongly suggest that it receives input from ipRGCs, just like the RTFC pathway in the mouse 31 . Moreover, mouse PHb neurons that receive input from ipRGCs have been shown to be mainly GABAergic 35 . This suggest that the mouse PHb transmits inhibitory drive to the prefrontal cortex, and might explain our observation that light exposure suppresses prefrontal activity.…”

Section: Discussionmentioning

confidence: 99%

“…This retino-thalamo-frontocortical (RTFC) pathway is completely separate, much smaller, and radically different from the main retino-thalamo-visuocortical (RTVC) pathway that targets the visual cortex through the dorsal division of the lateral geniculate nucleus (dLGN) and superior colliculus (SC). Note that the PHb has been shown to also project to the nucleus accumbens that modulates hedonic behaviors 35 .…”

Section: Introductionmentioning

confidence: 99%

Luxotonic signals in human prefrontal cortex as a possible substrate for effects of light on mood and cognition

Sabbah

Worden

Laniado

et al. 2020

Preprint

View full text Add to dashboard Cite

Light impacts mood and cognition of humans and other animals in ways we are only beginning to recognize. These effects are thought to depend upon a specialized retinal output signal arising from intrinsically photosensitive retinal ganglion cells (ipRGCs) that is being dedicated to a stable representation of the intensity of environmental light. Insights from animal studies now implicate a previously unknown pathway in the effects of environmental light on mood. A subset of ipRGCs transmits light-intensity information to the dorsothalamic perihabenular nucleus, which in turn, innervates the medial prefrontal cortex that plays a key role in mood regulation. While the prefrontal cortex has been implicated in depression and other mood disorders, its ability to encode the level of environmental light (luminance) has never been reported. Here, as a first step to probing for a similar retino-thalamo-frontocortical circuit in humans, we used functional magnetic resonance imaging (fMRI) to identify brain regions in which activity depended on luminance level where activity was modulated either transiently or persistently by light. Twelve brain regions altered their steady-state activity according to luminance level. Most were in the prefrontal cortex or in the classic thalamocortical visual pathway; others were found in the cerebellum, caudate, and pineal. Prefrontal cortex and pineal exhibited reduced BOLD signal in bright light, while the other centers exhibited increased BOLD signals. The light-evoked prefrontal response was affected by light history and closely resembled those of ipRGCs. Although we did not find clear correspondence between the luxotonic regions in humans and those in mice, the persistence and luxotonic nature of light-evoked responses in the human prefrontal cortex may suggest that it receives input from ipRGCs, just like in the mouse. We also found seventeen regions in which activity varied only transiently with luminance level. These regions, which are involved in visual processing, motor control, and cognition, were in the cerebral cortex, diverse subcortical structures, and cerebellum. Therefore, our results demonstrate the effects of light on diverse brain centers that contribute to motor control, cognition, emotion, and reward processing.

show abstract

“…Although serotypes other than AAV1 and AAV9 were not reported to drive trans‐synaptic Cre expression even at high titers (Zingg et al., 2017, 2020), we recommend using the lowest effective dose of AAV2‐retro to minimize the potential for off‐target labeling in bidirectional circuits. This approach has been used to study the role of lateral hypothalamus outputs to the periaqueductal gray in predation and evasion (Li et al., 2018), to study the role of locus coeruleus outputs to the spinal dorsal horn in acute and chronic itch (Koga et al., 2020), and to study the role of peri‐habenular nucleus outputs to the nucleus accumbens in depressive‐like behavior caused by light exposure at night (An et al., 2020).…”

Section: Intersectional Gene Expressionmentioning

confidence: 99%

Intersectional targeting of defined neural circuits by adeno‐associated virus vectors

Weinholtz

Castle

2020

J of Neuroscience Research

View full text Add to dashboard Cite

The mammalian nervous system is a complex network of interconnected cells. We review emerging techniques that use the axonal transport of adeno-associated virus (AAV) vectors to dissect neural circuits. These intersectional approaches specifically target AAV-mediated gene expression to discrete neuron populations based on their axonal connectivity, including: (a) neurons with one defined output, (b) neurons with one defined input, (c) neurons with one defined input and one defined output, and (d) neurons with two defined inputs or outputs. The number of labeled neurons can be directly controlled to trace axonal projections and examine cellular morphology. These approaches can precisely target the expression of fluorescent reporters, optogenetic ion channels, chemogenetic receptors, disease-associated proteins, and other factors to defined neural circuits in mammals ranging from mice to macaques, and thereby provide a powerful new means to understand the structure and function of the nervous system.

show abstract

A circadian rhythm-gated subcortical pathway for nighttime-light-induced depressive-like behaviors in mice

Cited by 115 publications

References 41 publications

Differential Effects of Constant Light and Dim Light at Night on the Circadian Control of Metabolism and Behavior

Differential Effects of Constant Light and Dim Light at Night on the Circadian Control of Metabolism and Behavior

Luxotonic signals in human prefrontal cortex as a possible substrate for effects of light on mood and cognition

Intersectional targeting of defined neural circuits by adeno‐associated virus vectors

Contact Info

Product

Resources

About