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A Path to Sleep Is through the Eye(1,2,3).

Morin LP - eNeuro (2015)

Bottom Line: The visual input route is a practical avenue to follow in pursuit of the neural circuitry and mechanisms governing sleep and arousal in small nocturnal mammals and the organizational principles may be similar in diurnal humans.Photosomnolence studies are likely to be particularly advantageous because the timing of sleep is largely under experimenter control.Moreover, the experimental designs and associated results benefit from a substantial amount of existing neuroanatomical and pharmacological literature that provides a solid framework guiding the conduct and interpretation of future investigations.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Psychiatry and Graduate Program in Neuroscience, Stony Brook Medicine, Stony Brook University , Stony Brook, New York 11794.

ABSTRACT
Light has long been known to modulate sleep, but recent discoveries support its use as an effective nocturnal stimulus for eliciting sleep in certain rodents. "Photosomnolence" is mediated by classical and ganglion cell photoreceptors and occurs despite the ongoing high levels of locomotion at the time of stimulus onset. Brief photic stimuli trigger rapid locomotor suppression, sleep, and a large drop in core body temperature (Tc; Phase 1), followed by a relatively fixed duration interval of sleep (Phase 2) and recovery (Phase 3) to pre-sleep activity levels. Additional light can lengthen Phase 2. Potential retinal pathways through which the sleep system might be light-activated are described and the potential roles of orexin (hypocretin) and melanin-concentrating hormone are discussed. The visual input route is a practical avenue to follow in pursuit of the neural circuitry and mechanisms governing sleep and arousal in small nocturnal mammals and the organizational principles may be similar in diurnal humans. Photosomnolence studies are likely to be particularly advantageous because the timing of sleep is largely under experimenter control. Sleep can now be effectively studied using uncomplicated, nonintrusive methods with behavior evaluation software tools; surgery for EEG electrode placement is avoidable. The research protocol for light-induced sleep is easily implemented and useful for assessing the effects of experimental manipulations on the sleep induction pathway. Moreover, the experimental designs and associated results benefit from a substantial amount of existing neuroanatomical and pharmacological literature that provides a solid framework guiding the conduct and interpretation of future investigations.

No MeSH data available.


Related in: MedlinePlus

Wheel running rate by non-photostimulated mice (CON; A); mice that received 10 light flashes, 2 ms each, with 30 s interflash intervals (IFI; B); and mice that received a single 5 min light pulse (C). Photic stimulation began at time 0. The filled squares/red dotted line indicates the behavior of mice lacking melanopsin (OPN4−/−). The rd/rd mice (open triangles/green dashed line) lack rods or cones. WT, Wild-type controls (filled circles/black solid line). In B and C, the OPN4−/− mice show a rapid locomotor suppression effect that is soon followed by erratic levels of locomotion, rather than the typical complete suppression seen in WT and rd/rd mice. After Figure 3 in Morin and Studholme (2011).
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Figure 2: Wheel running rate by non-photostimulated mice (CON; A); mice that received 10 light flashes, 2 ms each, with 30 s interflash intervals (IFI; B); and mice that received a single 5 min light pulse (C). Photic stimulation began at time 0. The filled squares/red dotted line indicates the behavior of mice lacking melanopsin (OPN4−/−). The rd/rd mice (open triangles/green dashed line) lack rods or cones. WT, Wild-type controls (filled circles/black solid line). In B and C, the OPN4−/− mice show a rapid locomotor suppression effect that is soon followed by erratic levels of locomotion, rather than the typical complete suppression seen in WT and rd/rd mice. After Figure 3 in Morin and Studholme (2011).

Mentions: Phase 1 occurs in mice lacking ipRGCs or classical rod/cone photoreceptors (Fig. 2; Morin and Studholme, 2011). However, the emergent locomotor suppression/photosomnolence pattern of the average mouse lacking ipRGCs is substantially different from that of wild-type or rodless/coneless mice. On the one hand, mice lacking ipRGCs exhibit robust short-term suppression during the initial 5 min after light onset. On the other hand, absence of ipRGCs prevents the typical, prolonged light-induced, locomotor suppression. The locomotion level remains erratically suppressed for the expected duration of Phase 2 (Fig. 2B,C). These observations suggest three things: (1) Phase 1 can be triggered by either ipRGC or classical photoreceptors; (2) the duration of Phase 2 is normal if only the classical photoreceptors are absent and is more or less normal if only the ipRGCs are absent; and (3) light is a much less effective locomotion suppressor (or sleep inducer) in mice lacking only ipRGCs. The last point may indicate that differing mechanisms control the different portions of the locomotor suppression pattern (onset, duration, recovery) and the ability of the sleep induction system to be activated by light. The photosomnolence data, as indicated by behavioral sleep indices (Morin and Studholme, 2011), are consistent with additional information showing that ipRGCs are not necessary for the initiation of normal light-induced sleep as estimated from wheel running results (Mrosovsky and Hattar, 2003) or measured by EEG (Altimus et al., 2008; Lupi et al., 2008; Tsai et al., 2009; Muindi et al., 2013), but are necessary for the normal maintenance of such. In addition to the foregoing, it should be noted that only about two-thirds of mice lacking melanopsin fail to show photosomnolence; responses by the remaining third are seemingly normal (Morin and Studholme, 2011).


A Path to Sleep Is through the Eye(1,2,3).

Morin LP - eNeuro (2015)

Wheel running rate by non-photostimulated mice (CON; A); mice that received 10 light flashes, 2 ms each, with 30 s interflash intervals (IFI; B); and mice that received a single 5 min light pulse (C). Photic stimulation began at time 0. The filled squares/red dotted line indicates the behavior of mice lacking melanopsin (OPN4−/−). The rd/rd mice (open triangles/green dashed line) lack rods or cones. WT, Wild-type controls (filled circles/black solid line). In B and C, the OPN4−/− mice show a rapid locomotor suppression effect that is soon followed by erratic levels of locomotion, rather than the typical complete suppression seen in WT and rd/rd mice. After Figure 3 in Morin and Studholme (2011).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4596090&req=5

Figure 2: Wheel running rate by non-photostimulated mice (CON; A); mice that received 10 light flashes, 2 ms each, with 30 s interflash intervals (IFI; B); and mice that received a single 5 min light pulse (C). Photic stimulation began at time 0. The filled squares/red dotted line indicates the behavior of mice lacking melanopsin (OPN4−/−). The rd/rd mice (open triangles/green dashed line) lack rods or cones. WT, Wild-type controls (filled circles/black solid line). In B and C, the OPN4−/− mice show a rapid locomotor suppression effect that is soon followed by erratic levels of locomotion, rather than the typical complete suppression seen in WT and rd/rd mice. After Figure 3 in Morin and Studholme (2011).
Mentions: Phase 1 occurs in mice lacking ipRGCs or classical rod/cone photoreceptors (Fig. 2; Morin and Studholme, 2011). However, the emergent locomotor suppression/photosomnolence pattern of the average mouse lacking ipRGCs is substantially different from that of wild-type or rodless/coneless mice. On the one hand, mice lacking ipRGCs exhibit robust short-term suppression during the initial 5 min after light onset. On the other hand, absence of ipRGCs prevents the typical, prolonged light-induced, locomotor suppression. The locomotion level remains erratically suppressed for the expected duration of Phase 2 (Fig. 2B,C). These observations suggest three things: (1) Phase 1 can be triggered by either ipRGC or classical photoreceptors; (2) the duration of Phase 2 is normal if only the classical photoreceptors are absent and is more or less normal if only the ipRGCs are absent; and (3) light is a much less effective locomotion suppressor (or sleep inducer) in mice lacking only ipRGCs. The last point may indicate that differing mechanisms control the different portions of the locomotor suppression pattern (onset, duration, recovery) and the ability of the sleep induction system to be activated by light. The photosomnolence data, as indicated by behavioral sleep indices (Morin and Studholme, 2011), are consistent with additional information showing that ipRGCs are not necessary for the initiation of normal light-induced sleep as estimated from wheel running results (Mrosovsky and Hattar, 2003) or measured by EEG (Altimus et al., 2008; Lupi et al., 2008; Tsai et al., 2009; Muindi et al., 2013), but are necessary for the normal maintenance of such. In addition to the foregoing, it should be noted that only about two-thirds of mice lacking melanopsin fail to show photosomnolence; responses by the remaining third are seemingly normal (Morin and Studholme, 2011).

Bottom Line: The visual input route is a practical avenue to follow in pursuit of the neural circuitry and mechanisms governing sleep and arousal in small nocturnal mammals and the organizational principles may be similar in diurnal humans.Photosomnolence studies are likely to be particularly advantageous because the timing of sleep is largely under experimenter control.Moreover, the experimental designs and associated results benefit from a substantial amount of existing neuroanatomical and pharmacological literature that provides a solid framework guiding the conduct and interpretation of future investigations.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Psychiatry and Graduate Program in Neuroscience, Stony Brook Medicine, Stony Brook University , Stony Brook, New York 11794.

ABSTRACT
Light has long been known to modulate sleep, but recent discoveries support its use as an effective nocturnal stimulus for eliciting sleep in certain rodents. "Photosomnolence" is mediated by classical and ganglion cell photoreceptors and occurs despite the ongoing high levels of locomotion at the time of stimulus onset. Brief photic stimuli trigger rapid locomotor suppression, sleep, and a large drop in core body temperature (Tc; Phase 1), followed by a relatively fixed duration interval of sleep (Phase 2) and recovery (Phase 3) to pre-sleep activity levels. Additional light can lengthen Phase 2. Potential retinal pathways through which the sleep system might be light-activated are described and the potential roles of orexin (hypocretin) and melanin-concentrating hormone are discussed. The visual input route is a practical avenue to follow in pursuit of the neural circuitry and mechanisms governing sleep and arousal in small nocturnal mammals and the organizational principles may be similar in diurnal humans. Photosomnolence studies are likely to be particularly advantageous because the timing of sleep is largely under experimenter control. Sleep can now be effectively studied using uncomplicated, nonintrusive methods with behavior evaluation software tools; surgery for EEG electrode placement is avoidable. The research protocol for light-induced sleep is easily implemented and useful for assessing the effects of experimental manipulations on the sleep induction pathway. Moreover, the experimental designs and associated results benefit from a substantial amount of existing neuroanatomical and pharmacological literature that provides a solid framework guiding the conduct and interpretation of future investigations.

No MeSH data available.


Related in: MedlinePlus