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Mice deficient of glutamatergic signaling from intrinsically photosensitive retinal ganglion cells exhibit abnormal circadian photoentrainment.

Purrier N, Engeland WC, Kofuji P - PLoS ONE (2014)

Bottom Line: The relative contribution of each neurotransmitter system for the circadian photoentrainment and other NIF visual responses is still unresolved.Other NIF responses such as the PLR and negative masking responses to light were also partially attenuated.Overall, these results suggest that glutamate from ipRGCs drives circadian photoentrainment and negative masking responses to light.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota, United States of America.

ABSTRACT
Several aspects of behavior and physiology, such as sleep and wakefulness, blood pressure, body temperature, and hormone secretion exhibit daily oscillations known as circadian rhythms. These circadian rhythms are orchestrated by an intrinsic biological clock in the suprachiasmatic nuclei (SCN) of the hypothalamus which is adjusted to the daily environmental cycles of day and night by the process of photoentrainment. In mammals, the neuronal signal for photoentrainment arises from a small subset of intrinsically photosensitive retinal ganglion cells (ipRGCs) that send a direct projection to the SCN. ipRGCs also mediate other non-image-forming (NIF) visual responses such as negative masking of locomotor activity by light, and the pupillary light reflex (PLR) via co-release of neurotransmitters glutamate and pituitary adenylate cyclase-activating peptide (PACAP) from their synaptic terminals. The relative contribution of each neurotransmitter system for the circadian photoentrainment and other NIF visual responses is still unresolved. We investigated the role of glutamatergic neurotransmission for circadian photoentrainment and NIF behaviors by selective ablation of ipRGC glutamatergic synaptic transmission in mice. Mutant mice displayed delayed re-entrainment to a 6 h phase shift (advance or delay) in the light cycle and incomplete photoentrainment in a symmetrical skeleton photoperiod regimen (1 h light pulses between 11 h dark periods). Circadian rhythmicity in constant darkness also was reduced in some mutant mice. Other NIF responses such as the PLR and negative masking responses to light were also partially attenuated. Overall, these results suggest that glutamate from ipRGCs drives circadian photoentrainment and negative masking responses to light.

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Vglut2-cKO mice show impaired re-entrainment to phase shifts in the LD cycle.(A) Representative double-plotted actograms of mice subjected to 6 hr phase advance on days marked. Top bars indicate initial LD cycle; bottom bars below indicate shifted cycle. (B) Representative double-plotted actograms of mice subjected to 6 hr phase delay on days marked. Top bars indicate initial LD cycle; bottom bars below indicate shifted cycle. (C) Number of days required for reentrainment after the 6 hr phase advance or phase delay in control (n = 7) and Vglut2-cKO (n = 4) mice. Vglut2 mice showed delayed re-entrainment to either phase advances or phase delays in the LD cycles (** p<0.05)).
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pone-0111449-g003: Vglut2-cKO mice show impaired re-entrainment to phase shifts in the LD cycle.(A) Representative double-plotted actograms of mice subjected to 6 hr phase advance on days marked. Top bars indicate initial LD cycle; bottom bars below indicate shifted cycle. (B) Representative double-plotted actograms of mice subjected to 6 hr phase delay on days marked. Top bars indicate initial LD cycle; bottom bars below indicate shifted cycle. (C) Number of days required for reentrainment after the 6 hr phase advance or phase delay in control (n = 7) and Vglut2-cKO (n = 4) mice. Vglut2 mice showed delayed re-entrainment to either phase advances or phase delays in the LD cycles (** p<0.05)).

Mentions: The impairment in photoentrainment of the Vglut2-cKO mice also was reflected by difficulties in readjusting to a ‘jet lag’ light-dark cycle produced by 6 h advanced and delayed light onsets (Figure 3). In the control mice, this phase advance evoked a rapid shift of locomotor activity rhythms, which took 2.0±0.6 days (n = 7) to re-entrain to the new LD regimen (Figures. 3A and 3C). In contrast, in the Vglut2-cKO mice, the phase advance in light onset required 6.8±0.5 days (n = 4) for reentrainment. Similarly, slower reentrainment was observed for the Vglut2-cKO mice in response to a 6 h phase delay (Figures 3B and 3C).


Mice deficient of glutamatergic signaling from intrinsically photosensitive retinal ganglion cells exhibit abnormal circadian photoentrainment.

Purrier N, Engeland WC, Kofuji P - PLoS ONE (2014)

Vglut2-cKO mice show impaired re-entrainment to phase shifts in the LD cycle.(A) Representative double-plotted actograms of mice subjected to 6 hr phase advance on days marked. Top bars indicate initial LD cycle; bottom bars below indicate shifted cycle. (B) Representative double-plotted actograms of mice subjected to 6 hr phase delay on days marked. Top bars indicate initial LD cycle; bottom bars below indicate shifted cycle. (C) Number of days required for reentrainment after the 6 hr phase advance or phase delay in control (n = 7) and Vglut2-cKO (n = 4) mice. Vglut2 mice showed delayed re-entrainment to either phase advances or phase delays in the LD cycles (** p<0.05)).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4214747&req=5

pone-0111449-g003: Vglut2-cKO mice show impaired re-entrainment to phase shifts in the LD cycle.(A) Representative double-plotted actograms of mice subjected to 6 hr phase advance on days marked. Top bars indicate initial LD cycle; bottom bars below indicate shifted cycle. (B) Representative double-plotted actograms of mice subjected to 6 hr phase delay on days marked. Top bars indicate initial LD cycle; bottom bars below indicate shifted cycle. (C) Number of days required for reentrainment after the 6 hr phase advance or phase delay in control (n = 7) and Vglut2-cKO (n = 4) mice. Vglut2 mice showed delayed re-entrainment to either phase advances or phase delays in the LD cycles (** p<0.05)).
Mentions: The impairment in photoentrainment of the Vglut2-cKO mice also was reflected by difficulties in readjusting to a ‘jet lag’ light-dark cycle produced by 6 h advanced and delayed light onsets (Figure 3). In the control mice, this phase advance evoked a rapid shift of locomotor activity rhythms, which took 2.0±0.6 days (n = 7) to re-entrain to the new LD regimen (Figures. 3A and 3C). In contrast, in the Vglut2-cKO mice, the phase advance in light onset required 6.8±0.5 days (n = 4) for reentrainment. Similarly, slower reentrainment was observed for the Vglut2-cKO mice in response to a 6 h phase delay (Figures 3B and 3C).

Bottom Line: The relative contribution of each neurotransmitter system for the circadian photoentrainment and other NIF visual responses is still unresolved.Other NIF responses such as the PLR and negative masking responses to light were also partially attenuated.Overall, these results suggest that glutamate from ipRGCs drives circadian photoentrainment and negative masking responses to light.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota, United States of America.

ABSTRACT
Several aspects of behavior and physiology, such as sleep and wakefulness, blood pressure, body temperature, and hormone secretion exhibit daily oscillations known as circadian rhythms. These circadian rhythms are orchestrated by an intrinsic biological clock in the suprachiasmatic nuclei (SCN) of the hypothalamus which is adjusted to the daily environmental cycles of day and night by the process of photoentrainment. In mammals, the neuronal signal for photoentrainment arises from a small subset of intrinsically photosensitive retinal ganglion cells (ipRGCs) that send a direct projection to the SCN. ipRGCs also mediate other non-image-forming (NIF) visual responses such as negative masking of locomotor activity by light, and the pupillary light reflex (PLR) via co-release of neurotransmitters glutamate and pituitary adenylate cyclase-activating peptide (PACAP) from their synaptic terminals. The relative contribution of each neurotransmitter system for the circadian photoentrainment and other NIF visual responses is still unresolved. We investigated the role of glutamatergic neurotransmission for circadian photoentrainment and NIF behaviors by selective ablation of ipRGC glutamatergic synaptic transmission in mice. Mutant mice displayed delayed re-entrainment to a 6 h phase shift (advance or delay) in the light cycle and incomplete photoentrainment in a symmetrical skeleton photoperiod regimen (1 h light pulses between 11 h dark periods). Circadian rhythmicity in constant darkness also was reduced in some mutant mice. Other NIF responses such as the PLR and negative masking responses to light were also partially attenuated. Overall, these results suggest that glutamate from ipRGCs drives circadian photoentrainment and negative masking responses to light.

Show MeSH
Related in: MedlinePlus