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Phase shifting capacity of the circadian pacemaker determined by the SCN neuronal network organization.

vanderLeest HT, Rohling JH, Michel S, Meijer JH - PLoS ONE (2009)

Bottom Line: The effects of light on the circadian system are strongly dependent on the photoperiod to which animals are exposed.Application of N-methyl-D-aspartate (NMDA) induced sustained increments in electrical activity that were not significantly different in the slices from long and short photoperiods.We conclude that the photoperiodic dependent phase responses are determined by the SCN and propose that synchronization among SCN neurons enhances the phase shifting capacity of the circadian system.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Cell Biology, Laboratory for Neurophysiology, Leiden University Medical Center, Leiden, The Netherlands.

ABSTRACT

Background: In mammals, a major circadian pacemaker that drives daily rhythms is located in the suprachiasmatic nuclei (SCN), at the base of the hypothalamus. The SCN receive direct light input via the retino-hypothalamic tract. Light during the early night induces phase delays of circadian rhythms while during the late night it leads to phase advances. The effects of light on the circadian system are strongly dependent on the photoperiod to which animals are exposed. An explanation for this phenomenon is currently lacking.

Methodology and principal findings: We recorded running wheel activity in C57 mice and observed large amplitude phase shifts in short photoperiods and small shifts in long photoperiods. We investigated whether these different light responses under short and long days are expressed within the SCN by electrophysiological recordings of electrical impulse frequency in SCN slices. Application of N-methyl-D-aspartate (NMDA) induced sustained increments in electrical activity that were not significantly different in the slices from long and short photoperiods. These responses led to large phase shifts in slices from short days and small phase shifts in slices from long days. An analysis of neuronal subpopulation activity revealed that in short days the amplitude of the rhythm was larger than in long days.

Conclusions: The data indicate that the photoperiodic dependent phase responses are intrinsic to the SCN. In contrast to earlier predictions from limit cycle theory, we observed large phase shifting responses in high amplitude rhythms in slices from short days, and small shifts in low amplitude rhythms in slices from long days. We conclude that the photoperiodic dependent phase responses are determined by the SCN and propose that synchronization among SCN neurons enhances the phase shifting capacity of the circadian system.

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Phase shifts of multiunit electrical activity rhythms in brain slices from mice kept on a short and long photoperiod.Examples of extracellular multiunit recordings from the SCN in mice kept on a short photoperiod (A, C) and on a long photoperiod (B, D). Action potentials were counted in 10 s bins, and are plotted as a function of circadian time, determined by activity onsets from the mice prior to slice preparation. NMDA pulses were given 3 hours after the activity onset (CT 15), on the first cycle in vitro, in slices from both short (C) and long (D) day animals. In slices obtained from short day animals these pulses induced a delay in the peak time of the rhythm on the day following the application. Peak times are indicated by a vertical line. (E) Delays obtained at CT 15 from short day animals were significantly larger than delays obtained from long day animals. The magnitude of the delay after an NMDA pulse at CT 15 was significantly different between day lengths (p<0.01). (F) The magnitude of the behavioral delay was not different from the delay observed in vitro, for both day lengths (short day in vitro vs. behavior p>0.3, long day in vitro vs. behavior, p>0.4).
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pone-0004976-g002: Phase shifts of multiunit electrical activity rhythms in brain slices from mice kept on a short and long photoperiod.Examples of extracellular multiunit recordings from the SCN in mice kept on a short photoperiod (A, C) and on a long photoperiod (B, D). Action potentials were counted in 10 s bins, and are plotted as a function of circadian time, determined by activity onsets from the mice prior to slice preparation. NMDA pulses were given 3 hours after the activity onset (CT 15), on the first cycle in vitro, in slices from both short (C) and long (D) day animals. In slices obtained from short day animals these pulses induced a delay in the peak time of the rhythm on the day following the application. Peak times are indicated by a vertical line. (E) Delays obtained at CT 15 from short day animals were significantly larger than delays obtained from long day animals. The magnitude of the delay after an NMDA pulse at CT 15 was significantly different between day lengths (p<0.01). (F) The magnitude of the behavioral delay was not different from the delay observed in vitro, for both day lengths (short day in vitro vs. behavior p>0.3, long day in vitro vs. behavior, p>0.4).

Mentions: To investigate whether the difference in the magnitude of the phase shift in long and short days is retained in the SCN in vitro we kept animals under long and short day length and prepared hypothalamic slices containing the SCN on the third day after release in constant darkness (Figure 2). We recorded electrical impulse frequency in the SCN by stationary electrodes and applied NMDA pulses (10 µM, 30 min duration) by switching from regular artificial cerebrospinal fluid (ACSF) to NMDA containing ACSF. The NMDA receptor is of crucial importance in mediating phase shifting by light and application of the glutamate receptor agonist NMDA to brain slices in vitro generates phase shifts of the circadian rhythm resembling photic phase responses [19]–[21]. The timing of the NMDA pulse was based on the extrapolated behavioral activity of the animal before slice preparation, and was aimed 3 hours after activity onset, where the largest shifts in behavior were observed in both photoperiods.


Phase shifting capacity of the circadian pacemaker determined by the SCN neuronal network organization.

vanderLeest HT, Rohling JH, Michel S, Meijer JH - PLoS ONE (2009)

Phase shifts of multiunit electrical activity rhythms in brain slices from mice kept on a short and long photoperiod.Examples of extracellular multiunit recordings from the SCN in mice kept on a short photoperiod (A, C) and on a long photoperiod (B, D). Action potentials were counted in 10 s bins, and are plotted as a function of circadian time, determined by activity onsets from the mice prior to slice preparation. NMDA pulses were given 3 hours after the activity onset (CT 15), on the first cycle in vitro, in slices from both short (C) and long (D) day animals. In slices obtained from short day animals these pulses induced a delay in the peak time of the rhythm on the day following the application. Peak times are indicated by a vertical line. (E) Delays obtained at CT 15 from short day animals were significantly larger than delays obtained from long day animals. The magnitude of the delay after an NMDA pulse at CT 15 was significantly different between day lengths (p<0.01). (F) The magnitude of the behavioral delay was not different from the delay observed in vitro, for both day lengths (short day in vitro vs. behavior p>0.3, long day in vitro vs. behavior, p>0.4).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2655235&req=5

pone-0004976-g002: Phase shifts of multiunit electrical activity rhythms in brain slices from mice kept on a short and long photoperiod.Examples of extracellular multiunit recordings from the SCN in mice kept on a short photoperiod (A, C) and on a long photoperiod (B, D). Action potentials were counted in 10 s bins, and are plotted as a function of circadian time, determined by activity onsets from the mice prior to slice preparation. NMDA pulses were given 3 hours after the activity onset (CT 15), on the first cycle in vitro, in slices from both short (C) and long (D) day animals. In slices obtained from short day animals these pulses induced a delay in the peak time of the rhythm on the day following the application. Peak times are indicated by a vertical line. (E) Delays obtained at CT 15 from short day animals were significantly larger than delays obtained from long day animals. The magnitude of the delay after an NMDA pulse at CT 15 was significantly different between day lengths (p<0.01). (F) The magnitude of the behavioral delay was not different from the delay observed in vitro, for both day lengths (short day in vitro vs. behavior p>0.3, long day in vitro vs. behavior, p>0.4).
Mentions: To investigate whether the difference in the magnitude of the phase shift in long and short days is retained in the SCN in vitro we kept animals under long and short day length and prepared hypothalamic slices containing the SCN on the third day after release in constant darkness (Figure 2). We recorded electrical impulse frequency in the SCN by stationary electrodes and applied NMDA pulses (10 µM, 30 min duration) by switching from regular artificial cerebrospinal fluid (ACSF) to NMDA containing ACSF. The NMDA receptor is of crucial importance in mediating phase shifting by light and application of the glutamate receptor agonist NMDA to brain slices in vitro generates phase shifts of the circadian rhythm resembling photic phase responses [19]–[21]. The timing of the NMDA pulse was based on the extrapolated behavioral activity of the animal before slice preparation, and was aimed 3 hours after activity onset, where the largest shifts in behavior were observed in both photoperiods.

Bottom Line: The effects of light on the circadian system are strongly dependent on the photoperiod to which animals are exposed.Application of N-methyl-D-aspartate (NMDA) induced sustained increments in electrical activity that were not significantly different in the slices from long and short photoperiods.We conclude that the photoperiodic dependent phase responses are determined by the SCN and propose that synchronization among SCN neurons enhances the phase shifting capacity of the circadian system.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Cell Biology, Laboratory for Neurophysiology, Leiden University Medical Center, Leiden, The Netherlands.

ABSTRACT

Background: In mammals, a major circadian pacemaker that drives daily rhythms is located in the suprachiasmatic nuclei (SCN), at the base of the hypothalamus. The SCN receive direct light input via the retino-hypothalamic tract. Light during the early night induces phase delays of circadian rhythms while during the late night it leads to phase advances. The effects of light on the circadian system are strongly dependent on the photoperiod to which animals are exposed. An explanation for this phenomenon is currently lacking.

Methodology and principal findings: We recorded running wheel activity in C57 mice and observed large amplitude phase shifts in short photoperiods and small shifts in long photoperiods. We investigated whether these different light responses under short and long days are expressed within the SCN by electrophysiological recordings of electrical impulse frequency in SCN slices. Application of N-methyl-D-aspartate (NMDA) induced sustained increments in electrical activity that were not significantly different in the slices from long and short photoperiods. These responses led to large phase shifts in slices from short days and small phase shifts in slices from long days. An analysis of neuronal subpopulation activity revealed that in short days the amplitude of the rhythm was larger than in long days.

Conclusions: The data indicate that the photoperiodic dependent phase responses are intrinsic to the SCN. In contrast to earlier predictions from limit cycle theory, we observed large phase shifting responses in high amplitude rhythms in slices from short days, and small shifts in low amplitude rhythms in slices from long days. We conclude that the photoperiodic dependent phase responses are determined by the SCN and propose that synchronization among SCN neurons enhances the phase shifting capacity of the circadian system.

Show MeSH