The Circadian Clock Gene Connects the Molecular Clock to Neural Activity in the Suprachiasmatic Nucleus
The neural activity patterns of suprachiasmatic nucleus (SCN) neurons are dynamically regulated throughout the circadian cycle with highest levels of spontaneous action potentials during the day. These rhythms in electrical activity are critical for the function of the circadian timing system and ye...
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Online Access: | https://doi.org/10.1177/1759091415610761 |
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doaj-80e0ce94d19e4013b6857606148015f82020-11-25T03:43:17ZengSAGE PublishingASN Neuro1759-09142015-10-01710.1177/175909141561076110.1177_1759091415610761The Circadian Clock Gene Connects the Molecular Clock to Neural Activity in the Suprachiasmatic NucleusTakashi Kudo0Gene D. Block1Christopher S. Colwell2Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USADepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USADepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USAThe neural activity patterns of suprachiasmatic nucleus (SCN) neurons are dynamically regulated throughout the circadian cycle with highest levels of spontaneous action potentials during the day. These rhythms in electrical activity are critical for the function of the circadian timing system and yet the mechanisms by which the molecular clockwork drives changes in the membrane are not well understood. In this study, we sought to examine how the clock gene Period1 ( Per1 ) regulates the electrical activity in the mouse SCN by transiently and selectively decreasing levels of PER1 through use of an antisense oligodeoxynucleotide. We found that this treatment effectively reduced SCN neural activity. Direct current injection to restore the normal membrane potential partially, but not completely, returned firing rate to normal levels. The antisense treatment also reduced baseline [Ca 2+ ]i levels as measured by Fura2 imaging technique. Whole cell patch clamp recording techniques were used to examine which specific potassium currents were altered by the treatment. These recordings revealed that the large conductance [Ca 2+ ]i-activated potassium currents were reduced in antisense-treated neurons and that blocking this current mimicked the effects of the anti-sense on SCN firing rate. These results indicate that the circadian clock gene Per1 alters firing rate in SCN neurons and raise the possibility that the large conductance [Ca 2+ ]i-activated channel is one of the targets.https://doi.org/10.1177/1759091415610761 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Takashi Kudo Gene D. Block Christopher S. Colwell |
spellingShingle |
Takashi Kudo Gene D. Block Christopher S. Colwell The Circadian Clock Gene Connects the Molecular Clock to Neural Activity in the Suprachiasmatic Nucleus ASN Neuro |
author_facet |
Takashi Kudo Gene D. Block Christopher S. Colwell |
author_sort |
Takashi Kudo |
title |
The Circadian Clock Gene Connects the Molecular Clock to Neural Activity in the Suprachiasmatic Nucleus |
title_short |
The Circadian Clock Gene Connects the Molecular Clock to Neural Activity in the Suprachiasmatic Nucleus |
title_full |
The Circadian Clock Gene Connects the Molecular Clock to Neural Activity in the Suprachiasmatic Nucleus |
title_fullStr |
The Circadian Clock Gene Connects the Molecular Clock to Neural Activity in the Suprachiasmatic Nucleus |
title_full_unstemmed |
The Circadian Clock Gene Connects the Molecular Clock to Neural Activity in the Suprachiasmatic Nucleus |
title_sort |
circadian clock gene connects the molecular clock to neural activity in the suprachiasmatic nucleus |
publisher |
SAGE Publishing |
series |
ASN Neuro |
issn |
1759-0914 |
publishDate |
2015-10-01 |
description |
The neural activity patterns of suprachiasmatic nucleus (SCN) neurons are dynamically regulated throughout the circadian cycle with highest levels of spontaneous action potentials during the day. These rhythms in electrical activity are critical for the function of the circadian timing system and yet the mechanisms by which the molecular clockwork drives changes in the membrane are not well understood. In this study, we sought to examine how the clock gene Period1 ( Per1 ) regulates the electrical activity in the mouse SCN by transiently and selectively decreasing levels of PER1 through use of an antisense oligodeoxynucleotide. We found that this treatment effectively reduced SCN neural activity. Direct current injection to restore the normal membrane potential partially, but not completely, returned firing rate to normal levels. The antisense treatment also reduced baseline [Ca 2+ ]i levels as measured by Fura2 imaging technique. Whole cell patch clamp recording techniques were used to examine which specific potassium currents were altered by the treatment. These recordings revealed that the large conductance [Ca 2+ ]i-activated potassium currents were reduced in antisense-treated neurons and that blocking this current mimicked the effects of the anti-sense on SCN firing rate. These results indicate that the circadian clock gene Per1 alters firing rate in SCN neurons and raise the possibility that the large conductance [Ca 2+ ]i-activated channel is one of the targets. |
url |
https://doi.org/10.1177/1759091415610761 |
work_keys_str_mv |
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