TY - JOUR
T1 - Circadian rhythm of redox state regulates membrane excitability in hippocampal CA1 neurons
AU - Naseri Kouzehgarani, Ghazal
AU - Bothwell, Mia Y.
AU - Gillette, Martha U.
N1 - Funding Information:
National Science Foundation, Division of Graduate Education, Grant/Award Number: IGERT CMMB 0965918; Medical Scholars Program, University of Illinois; National Science Foundation, Division of Chemical, Bioengineering, Environmental, and Transport Systems, Grant/Award Number: STC EBICS 0939511; National Science Foundation, Division of Integrative Organismal Systems, Grant/Award Number: IOS 1354913; Beckman Institute Graduate Fellows Program, University of Illinois; National Institute of Mental Health, Grant/ Award Number: MH 109062
Funding Information:
The authors thank Jennifer W. Mitchell for assistance in brain slice preparation, insight on figure preparation, and review of the manuscript, and Ann C. Benefiel for help with manuscript submission. We acknowledge Kathleen Louis of Michigan State University for assistance with acquiring images used in Figure?a,b. We also thank Ian Bothwell, University of Illinois, for assistance with the graphical abstract. This study was supported by funding from the Beckman Institute Graduate Fellows Program at the University of Illinois, the Medical Scholars Program at the University of Illinois, the National Institutes of Health (U01 MH 109062), and the National Science Foundation (IGERT CMMB 0965918, CBET STC 0939511, and IOS 1354913). These sources of funding had no involvement in the study design, data collection, analysis, and interpretation, writing of the report, or in the decision to submit the paper for publication. This work was conducted in part at the Beckman Institute for Advanced Science and Technology at the University of Illinois at Urbana-Champaign.
Funding Information:
The authors thank Jennifer W. Mitchell for assistance in brain slice preparation, insight on figure preparation, and review of the manuscript, and Ann C. Benefiel for help with manuscript submission. We acknowledge Kathleen Louis of Michigan State University for assistance with acquiring images used in Figure 3a,b. We also thank Ian Bothwell, University of Illinois, for assistance with the graphical abstract. This study was supported by funding from the Beckman Institute Graduate Fellows Program at the University of Illinois, the Medical Scholars Program at the University of Illinois, the National Institutes of Health (U01 MH 109062), and the National Science Foundation (IGERT CMMB 0965918, CBET STC 0939511, and IOS 1354913). These sources of funding had no involvement in the study design, data collection, analysis, and interpretation, writing of the report, or in the decision to submit the paper for publication. This work was conducted in part at the Beckman Institute for Advanced Science and Technology at the University of Illinois at Urbana‐Champaign.
Publisher Copyright:
© 2019 Federation of European Neuroscience Societies and John Wiley & Sons Ltd
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Behaviors, such as sleeping, foraging, and learning, are controlled by different regions of the rat brain, yet they occur rhythmically over the course of day and night. They are aligned adaptively with the day-night cycle by an endogenous circadian clock in the suprachiasmatic nucleus (SCN), but local mechanisms of rhythmic control are not established. The SCN expresses a ~24-hr oscillation in reduction-oxidation that modulates its own neuronal excitability. Could circadian redox oscillations control neuronal excitability elsewhere in the brain? We focused on the CA1 region of the rat hippocampus, which is known for integrating information as memories and where clock gene expression undergoes a circadian oscillation that is in anti-phase to the SCN. Evaluating long-term imaging of endogenous redox couples and biochemical determination of glutathiolation levels, we observed oscillations with a ~24 hr period that is 180° out-of-phase to the SCN. Excitability of CA1 pyramidal neurons, primary hippocampal projection neurons, also exhibits a rhythm in resting membrane potential that is circadian time-dependent and opposite from that of the SCN. The reducing reagent glutathione rapidly and reversibly depolarized the resting membrane potential of CA1 neurons; the magnitude is time-of-day-dependent and, again, opposite from the SCN. These findings extend circadian redox regulation of neuronal excitability from the SCN to the hippocampus. Insights into this system contribute to understanding hippocampal circadian processes, such as learning and memory, seizure susceptibility, and memory loss with aging.
AB - Behaviors, such as sleeping, foraging, and learning, are controlled by different regions of the rat brain, yet they occur rhythmically over the course of day and night. They are aligned adaptively with the day-night cycle by an endogenous circadian clock in the suprachiasmatic nucleus (SCN), but local mechanisms of rhythmic control are not established. The SCN expresses a ~24-hr oscillation in reduction-oxidation that modulates its own neuronal excitability. Could circadian redox oscillations control neuronal excitability elsewhere in the brain? We focused on the CA1 region of the rat hippocampus, which is known for integrating information as memories and where clock gene expression undergoes a circadian oscillation that is in anti-phase to the SCN. Evaluating long-term imaging of endogenous redox couples and biochemical determination of glutathiolation levels, we observed oscillations with a ~24 hr period that is 180° out-of-phase to the SCN. Excitability of CA1 pyramidal neurons, primary hippocampal projection neurons, also exhibits a rhythm in resting membrane potential that is circadian time-dependent and opposite from that of the SCN. The reducing reagent glutathione rapidly and reversibly depolarized the resting membrane potential of CA1 neurons; the magnitude is time-of-day-dependent and, again, opposite from the SCN. These findings extend circadian redox regulation of neuronal excitability from the SCN to the hippocampus. Insights into this system contribute to understanding hippocampal circadian processes, such as learning and memory, seizure susceptibility, and memory loss with aging.
KW - CA1 pyramidal neurons
KW - circadian clock
KW - rat hippocampus
KW - reduction-oxidation
KW - suprachiasmatic nucleus
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U2 - 10.1111/ejn.14334
DO - 10.1111/ejn.14334
M3 - Article
C2 - 30614107
AN - SCOPUS:85060338008
SN - 0953-816X
VL - 51
SP - 34
EP - 46
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
IS - 1
ER -