scholarly journals Daily electrical activity in the master circadian clock of a diurnal mammal

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Beatriz Bano-Otalora ◽  
Matthew J Moye ◽  
Timothy Brown ◽  
Robert J Lucas ◽  
Casey O Diekman ◽  
...  
Keyword(s):  
Mathematical Modeling ◽  
Data Assimilation ◽  
Electrical Activity ◽  
Ionic Mechanism ◽  
Suprachiasmatic Nuclei ◽  
Rhabdomys Pumilio ◽  
Primary Determinant ◽  
Ionic Mechanisms ◽  
Central Clock ◽  
Evoked Activity

Circadian rhythms in mammals are orchestrated by a central clock within the suprachiasmatic nuclei (SCN). Our understanding of the electrophysiological basis of SCN activity comes overwhelmingly from a small number of nocturnal rodent species, and the extent to which these are retained in day-active animals remains unclear. Here, we recorded the spontaneous and evoked electrical activity of single SCN neurons in the diurnal rodent Rhabdomys pumilio, and developed cutting-edge data assimilation and mathematical modeling approaches to uncover the underlying ionic mechanisms. As in nocturnal rodents, R. pumilio SCN neurons were more excited during daytime hours. By contrast, the evoked activity of R. pumilio neurons included a prominent suppressive response that is not present in the SCN of nocturnal rodents. Our modeling revealed and subsequent experiments confirmed transient subthreshold A-type potassium channels as the primary determinant of this response, and suggest a key role for this ionic mechanism in optimizing SCN function to accommodate R. pumilio’s diurnal niche.

scholarly journals Modeling the diversity of spontaneous and agonist-induced electrical activity in anterior pituitary corticotrophs

2017 ◽  
Vol 117 (6) ◽  
pp. 2298-2311 ◽  
Author(s):  
Patrick A. Fletcher ◽  
Hana Zemkova ◽  
Stanko S. Stojilkovic ◽  
Arthur Sherman
Keyword(s):  
Mathematical Modeling ◽  
Electrical Activity ◽  
Action Potentials ◽  
Hormone Secretion ◽  
Calcium Dependent ◽  
Electrophysiological Recordings ◽  
Electrophysiological Measurements ◽  
Ionic Mechanisms ◽  
Time Courses ◽  
Two Parameters

Pituitary corticotrophs fire action potentials spontaneously and in response to stimulation with corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP), and such electrical activity is critical for calcium signaling and calcium-dependent adrenocorticotropic hormone secretion. These cells typically fire tall, sharp action potentials when spontaneously active, but a variety of other spontaneous patterns have also been reported, including various modes of bursting. There is variability in reports of the fraction of corticotrophs that are electrically active, as well as their patterns of activity, and the sources of this variation are not well understood. The ionic mechanisms responsible for CRH- and AVP-triggered electrical activity in corticotrophs are also poorly characterized. We use electrophysiological measurements and mathematical modeling to investigate possible sources of variability in patterns of spontaneous and agonist-induced corticotroph electrical activity. In the model, variation in as few as two parameters can give rise to many of the types of patterns observed in electrophysiological recordings of corticotrophs. We compare the known mechanisms for CRH, AVP, and glucocorticoid actions and find that different ionic mechanisms can contribute in different but complementary ways to generate the complex time courses of CRH and AVP responses. In summary, our modeling suggests that corticotrophs have several mechanisms at their disposal to achieve their primary function of pacemaking depolarization and increased electrical activity in response to CRH and AVP. NEW & NOTEWORTHY We and others recently demonstrated that the electrical activity and calcium dynamics of corticotrophs are strikingly diverse, both spontaneously and in response to the agonists CRH and AVP. Here we demonstrate this diversity with electrophysiological measurements and use mathematical modeling to investigate its possible sources. We compare the known mechanisms of agonist-induced activity in the model, showing how the context of ionic conductances dictates the effects of agonists even when their target is fixed.

scholarly journals Daily electrical activity in the master circadian clock of a diurnal mammal

2020 ◽  
Author(s):  
Beatriz Bano-Otalora ◽  
Matthew J. Moye ◽  
Timothy M. Brown ◽  
Robert J. Lucas ◽  
Casey O. Diekman ◽  
...  
Keyword(s):  
Electrical Activity ◽  
Circadian Clock ◽  
Brain Slices ◽  
Computational Modelling ◽  
Membrane Properties ◽  
Murid Rodent ◽  
Rhabdomys Pumilio ◽  
Ionic Mechanisms ◽  
Modelling Approaches ◽  
Diurnal Mammal

AbstractDaily or circadian rhythms in mammals are orchestrated by a master circadian clock within the hypothalamic suprachiasmatic nuclei (SCN). Here, cell-autonomous oscillations in gene expression, intrinsic membrane properties, and synaptic communication shape the electrical landscape of the SCN across the circadian day, rendering SCN neurons overtly more active during the day than at night. This well-accepted hallmark bioelectrical feature of the SCN has overwhelmingly emerged from studies performed on a small number of nocturnal rodent species. Therefore, for the first time, we investigate the spontaneous and evoked electrical activity of SCN neurons in a diurnal mammal. To this end, we measured the electrical activity of individual SCN neurons during the day and at night in brain slices prepared from the diurnal murid rodent Rhabdomys pumilio and then developed cutting-edge data assimilation and mathematical modelling approaches to uncover the underlying ionic mechanisms. We find that R. pumilio SCN neurons were more excited in the day than at night, recapitulating the prototypical pattern of SCN neuronal activity previously observed in nocturnal rodents. By contrast, the evoked activity of R. pumilio neurons included a prominent suppressive response that is not present in the SCN of nocturnal rodents. Our computational modelling approaches reveal transient subthreshold A-type potassium channels as the primary determinant of the suppressive response and highlight a key role for this ionic mechanism in tuning excitability of clock neurons and optimising SCN function to accommodate R. pumilio’s diurnal niche.

Imaging the Human Brain with Magnetoencephalography

2011 ◽  
pp. 881-889
Author(s):  
Dimitrios Pantazis
Keyword(s):  
Mathematical Modeling ◽  
Medical Imaging ◽  
Magnetic Fields ◽  
Human Brain ◽  
Electrical Activity ◽  
Liquid Helium ◽  
Communication Networks ◽  
Brain Function ◽  
Imaging Modality ◽  
Neuronal Disorders

Magnetoencephalography is a relatively new medical imaging modality for the monitoring and imaging of human brain function. Extracranial magnetic fields produced by the working human brain are measured by extremely sensitive superconducting sensors, called SQUIDs, enclosed in a liquid helium-filled dewar. Mathematical modeling allows the formation of images or maps of cortical neuronal currents that reveal neural electrical activity, identify cortical communication networks, and facilitate the treatment of neuronal disorders, such as epilepsy.

Imaging the Human Brain with Magnetoencephalography

2011 ◽  
pp. 294-302
Author(s):  
Dimitrios Pantazis ◽  
Richard M. Leahy
Keyword(s):  
Mathematical Modeling ◽  
Medical Imaging ◽  
Magnetic Fields ◽  
Human Brain ◽  
Electrical Activity ◽  
Liquid Helium ◽  
Communication Networks ◽  
Brain Function ◽  
Imaging Modality ◽  
Neuronal Disorders

Magnetoencephalography is a relatively new medical imaging modality for the monitoring and imaging of human brain function. Extracranial magnetic fields produced by the working human brain are measured by extremely sensitive superconducting sensors, called SQUIDs, enclosed in a liquid helium-filled dewar. Mathematical modeling allows the formation of images or  maps of cortical neuronal currents that reveal neural electrical activity, identify cortical communication networks, and facilitate the treatment of neuronal disorders, such as epilepsy.

scholarly journals Minireview: The Circadian Clockwork of the Suprachiasmatic Nuclei—Analysis of a Cellular Oscillator that Drives Endocrine Rhythms

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 5624-5634 ◽  
Author(s):  
Elizabeth S. Maywood ◽  
John S. O’Neill ◽  
Johanna E. Chesham ◽  
Michael H. Hastings
Keyword(s):  
Neural Circuits ◽  
Clock Genes ◽  
Time Base ◽  
Suprachiasmatic Nuclei ◽  
Dark Cycle ◽  
Cellular Mechanisms ◽  
Circadian Control ◽  
Daily Cycles ◽  
Central Clock ◽  
Retinal Afferents

The secretion of hormones is temporally precise and periodic, oscillating over hours, days, and months. The circadian timekeeper within the suprachiasmatic nuclei (SCN) is central to this coordination, modulating the frequency of pulsatile release, maintaining daily cycles of secretion, and defining the time base for longer-term rhythms. This central clock is driven by cell-autonomous, transcriptional/posttranslational feedback loops incorporating Period (Per) and other clock genes. SCN neurons exist, however, within neural circuits, and an unresolved question is how SCN clock cells interact. By monitoring the SCN molecular clockwork using fluorescence and bioluminescence videomicroscopy of organotypic slices from mPer1::GFP and mPer1::luciferase transgenic mice, we show that interneuronal neuropeptidergic signaling via the vasoactive intestinal peptide (VIP)/PACAP2 (VPAC2) receptor for VIP (an abundant SCN neuropeptide) is necessary to maintain both the amplitude and the synchrony of clock cells in the SCN. Acute induction of mPer1 by light is, however, independent of VIP/VPAC2 signaling, demonstrating dissociation between cellular mechanisms mediating circadian control of the clockwork and those mediating its retinally dependent entrainment to the light/dark cycle. The latter likely involves the Ca2+/cAMP response elements of mPer genes, triggered by a MAPK cascade activated by retinal afferents to the SCN. In the absence of VPAC2 signaling, however, this cascade is inappropriately responsive to light during circadian daytime. Hence VPAC2-mediated signaling sustains the SCN cellular clockwork and is necessary both for interneuronal synchronization and appropriate entrainment to the light/dark cycle. In its absence, behavioral and endocrine rhythms are severely compromised.

scholarly journals Orexinergic Neurotransmission in Temperature Responses to Methamphetamine and Stress: Mathematical Modeling as a Data Assimilation Approach

PLoS ONE ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. e0126719 ◽  
Author(s):  
Abolhassan Behrouzvaziri ◽  
Daniel Fu ◽  
Patrick Tan ◽  
Yeonjoo Yoo ◽  
Maria V. Zaretskaia ◽  
...  
Keyword(s):  
Mathematical Modeling ◽  
Data Assimilation ◽  
Temperature Responses

Ionic mechanisms of electrical activity in somatic muscle of the nematodeAscaris lumbricoides

1976 ◽  
Vol 111 (2) ◽  
pp. 93-113 ◽  
Author(s):  
David A. Weisblat ◽  
Lou Byerly ◽  
Richard L. Russell
Keyword(s):  
Electrical Activity ◽  
Somatic Muscle ◽  
Ionic Mechanisms

scholarly journals Role of DBP in the Circadian Oscillatory Mechanism

2000 ◽  
Vol 20 (13) ◽  
pp. 4773-4781 ◽  
Author(s):  
Shun Yamaguchi ◽  
Shigeru Mitsui ◽  
Lily Yan ◽  
Kazuhiro Yagita ◽  
Shigeru Miyake ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Leucine Zipper ◽  
The Other ◽  
Suprachiasmatic Nuclei ◽  
Transcription Factor Family ◽  
Transcript Levels ◽  
Oscillatory Mechanism ◽  
Central Clock ◽  
E Boxes

ABSTRACT Transcript levels of DBP, a member of the PAR leucine zipper transcription factor family, exhibit a robust rhythm in suprachiasmatic nuclei, the mammalian circadian center. Here we report that DBP is able to activate the promoter of a putative clock oscillating gene,mPer1, by directly binding to the mPer1promoter. The mPer1 promoter is cooperatively activated by DBP and CLOCK-BMAL1. On the other hand, dbp transcription is activated by CLOCK-BMAL1 through E-boxes and inhibited by the mPER and mCRY proteins, as is the case for mPer1. Thus, a clock-controlled dbp gene may play an important role in central clock oscillation.

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