scholarly journals Mis-expression of the BK K+ channel disrupts suprachiasmatic nucleus circuit rhythmicity and alters clock-controlled behavior

2013 ◽  
Vol 304 (4) ◽  
pp. C299-C311 ◽  
Author(s):  
Jenna R. Montgomery ◽  
Joshua P. Whitt ◽  
Breanne N. Wright ◽  
Michael H. Lai ◽  
Andrea L. Meredith
Keyword(s):  
Suprachiasmatic Nucleus ◽  
Neural Circuit ◽  
High Amplitude ◽  
Circadian Rhythmicity ◽  
K Channel ◽  
Current Channel ◽  
Behavioral Rhythm ◽  
Ionic Mechanisms ◽  
Almost All ◽  
Circadian Behavior

In mammals, almost all aspects of circadian rhythmicity are attributed to activity in a discrete neural circuit of the hypothalamus, the suprachiasmatic nucleus (SCN). A 24-h rhythm in spontaneous firing is the fundamental neural intermediary to circadian behavior, but the ionic mechanisms that pattern circuit rhythmicity, and the integrated impact on behavior, are not well studied. Here, we demonstrate that daily modulation of a major component of the nighttime-phased suppressive K+ current, encoded by the BK Ca2+-activated K+ current channel (KCa1.1 or Kcnma1), is a critical arbiter of circadian rhythmicity in the SCN circuit. Aberrant induction of BK current during the day in transgenic mice using a Per1 promoter ( Tg-BK R207Q) reduced SCN firing or silenced neurons, decreasing the circadian amplitude of the ensemble circuit rhythm. Changes in cellular and circuit excitability in Tg-BK R207Q SCNs were correlated with elongated behavioral active periods and enhanced responses to phase-shifting stimuli. Unexpectedly, despite the severe reduction in circuit amplitude, circadian behavioral amplitudes in Tg-BK R207Q mice were relatively normal. These data demonstrate that downregulation of the BK current during the day is essential for the high amplitude neural activity pattern in the SCN that restricts locomotor activity to the appropriate phase and maintains the clock's robustness against perturbation. However, a residually rhythmic subset prevails over the ensemble circuit to drive the fundamental circadian behavioral rhythm.

scholarly journals Drugs of Abuse Can Entrain Circadian Rhythms

2007 ◽  
Vol 7 ◽  
pp. 203-212 ◽  
Author(s):  
Ann E. K. Kosobud ◽  
Andrea G. Gillman ◽  
Joseph K. Leffel ◽  
Norman C. Pecoraro ◽  
G. V. Rebec ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Circadian Rhythms ◽  
Drug Metabolism ◽  
Suprachiasmatic Nucleus ◽  
Drugs Of Abuse ◽  
Social Cues ◽  
Dark Cycle ◽  
Drug Reward ◽  
Locomotor Stimulation ◽  
Almost All

Circadian rhythms prepare organisms for predictable events during the Earth's 24-h day. These rhythms are entrained by a variety of stimuli. Light is the most ubiquitous and best known zeitgeber, but a number of others have been identified, including food, social cues, locomotor activity, and, most recently drugs of abuse. Given the diversity of zeitgebers, it is probably not surprising that genes capable of clock functions are located throughout almost all organs and tissues. Recent evidence suggests that drugs of abuse can directly entrain some circadian rhythms. We have report here that entrainment by drugs of abuse is independent of the suprachiasmatic nucleus and the light/dark cycle, is not dependent on direct locomotor stimulation, and is shared by a variety of classes of drugs of abuse. We suggest that drug-entrained rhythms reflect variations in underlying neurophysiological states. This could be the basis for known daily variations in drug metabolism, tolerance, and sensitivity to drug reward. These rhythms could also take the form of daily periods of increased motivation to seek and take drugs, and thus contribute to abuse, addiction and relapse.

scholarly journals Temporally chimeric mice reveal flexibility of circadian period-setting in the suprachiasmatic nucleus

2016 ◽  
Vol 113 (13) ◽  
pp. 3657-3662 ◽  
Author(s):  
Nicola J. Smyllie ◽  
Johanna E. Chesham ◽  
Ryan Hamnett ◽  
Elizabeth S. Maywood ◽  
Michael H. Hastings
Keyword(s):  
Gene Expression ◽  
Suprachiasmatic Nucleus ◽  
Feedback Loops ◽  
Chimeric Mice ◽  
Pacemaker Cells ◽  
Daily Behavior ◽  
New Perspective ◽  
Circadian Behavior

The suprachiasmatic nucleus (SCN) is the master circadian clock controlling daily behavior in mammals. It consists of a heterogeneous network of neurons, in which cell-autonomous molecular feedback loops determine the period and amplitude of circadian oscillations of individual cells. In contrast, circuit-level properties of coherence, synchrony, and ensemble period are determined by intercellular signals and are embodied in a circadian wave of gene expression that progresses daily across the SCN. How cell-autonomous and circuit-level mechanisms interact in timekeeping is poorly understood. To explore this interaction, we used intersectional genetics to create temporally chimeric mice with SCN containing dopamine 1a receptor (Drd1a) cells with an intrinsic period of 24 h alongside non-Drd1a cells with 20-h clocks. Recording of circadian behavior in vivo alongside cellular molecular pacemaking in SCN slices in vitro demonstrated that such chimeric circuits form robust and resilient circadian clocks. It also showed that the computation of ensemble period is nonlinear. Moreover, the chimeric circuit sustained a wave of gene expression comparable to that of nonchimeric SCN, demonstrating that this circuit-level property is independent of differences in cell-intrinsic periods. The relative dominance of 24-h Drd1a and 20-h non-Drd1a neurons in setting ensemble period could be switched by exposure to resonant or nonresonant 24-h or 20-h lighting cycles. The chimeric circuit therefore reveals unanticipated principles of circuit-level operation underlying the emergent plasticity, resilience, and robustness of the SCN clock. The spontaneous and light-driven flexibility of period observed in chimeric mice provides a new perspective on the concept of SCN pacemaker cells.

scholarly journals Overloads resulting from the volume of movements in choreography and sports. Message IV. Pelvis and hip joints apophysitis (diachronic analysis)

2020 ◽  
Vol 64 (4) ◽  
pp. 169-199
Author(s):  
O.S. Vasiliev ◽  
◽  
I.A. Stepanik ◽  
S.P. Levushkin ◽  
A.V. Rokhlin ◽  
...  
Keyword(s):  
Sports Injuries ◽  
High Amplitude ◽  
Overuse Injuries ◽  
Hip Joints ◽  
Optimal Method ◽  
Acute Injuries ◽  
Modern Methods ◽  
Diachronic Analysis ◽  
The Aesthetic ◽  
Almost All

High-amplitude movements in ballet and sports significantly increase the load on the tendon-muscleligament apparatus of the pelvis and hip joints, which leads to apophysites. The aesthetic demands for movements requiring leg turnout significantly modifies the biomechanics of musculoskeletal motion, creating overuse in structures that are rarely "overused" during natural (without turning legs out) movements. Overuse injuries in these children and adolescents are much more common than acute injuries. Most apophysitis, especially apophysitis of pelvic bones and hip joints, remain undiagnosed and mixed up with usual sports injuries. The difficulty in diagnosing the apophysites is that almost all modern methods of instrumental diagnostics are not apophysitis specific and, in most cases, visualize a variety of age norm. Physical examination still remains the optimal method of apophysites diagnostics

scholarly journals Contribution of KCNQ and TREK Channels to the Resting Membrane Potential in Sympathetic Neurons at Physiological Temperature

2020 ◽  
Vol 21 (16) ◽  
pp. 5796
Author(s):  
Paula Rivas-Ramírez ◽  
Antonio Reboreda ◽  
Lola Rueda-Ruzafa ◽  
Salvador Herrera-Pérez ◽  
Jose Antonio Lamas
Keyword(s):  
Membrane Potential ◽  
Room Temperature ◽  
Sympathetic Neurons ◽  
K Channel ◽  
Resting Membrane Potential ◽  
Physiological Temperature ◽  
M Current ◽  
Key Players ◽  
Cervical Ganglion ◽  
Ionic Mechanisms

The ionic mechanisms controlling the resting membrane potential (RMP) in superior cervical ganglion (SCG) neurons have been widely studied and the M-current (IM, KCNQ) is one of the key players. Recently, with the discovery of the presence of functional TREK-2 (TWIK-related K+ channel 2) channels in SCG neurons, another potential main contributor for setting the value of the resting membrane potential has appeared. In the present work, we quantified the contribution of TREK-2 channels to the resting membrane potential at physiological temperature and studied its role in excitability using patch-clamp techniques. In the process we have discovered that TREK-2 channels are sensitive to the classic M-current blockers linopirdine and XE991 (IC50 = 0.310 ± 0.06 µM and 0.044 ± 0.013 µM, respectively). An increase from room temperature (23 °C) to physiological temperature (37 °C) enhanced both IM and TREK-2 currents. Likewise, inhibition of IM by tetraethylammonium (TEA) and TREK-2 current by XE991 depolarized the RMP at room and physiological temperatures. Temperature rise also enhanced adaptation in SCG neurons which was reduced due to TREK-2 and IM inhibition by XE991 application. In summary, TREK-2 and M currents contribute to the resting membrane potential and excitability at room and physiological temperature in the primary culture of mouse SCG neurons.

scholarly journals Minireview: The Neuroendocrinology of the Suprachiasmatic Nucleus as a Conductor of Body Time in Mammals

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 5640-5647 ◽  
Author(s):  
Ilia N. Karatsoreos ◽  
Rae Silver
Keyword(s):  
Circadian Rhythms ◽  
Suprachiasmatic Nucleus ◽  
Hormone Secretion ◽  
Gonadal Hormone ◽  
Multiple Levels ◽  
And Behavior ◽  
Circadian Behavior ◽  
The Brain ◽  
Indirect Route ◽  
Photic Input

Circadian rhythms in physiology and behavior are regulated by a master clock resident in the suprachiasmatic nucleus (SCN) of the hypothalamus, and dysfunctions in the circadian system can lead to serious health effects. This paper reviews the organization of the SCN as the brain clock, how it regulates gonadal hormone secretion, and how androgens modulate aspects of circadian behavior known to be regulated by the SCN. We show that androgen receptors are restricted to a core SCN region that receives photic input as well as afferents from arousal systems in the brain. We suggest that androgens modulate circadian behavior directly via actions on the SCN and that both androgens and estrogens modulate circadian rhythms through an indirect route, by affecting overall activity and arousal levels. Thus, this system has multiple levels of regulation; the SCN regulates circadian rhythms in gonadal hormone secretion, and hormones feed back to influence SCN functions.

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