Zn2+ enhances the intrinsic bursting activity of a rat thalamic relay neuron

My thesis studies had stimulated an interest in the mamillothalamic pathways but also some puzzlement because we knew nothing about the nature of the messages passing along these pathways. Several laboratories were studying the thalamic relay of sensory pathways with great success during my post-doctoral years. Each sensory relay could be understood in terms of the appropriate sensory input, but we had no way of knowing the meaning of the mamillothalamic messages. I introduce these nuclei as an example of the many thalamic nuclei about whose input functions we still know little or nothing. Early clinical studies of mamillary lesions had suggested a role in memory formation, whereas evidence from cortical lesions suggested a role in emotional experiences. Studies of the smallest of the three nuclei forming these pathways then showed it to be concerned with sensing head direction, relevant but not sufficient for defining an animal’s position in space. More recent studies based on studies of cortical activity or cortical damage have provided a plethora of suggestions: as so often, the answers reported depend on the questions asked. That simple conclusion is relevant for all transthalamic pathways. The evidence introduced in Chapter 1, that thalamocortical messages have dual meanings, suggests that we need to rethink our questions. It may prove useful to look at the motor outputs of relevant cortical areas to get clues about some appropriate questions.

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GnRH neurons and episodic bursting activity

Trends in Endocrinology and Metabolism ◽

10.1016/s1043-2760(02)00698-7 ◽

2002 ◽

Vol 13 (10) ◽

pp. 409-410 ◽

Cited By ~ 23

Author(s):

Martin J Kelly ◽

Edward J Wagner

Keyword(s):

Gnrh Neurons ◽

Bursting Activity

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Intracellular Na+ Modulates Pacemaking Activity in Murine Sinoatrial Node Myocytes: An In Silico Analysis

International Journal of Molecular Sciences ◽

10.3390/ijms22115645 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5645

Author(s):

Stefano Morotti ◽

Haibo Ni ◽

Colin H. Peters ◽

Christian Rickert ◽

Ameneh Asgari-Targhi ◽

...

Keyword(s):

Heart Failure ◽

Membrane Potential ◽

In Silico ◽

Sinoatrial Node ◽

In Silico Analysis ◽

Ankyrin B ◽

Deficient Mice ◽

Silico Analysis ◽

Bursting Activity

Background: The mechanisms underlying dysfunction in the sinoatrial node (SAN), the heart’s primary pacemaker, are incompletely understood. Electrical and Ca2+-handling remodeling have been implicated in SAN dysfunction associated with heart failure, aging, and diabetes. Cardiomyocyte [Na+]i is also elevated in these diseases, where it contributes to arrhythmogenesis. Here, we sought to investigate the largely unexplored role of Na+ homeostasis in SAN pacemaking and test whether [Na+]i dysregulation may contribute to SAN dysfunction. Methods: We developed a dataset-specific computational model of the murine SAN myocyte and simulated alterations in the major processes of Na+ entry (Na+/Ca2+ exchanger, NCX) and removal (Na+/K+ ATPase, NKA). Results: We found that changes in intracellular Na+ homeostatic processes dynamically regulate SAN electrophysiology. Mild reductions in NKA and NCX function increase myocyte firing rate, whereas a stronger reduction causes bursting activity and loss of automaticity. These pathologic phenotypes mimic those observed experimentally in NCX- and ankyrin-B-deficient mice due to altered feedback between the Ca2+ and membrane potential clocks underlying SAN firing. Conclusions: Our study generates new testable predictions and insight linking Na+ homeostasis to Ca2+ handling and membrane potential dynamics in SAN myocytes that may advance our understanding of SAN (dys)function.

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Sodium Currents in Neurons From the Rostroventrolateral Medulla of the Rat

Journal of Neurophysiology ◽

10.1152/jn.00150.2003 ◽

2003 ◽

Vol 90 (3) ◽

pp. 1635-1642 ◽

Cited By ~ 40

Author(s):

Ilya A. Rybak ◽

Krzysztof Ptak ◽

Natalia A. Shevtsova ◽

Donald R. McCrimmon

Keyword(s):

Sodium Channels ◽

Sodium Current ◽

Cell Voltage ◽

Kinetic Properties ◽

Persistent Sodium Current ◽

Sodium Currents ◽

Bötzinger Complex ◽

Window Current ◽

Bursting Activity

Rapidly inactivating and persistent sodium currents have been characterized in acutely dissociated neurons from the area of rostroventrolateral medulla that included the pre-Bötzinger Complex. As demonstrated in many studies in vitro, this area can generate endogenous rhythmic bursting activity. Experiments were performed on neonate and young rats (P1-15). Neurons were investigated using the whole cell voltage-clamp technique. Standard activation and inactivation protocols were used to characterize the steady-state and kinetic properties of the rapidly inactivating sodium current. Slow depolarizing ramp protocols were used to characterize the noninactivating sodium current. The “window” component of the rapidly inactivating sodium current was calculated using mathematical modeling. The persistent sodium current was revealed by subtraction of the window current from the total noninactivating sodium current. Our results provide evidence of the presence of persistent sodium currents in neurons of the rat rostroventrolateral medulla and determine voltage-gated characteristics of activation and inactivation of rapidly inactivating and persistent sodium channels in these neurons.

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