Journal article
Sodium and calcium mechanisms of rhythmic bursting in excitatory neural networks of the pre-Bötzinger complex: a computational modelling study
The European journal of neuroscience, v 37(2), pp 212-230
Jan 2013
PMID: 23121313
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The neural mechanisms generating rhythmic bursting activity in the mammalian brainstem, particularly in the pre-Bötzinger complex (pre-BötC), which is involved in respiratory rhythm generation, and in the spinal cord (e.g. locomotor rhythmic activity) that persist after blockade of synaptic inhibition remain poorly understood. Experimental studies in rodent medullary slices containing the pre-BötC identified two mechanisms that could potentially contribute to the generation of rhythmic bursting: one based on the persistent Na
+
current (
I
NaP
), and the other involving the voltage-gated Ca
2+
current (
I
Ca
) and the Ca
2+
-activated nonspecific cation current (
I
CAN
), activated by intracellular Ca
2+
accumulated from extracellular and intracellular sources. However, the involvement and relative roles of these mechanisms in rhythmic bursting are still under debate. In this theoretical/modelling study, we investigated Na
+
-dependent and Ca
2+
-dependent bursting generated in single cells and heterogeneous populations of synaptically interconnected excitatory neurons with
I
NaP
and
I
Ca
randomly distributed within populations. We analysed the possible roles of network connections, ionotropic and metabotropic synaptic mechanisms, intracellular Ca
2+
release, and the Na
+
/K
+
pump in rhythmic bursting generated under different conditions. We show that a heterogeneous population of excitatory neurons can operate in different oscillatory regimes with bursting dependent on
I
NaP
and/or
I
CAN
, or independent of both. We demonstrate that the operating bursting mechanism may depend on neuronal excitation, synaptic interactions within the network, and the relative expression of particular ionic currents. The existence of multiple oscillatory regimes and their state dependence demonstrated in our models may explain different rhythmic activities observed in the pre-BötC and other brainstem/spinal cord circuits under different experimental conditions.
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Details
- Title
- Sodium and calcium mechanisms of rhythmic bursting in excitatory neural networks of the pre-Bötzinger complex: a computational modelling study
- Creators
- Patrick E Jasinski - Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USAYaroslav I Molkov - Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USANatalia A Shevtsova - Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USAJeffrey C Smith - Cellular and Systems Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USAIlya A Rybak - Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA
- Publication Details
- The European journal of neuroscience, v 37(2), pp 212-230
- Publisher
- Wiley
- Grant note
- R01 NS081713 || NS / National Institute of Neurological Disorders and Stroke : NINDS R01 NS057815 || NS / National Institute of Neurological Disorders and Stroke : NINDS R01 NS069220 || NS / National Institute of Neurological Disorders and Stroke : NINDS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000313835700005
- Scopus ID
- 2-s2.0-84872670622
- Other Identifier
- 991014877811904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences