Differentiating embryonic stem–derived neural stem cells show a maturation-dependent pattern of voltage-gated sodium current expression and graded action potentials

Biella, Gerardo; Febo, F. Di; Goffredo, Donato; Moiana, Alessia; Taglietti, Vanni; Conti, Luciano; Cattaneo, Elena; Toselli, Mauro

doi:10.1016/j.neuroscience.2007.07.021

Cited by 38 publications

(27 citation statements)

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“…The kinetics of these channels did not seem to matter [36]. Also, we [42] and others [43,44] have found that the inward currents induced with the same protocol used in the present study are virtually all composed of Na + currents. The fact that the changes of these characteristics correlated with the development of arousal-related behaviors during P3-P6 therefore indicates that the development of NGC neurons’ Na + channels plays an important role in the progress of arousal during this critical arousal development “time window”.…”

Section: Discussionsupporting

confidence: 58%

Development of Electrophysiological Properties of Nucleus Gigantocellularis Neurons Correlated with Increased CNS Arousal

Liu¹,

Pfaff²,

Calderon³

et al. 2016

Dev Neurosci

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Many types of data have suggested that neurons in the nucleus gigantocellularis (NGC) in the medullary reticular formation are critically important for CNS arousal and behavioral responsiveness. To extend this topic to a developmental framework, whole-cell patch-recorded characteristics of NGC neurons in brainstem slices and measures of arousal-dependent locomotion of postnatal day 3 (P3) to P6 mouse pups were measured and compared. These neuronal characteristics developed in an orderly, statistically significant monotonic manner over the course of P3-P6: (1) proportion of neurons capable of firing action potential (AP) trains, (2) AP amplitude, (3) AP threshold, (4) amplitude of inward and outward currents, (5) amplitude of negative peak currents, and (6) steady state currents (in I-V plot). These measurements reflect the maturation of sodium and certain potassium channels. Similarly, all measures of locomotion, latency to first movement, total locomotion duration, net locomotion distance, and total quiescence time also developed monotonically over P3-P6. Most importantly, electrophysiological and behavioral measures were significantly correlated. Interestingly, the behavioral measures were not correlated with frequency of excitatory postsynaptic currents or the proportion of neurons showing these currents, responses to a battery of neurotransmitter agents, or rapid activating potassium currents (including I_A). Considering the results here in the context of a large body of literature on NGC, we hypothesize that the developmental increase in NGC neuronal excitability participates in causing the increased behavioral responsivity during the postnatal period from P3 to P6.

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Section: Discussionsupporting

confidence: 58%

Development of Electrophysiological Properties of Nucleus Gigantocellularis Neurons Correlated with Increased CNS Arousal

Liu¹,

Pfaff²,

Calderon³

et al. 2016

Dev Neurosci

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“…This indicates that the development of the intrinsic neuronal physiology is surprisingly faithfully reproduced by mES cell-derived neurons. In comparison to neurons derived from neural stem cells (NS) expanded after differentiation from mES (Biella et al, 2007) our cells, which do not undergo further expansion, develop more rapidly. They produce repetitive fast APs at DIV 6, while the NS derived neurons reach that milestone not before DIV 10 or possibly later.…”

Section: Discussionmentioning

confidence: 73%

Functional differentiation of stem cell-derived neurons from different murine backgrounds

Barth¹,

Sütterlin²,

Nenniger³

et al. 2014

Front. Cell. Neurosci.

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Murine stem cell-derived neurons have been used to study a wide variety of neuropsychiatric diseases with a hereditary component, ranging from autism to Alzheimer’s. While a significant amount of data on their molecular biology has been generated, there is little data on the physiology of these cultures. Different mouse strains show clear differences in behavioral and other neurobiologically relevant readouts. We have studied the physiology of early differentiation and network formation in neuronal cultures derived from three different mouse embryonic stem cell lines. We have found largely overlapping patterns with some significant differences in the timing of the functional milestones. Neurons from R1 showed the fastest development of intrinsic excitability, while E14Tg2a and J1 were slower. This was also reflected in an earlier appearance of synaptic activity in R1 cultures, while E14Tg2a and J1 were delayed by up to 2 days. In conclusion, stem cells from all backgrounds could be successfully differentiated into functioning neural networks with similar developmental patterns. Differences in the timing of specific milestones, suggest that control cell lines and time-points should be carefully chosen when investigating genetic alterations that lead to subtle deficits in neuronal function.

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“…Sodium channels undergo a process of functional maturation increasing their ability to generate action potentials over time. 16,17 Mouse models have shown that the Na v 1.1 expression is low in neonates but increases in the second and third postnatal week. 18 Other ␣ subunits such as Na v 1.2 and Na v 1.3 may compensate for reduced Na v 1.1 function during this early stage of development.…”

Section: Resultsmentioning

confidence: 99%

Genotype–phenotype associations in SCN1A -related epilepsies

Zuberi

Brunklaus²,

Birch³

et al. 2011

Neurology

236

255

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Differentiating embryonic stem–derived neural stem cells show a maturation-dependent pattern of voltage-gated sodium current expression and graded action potentials

Cited by 38 publications

References 50 publications

Development of Electrophysiological Properties of Nucleus Gigantocellularis Neurons Correlated with Increased CNS Arousal

Development of Electrophysiological Properties of Nucleus Gigantocellularis Neurons Correlated with Increased CNS Arousal

Functional differentiation of stem cell-derived neurons from different murine backgrounds

Genotype–phenotype associations in SCN1A -related epilepsies

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