Action potential generation requires a high sodium channel density in the axon initial segment

2008 ◽  
Vol 11 (2) ◽  
pp. 178-186 ◽  
Author(s):  
Maarten H P Kole ◽  
Susanne U Ilschner ◽  
Björn M Kampa ◽  
Stephen R Williams ◽  
Peter C Ruben ◽  
...  
Keyword(s):  
Action Potential ◽  
Sodium Channel ◽  
Initial Segment ◽  
Axon Initial Segment ◽  
Action Potential Generation ◽  
Potential Generation ◽  
High Sodium ◽  
Channel Density

scholarly journals COUP-TFI regulates diameter of the axon initial segment in the mammalian neocortex

2020 ◽  
Author(s):  
Xuanyuan Wu ◽  
Haixiang Li ◽  
Jiechang Huang ◽  
Cheng Xiao ◽  
Shuijin He
Keyword(s):  
Action Potential ◽  
Initial Segment ◽  
Neuronal Excitability ◽  
Developmental Stages ◽  
Pyramidal Cells ◽  
Axon Initial Segment ◽  
Action Potential Generation ◽  
Potential Generation ◽  
Cell Ablation ◽  
Specialized Structure

AbstractThe axon initial segment is a specialized structure that controls neuronal excitability by generating action potentials. Currently, AIS plasticity with regard to changes in length and location in response to neural activity has been extensively investigated, but how AIS diameter is regulated remains elusive. Here we report that COUP-TFI is an essential regulator of AIS diameter in both developing and adult mouse neocortex. Embryonic ablation of COUP-TFI prevented expansion of AIS diameter that occurs during postnatal development in layer II/III pyramidal cells of the mouse motor cortex, thereby leading to an impairment of action potential generation. Inactivation of COUP-TFI in adult neurons also led to reduced AIS diameter and impaired action potential generation. In contrast to different developmental stages, single-cell ablation and global ablation produced opposite effects on spontaneous network in COUP-TFI-deficient neurons. Further, mice exhibited less anxiety-like behaviors after postnatal inactivation of COUP-TFI induced by tamoxifen. Our results demonstrate that COUP-TFI is indispensable for both expansion and maintenance of AIS diameter and that a change in AIS diameter fine-tunes synaptic inputs through a metaplasticity mechanism in the adult neocortex.

scholarly journals Activity-dependent mismatch between axo-axonic synapses and the axon initial segment controls neuronal output

2015 ◽  
Vol 112 (31) ◽  
pp. 9757-9762 ◽  
Author(s):  
Winnie Wefelmeyer ◽  
Daniel Cattaert ◽  
Juan Burrone
Keyword(s):  
Action Potential ◽  
Hippocampal Neurons ◽  
Initial Segment ◽  
Pyramidal Neurons ◽  
Neuronal Cell ◽  
Axon Initial Segment ◽  
Action Potential Generation ◽  
Potential Generation ◽  
Auditory Nucleus

The axon initial segment (AIS) is a structure at the start of the axon with a high density of sodium and potassium channels that defines the site of action potential generation. It has recently been shown that this structure is plastic and can change its position along the axon, as well as its length, in a homeostatic manner. Chronic activity-deprivation paradigms in a chick auditory nucleus lead to a lengthening of the AIS and an increase in neuronal excitability. On the other hand, a long-term increase in activity in dissociated rat hippocampal neurons results in an outward movement of the AIS and a decrease in the cell’s excitability. Here, we investigated whether the AIS is capable of undergoing structural plasticity in rat hippocampal organotypic slices, which retain the diversity of neuronal cell types present at postnatal ages, including chandelier cells. These interneurons exclusively target the AIS of pyramidal neurons and form rows of presynaptic boutons along them. Stimulating individual CA1 pyramidal neurons that express channelrhodopsin-2 for 48 h leads to an outward shift of the AIS. Intriguingly, both the pre- and postsynaptic components of the axo-axonic synapses did not change position after AIS relocation. We used computational modeling to explore the functional consequences of this partial mismatch and found that it allows the GABAergic synapses to strongly oppose action potential generation, and thus downregulate pyramidal cell excitability. We propose that this spatial arrangement is the optimal configuration for a homeostatic response to long-term stimulation.

scholarly journals Curbing action potential generation or ATP-synthase leads to a decrease in in-cell pyruvate dehydrogenase activity in rat cerebrum slices

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Benjamin Grieb ◽  
Sivaranjan Uppala ◽  
Gal Sapir ◽  
David Shaul ◽  
J. Moshe Gomori ◽  
...  
Keyword(s):  
Action Potential ◽  
Atp Synthase ◽  
Neural Activity ◽  
Pyruvate Dehydrogenase ◽  
Cerebral Metabolism ◽  
Neuronal Firing ◽  
Action Potential Generation ◽  
Potential Generation ◽  
Drastic Increase ◽  
Rat Cerebrum

AbstractDirect and real-time monitoring of cerebral metabolism exploiting the drastic increase in sensitivity of hyperpolarized 13C-labeled metabolites holds the potential to report on neural activity via in-cell metabolic indicators. Here, we followed the metabolic consequences of curbing action potential generation and ATP-synthase in rat cerebrum slices, induced by tetrodotoxin and oligomycin, respectively. The results suggest that pyruvate dehydrogenase (PDH) activity in the cerebrum is 4.4-fold higher when neuronal firing is unperturbed. The PDH activity was 7.4-fold reduced in the presence of oligomycin, and served as a pharmacological control for testing the ability to determine changes to PDH activity in viable cerebrum slices. These findings may open a path towards utilization of PDH activity, observed by magnetic resonance of hyperpolarized 13C-labeled pyruvate, as a reporter of neural activity.

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