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Characterization of the axon initial segment (AIS) of motor neurons and identification of a para-AIS and a juxtapara-AIS, organized by protein 4.1B.

Duflocq A, Chareyre F, Giovannini M, Couraud F, Davenne M - BMC Biol. (2011)

Bottom Line: We also identified in all α motor neurons a hemi-node-type organization, with a contactin-associated protein (Caspr)+ paranode-type, as well as a Caspr2+ and Kv1+ juxtaparanode-type compartment, referred to as a para-AIS and a juxtapara (JXP)-AIS, adjacent to the AIS, where the myelin sheath begins.We found that Kv1 channels appear in the AIS, para-AIS and JXP-AIS concomitantly with myelination and are progressively excluded from the para-AIS.Protein 4.1B plays a key role in ensuring the proper molecular compartmentalization of this hemi-node-type region.

View Article: PubMed Central - HTML - PubMed

Affiliation: INSERM UMRS 952, 9 Quai St Bernard, F-75005, Paris, France.

ABSTRACT

Background: The axon initial segment (AIS) plays a crucial role: it is the site where neurons initiate their electrical outputs. Its composition in terms of voltage-gated sodium (Nav) and voltage-gated potassium (Kv) channels, as well as its length and localization determine the neuron's spiking properties. Some neurons are able to modulate their AIS length or distance from the soma in order to adapt their excitability properties to their activity level. It is therefore crucial to characterize all these parameters and determine where the myelin sheath begins in order to assess a neuron's excitability properties and ability to display such plasticity mechanisms. If the myelin sheath starts immediately after the AIS, another question then arises as to how would the axon be organized at its first myelin attachment site; since AISs are different from nodes of Ranvier, would this particular axonal region resemble a hemi-node of Ranvier?

Results: We have characterized the AIS of mouse somatic motor neurons. In addition to constant determinants of excitability properties, we found heterogeneities, in terms of AIS localization and Nav composition. We also identified in all α motor neurons a hemi-node-type organization, with a contactin-associated protein (Caspr)+ paranode-type, as well as a Caspr2+ and Kv1+ juxtaparanode-type compartment, referred to as a para-AIS and a juxtapara (JXP)-AIS, adjacent to the AIS, where the myelin sheath begins. We found that Kv1 channels appear in the AIS, para-AIS and JXP-AIS concomitantly with myelination and are progressively excluded from the para-AIS. Their expression in the AIS and JXP-AIS is independent from transient axonal glycoprotein-1 (TAG-1)/Caspr2, in contrast to juxtaparanodes, and independent from PSD-93. Data from mice lacking the cytoskeletal linker protein 4.1B show that this protein is necessary to form the Caspr+ para-AIS barrier, ensuring the compartmentalization of Kv1 channels and the segregation of the AIS, para-AIS and JXP-AIS.

Conclusions: α Motor neurons have heterogeneous AISs, which underlie different spiking properties. However, they all have a para-AIS and a JXP-AIS contiguous to their AIS, where the myelin sheath begins, which might limit some AIS plasticity. Protein 4.1B plays a key role in ensuring the proper molecular compartmentalization of this hemi-node-type region.

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Schematic drawing of a neuron showing the position of the axon initial segment (AIS). The AIS plays two crucial roles in neurons: it forms a barrier between the somatodendritic and axonal compartments maintaining the neuron's polarity, and the AIS is the site where electrical outputs are initiated: aggregation of specific voltage-gated ion channels allows spikes to be generated in response to inputs coming from the somatodendritic compartment. Once initiated, spikes are both propagated along the axon and retropropagated towards the soma and dendrites. When axons are myelinated, spikes are propagated in a saltatory fashion, from a node of Ranvier to the next one. What is the precise AIS ion channel composition? And does the myelin sheath start immediately after the AIS or, as a corollary, is the axon organized at the first myelin-anchoring site as a hemi-node of Ranvier, with a paranode-like and a juxtaparanode-like compartment? These questions are addressed in this study.
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Figure 1: Schematic drawing of a neuron showing the position of the axon initial segment (AIS). The AIS plays two crucial roles in neurons: it forms a barrier between the somatodendritic and axonal compartments maintaining the neuron's polarity, and the AIS is the site where electrical outputs are initiated: aggregation of specific voltage-gated ion channels allows spikes to be generated in response to inputs coming from the somatodendritic compartment. Once initiated, spikes are both propagated along the axon and retropropagated towards the soma and dendrites. When axons are myelinated, spikes are propagated in a saltatory fashion, from a node of Ranvier to the next one. What is the precise AIS ion channel composition? And does the myelin sheath start immediately after the AIS or, as a corollary, is the axon organized at the first myelin-anchoring site as a hemi-node of Ranvier, with a paranode-like and a juxtaparanode-like compartment? These questions are addressed in this study.

Mentions: The ability of the nervous system to convey information relies on the ability of its neurons to translate the information they receive into electrical outputs that can be propagated to their target cells. This crucial property takes place in the AIS (Figure 1), and is due to the aggregation of voltage-gated sodium (Nav) and voltage-gated potassium (Kv) channels. Depending on the combination and distribution of Nav and Kv channel isoforms at the AIS, neurons are able to generate spikes with different shapes, frequencies and patterns [1]. Very recently, AIS length and distance from the soma have also been shown to modify a neuron's spiking properties and to be modulated by neural activity [2-4]. It is therefore crucial to characterize all these parameters and determine where the myelin sheath begins in order to assess a given neuron's excitability properties and its ability to display the latter AIS plasticity mechanisms. Yet, only some of these criteria have been addressed, independently and in different neuronal types. In addition, despite the crucial role of the AIS as the spike-generating region, the molecular and potential domain organization of the axon immediately following the AIS, which might have an important impact on the neuron's spiking properties, has never been studied. If the myelin sheath starts immediately after the AIS, thus abutting an AIS instead of a node of Ranvier, another question arises: how would the axon be organized in this region? Since AISs differ from nodes of Ranvier in terms of molecular composition (hence of molecular clustering mechanisms) and development (AISs are preorganized when myelination takes place), would this first myelin-anchoring region resemble a hemi-node of Ranvier: would the AIS be, like nodes of Ranvier, flanked by a paranode-like and a juxtaparanode-like compartment (Figure 1)?


Characterization of the axon initial segment (AIS) of motor neurons and identification of a para-AIS and a juxtapara-AIS, organized by protein 4.1B.

Duflocq A, Chareyre F, Giovannini M, Couraud F, Davenne M - BMC Biol. (2011)

Schematic drawing of a neuron showing the position of the axon initial segment (AIS). The AIS plays two crucial roles in neurons: it forms a barrier between the somatodendritic and axonal compartments maintaining the neuron's polarity, and the AIS is the site where electrical outputs are initiated: aggregation of specific voltage-gated ion channels allows spikes to be generated in response to inputs coming from the somatodendritic compartment. Once initiated, spikes are both propagated along the axon and retropropagated towards the soma and dendrites. When axons are myelinated, spikes are propagated in a saltatory fashion, from a node of Ranvier to the next one. What is the precise AIS ion channel composition? And does the myelin sheath start immediately after the AIS or, as a corollary, is the axon organized at the first myelin-anchoring site as a hemi-node of Ranvier, with a paranode-like and a juxtaparanode-like compartment? These questions are addressed in this study.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198992&req=5

Figure 1: Schematic drawing of a neuron showing the position of the axon initial segment (AIS). The AIS plays two crucial roles in neurons: it forms a barrier between the somatodendritic and axonal compartments maintaining the neuron's polarity, and the AIS is the site where electrical outputs are initiated: aggregation of specific voltage-gated ion channels allows spikes to be generated in response to inputs coming from the somatodendritic compartment. Once initiated, spikes are both propagated along the axon and retropropagated towards the soma and dendrites. When axons are myelinated, spikes are propagated in a saltatory fashion, from a node of Ranvier to the next one. What is the precise AIS ion channel composition? And does the myelin sheath start immediately after the AIS or, as a corollary, is the axon organized at the first myelin-anchoring site as a hemi-node of Ranvier, with a paranode-like and a juxtaparanode-like compartment? These questions are addressed in this study.
Mentions: The ability of the nervous system to convey information relies on the ability of its neurons to translate the information they receive into electrical outputs that can be propagated to their target cells. This crucial property takes place in the AIS (Figure 1), and is due to the aggregation of voltage-gated sodium (Nav) and voltage-gated potassium (Kv) channels. Depending on the combination and distribution of Nav and Kv channel isoforms at the AIS, neurons are able to generate spikes with different shapes, frequencies and patterns [1]. Very recently, AIS length and distance from the soma have also been shown to modify a neuron's spiking properties and to be modulated by neural activity [2-4]. It is therefore crucial to characterize all these parameters and determine where the myelin sheath begins in order to assess a given neuron's excitability properties and its ability to display the latter AIS plasticity mechanisms. Yet, only some of these criteria have been addressed, independently and in different neuronal types. In addition, despite the crucial role of the AIS as the spike-generating region, the molecular and potential domain organization of the axon immediately following the AIS, which might have an important impact on the neuron's spiking properties, has never been studied. If the myelin sheath starts immediately after the AIS, thus abutting an AIS instead of a node of Ranvier, another question arises: how would the axon be organized in this region? Since AISs differ from nodes of Ranvier in terms of molecular composition (hence of molecular clustering mechanisms) and development (AISs are preorganized when myelination takes place), would this first myelin-anchoring region resemble a hemi-node of Ranvier: would the AIS be, like nodes of Ranvier, flanked by a paranode-like and a juxtaparanode-like compartment (Figure 1)?

Bottom Line: We also identified in all α motor neurons a hemi-node-type organization, with a contactin-associated protein (Caspr)+ paranode-type, as well as a Caspr2+ and Kv1+ juxtaparanode-type compartment, referred to as a para-AIS and a juxtapara (JXP)-AIS, adjacent to the AIS, where the myelin sheath begins.We found that Kv1 channels appear in the AIS, para-AIS and JXP-AIS concomitantly with myelination and are progressively excluded from the para-AIS.Protein 4.1B plays a key role in ensuring the proper molecular compartmentalization of this hemi-node-type region.

View Article: PubMed Central - HTML - PubMed

Affiliation: INSERM UMRS 952, 9 Quai St Bernard, F-75005, Paris, France.

ABSTRACT

Background: The axon initial segment (AIS) plays a crucial role: it is the site where neurons initiate their electrical outputs. Its composition in terms of voltage-gated sodium (Nav) and voltage-gated potassium (Kv) channels, as well as its length and localization determine the neuron's spiking properties. Some neurons are able to modulate their AIS length or distance from the soma in order to adapt their excitability properties to their activity level. It is therefore crucial to characterize all these parameters and determine where the myelin sheath begins in order to assess a neuron's excitability properties and ability to display such plasticity mechanisms. If the myelin sheath starts immediately after the AIS, another question then arises as to how would the axon be organized at its first myelin attachment site; since AISs are different from nodes of Ranvier, would this particular axonal region resemble a hemi-node of Ranvier?

Results: We have characterized the AIS of mouse somatic motor neurons. In addition to constant determinants of excitability properties, we found heterogeneities, in terms of AIS localization and Nav composition. We also identified in all α motor neurons a hemi-node-type organization, with a contactin-associated protein (Caspr)+ paranode-type, as well as a Caspr2+ and Kv1+ juxtaparanode-type compartment, referred to as a para-AIS and a juxtapara (JXP)-AIS, adjacent to the AIS, where the myelin sheath begins. We found that Kv1 channels appear in the AIS, para-AIS and JXP-AIS concomitantly with myelination and are progressively excluded from the para-AIS. Their expression in the AIS and JXP-AIS is independent from transient axonal glycoprotein-1 (TAG-1)/Caspr2, in contrast to juxtaparanodes, and independent from PSD-93. Data from mice lacking the cytoskeletal linker protein 4.1B show that this protein is necessary to form the Caspr+ para-AIS barrier, ensuring the compartmentalization of Kv1 channels and the segregation of the AIS, para-AIS and JXP-AIS.

Conclusions: α Motor neurons have heterogeneous AISs, which underlie different spiking properties. However, they all have a para-AIS and a JXP-AIS contiguous to their AIS, where the myelin sheath begins, which might limit some AIS plasticity. Protein 4.1B plays a key role in ensuring the proper molecular compartmentalization of this hemi-node-type region.

Show MeSH
Related in: MedlinePlus