Characterization of the axon initial segment of mice substantia nigra dopaminergic neurons.
J Comp Neurol
; 525(16): 3529-3542, 2017 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-28734032
The axon initial segment (AIS) is the site of initiation of action potentials and influences action potential waveform, firing pattern, and rate. In view of the fundamental aspects of motor function and behavior that depend on the firing of substantia nigra pars compacta (SNc) dopaminergic neurons, we identified and characterized their AIS in the mouse. Immunostaining for tyrosine hydroxylase (TH), sodium channels (Nav ) and ankyrin-G (Ank-G) was used to visualize the AIS of dopaminergic neurons. Reconstructions of sampled AIS of dopaminergic neurons revealed variable lengths (12-60 µm) and diameters (0.2-0.8 µm), and an average of 50% reduction in diameter between their widest and thinnest parts. Ultrastructural analysis revealed submembranous localization of Ank-G at nodes of Ranvier and AIS. Serial ultrathin section analysis and 3D reconstructions revealed that Ank-G colocalized with TH only at the AIS. Few cases of synaptic innervation of the AIS of dopaminergic neurons were observed. mRNA in situ hybridization of brain-specific Nav subunits revealed the expression of Nav 1.2 by most SNc neurons and a small proportion expressing Nav 1.6. The presence of sodium channels, along with the submembranous location of Ank-G is consistent with the role of AIS in action potential generation. Differences in the size of the AIS likely underlie differences in firing pattern, while the tapering diameter of AIS may define a trigger zone for action potentials. Finally, the conspicuous expression of Nav 1.2 by the majority of dopaminergic neurons may explain their high threshold for firing and their low discharge rate.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Substância Negra
/
Neurônios Dopaminérgicos
/
Segmento Inicial do Axônio
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Comp Neurol
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Chile
País de publicação:
Estados Unidos