Computational and theoretical insights into the homeostatic response to the decreased cell size of midbrain dopamine neurons.
Physiol Rep
; 9(2): e14709, 2021 01.
Article
em En
| MEDLINE
| ID: mdl-33484235
Midbrain dopamine neurons communicate signals of reward anticipation and attribution of salience. This capacity is distorted in heroin or cocaine abuse or in conditions such as human mania. A shared characteristic among rodent models of these behavioral disorders is that dopamine neurons in these animals acquired a small size and manifest an augmented spontaneous and burst activity. The biophysical mechanism underlying this increased excitation is currently unknown, but is believed to primarily follow from a substantial drop in K+ conductance secondary to morphology reduction. This work uses a dopamine neuron mathematical model to show, surprisingly, that under size diminution a reduction in K+ conductance is an adaptation that attempts to decrease cell excitability. The homeostatic response that preserves the intrinsic activity is the conservation of the ion channel density for each conductance; a result that is analytically demonstrated and challenges the experimentalist tendency to reduce intrinsic excitation to K+ conductance expression level. Another unexpected mechanism that buffers the raise in intrinsic activity is the presence of the ether-a-go-go-related gen K+ channel since its activation is illustrated to increase with size reduction. Computational experiments finally demonstrate that size attenuation results in the paradoxical enhancement of afferent-driven bursting as a reduced temporal summation indexed correlates with improved depolarization. This work illustrates, on the whole, that experimentation in the absence of mathematical models may lead to the erroneous interpretation of the counterintuitive aspects of empirical data.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Mesencéfalo
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Neurônios Dopaminérgicos
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Modelos Neurológicos
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Morfina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Physiol Rep
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Porto Rico
País de publicação:
Estados Unidos