Pallidostriatal Projections Promote ß Oscillations in a Dopamine-Depleted Biophysical Network Model.
J Neurosci
; 36(20): 5556-71, 2016 05 18.
Article
en En
| MEDLINE
| ID: mdl-27194335
ABSTRACT
UNLABELLED In the basal ganglia, focused rhythmicity is an important feature of network activity at certain stages of motor processing. In disease, however, the basal ganglia develop amplified rhythmicity. Here, we demonstrate how the cellular architecture and network dynamics of an inhibitory loop in the basal ganglia yield exaggerated synchrony and locking to ß oscillations, specifically in the dopamine-depleted state. A key component of this loop is the pallidostriatal pathway, a well-characterized anatomical projection whose function has long remained obscure. We present a synaptic characterization of this pathway in mice and incorporate these data into a computational model that we use to investigate its influence over striatal activity under simulated healthy and dopamine-depleted conditions. Our model predicts that the pallidostriatal pathway influences striatal output preferentially during periods of synchronized activity within GPe. We show that, under dopamine-depleted conditions, this effect becomes a key component of a positive feedback loop between the GPe and striatum that promotes synchronization and rhythmicity. Our results generate novel predictions about the role of the pallidostriatal pathway in shaping basal ganglia activity in health and disease. SIGNIFICANCE STATEMENT This work demonstrates that functional connections from the globus pallidus externa (GPe) to striatum are substantially stronger onto fast-spiking interneurons (FSIs) than onto medium spiny neurons. Our circuit model suggests that when GPe spikes are synchronous, this pallidostriatal pathway causes synchronous FSI activity pauses, which allow a transient window of disinhibition for medium spiny neurons. In simulated dopamine-depletion, this GPe-FSI activity is necessary for the emergence of strong synchronization and the amplification and propagation of ß oscillations, which are a hallmark of parkinsonian circuit dysfunction. These results suggest that GPe may play a central role in propagating abnormal circuit activity to striatum, which in turn projects to downstream basal ganglia structures. These findings warrant further exploration of GPe as a target for interventions for Parkinson's disease.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ritmo beta
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Dopamina
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Globo Pálido
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Modelos Neurológicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Neurosci
Año:
2016
Tipo del documento:
Article
Pais de publicación:
EEUU
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ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA