Delta-frequency stimulation of cerebellar projections can compensate for schizophrenia-related medial frontal dysfunction.
Mol Psychiatry
; 22(5): 647-655, 2017 05.
Article
en En
| MEDLINE
| ID: mdl-28348382
ABSTRACT
Schizophrenia involves abnormalities in the medial frontal cortex that lead to cognitive deficits. Here we investigate a novel strategy to normalize medial frontal brain activity by stimulating cerebellar projections. We used an interval timing task to study elementary cognitive processing that requires both frontal and cerebellar networks that are disrupted in patients with schizophrenia. We report three novel findings. First, patients with schizophrenia had dysfunctional delta rhythms between 1-4 Hz in the medial frontal cortex. We explored cerebellar-frontal interactions in animal models and found that both frontal and cerebellar neurons were modulated during interval timing and had delta-frequency interactions. Finally, delta-frequency optogenetic stimulation of thalamic synaptic terminals of lateral cerebellar projection neurons rescued timing performance as well as medial frontal activity in a rodent model of schizophrenia-related frontal dysfunction. These data provide insight into how the cerebellum influences medial frontal networks and the role of the cerebellum in cognitive processing.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Esquizofrenia
/
Cerebelo
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Lóbulo Frontal
Tipo de estudio:
Observational_studies
/
Prognostic_studies
Límite:
Adult
/
Aged
/
Animals
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Mol Psychiatry
Asunto de la revista:
BIOLOGIA MOLECULAR
/
PSIQUIATRIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos