Cortical stimulation evokes abnormal responses in the dopamine-depleted rat basal ganglia

Hitoshi Kita, Takako Kita

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

The motor cortex (MC) sends massive projections to the basal ganglia. Motor disabilities in patients and animal models of Parkinson's disease (PD) may be caused by dopamine (DA)-depleted basal ganglia that abnormally process the information originating from MC. To study how DA depletion alters signal transfer in the basal ganglia, MC stimulation-induced (MC-induced) unitary responses were recorded from the basal ganglia of control and 6-hydroxydopamine-treated hemi-parkinsonian rats anesthetized with isoflurane. This report describes new findings about how DA depletion alters MC-induced responses. MC stimulation evokes an excitation in normally quiescent striatal (Str) neurons projecting to the globus pallidus external segment (GPe). After DA-depletion, the spontaneous firing of Str-GPe neurons increases, and MC stimulation evokes a shorter latency excitation followed by a long-lasting inhibition that was invisible under normal conditions. The increased firing activity and the newly exposed long inhibition generate tonic inhibition and a disfacilitation in GPe. The disfacilitation in GPe is then amplified in basal ganglia circuitry and generates a powerful long inhibition in the basal ganglia output nucleus, the globus pallidus internal segment. Intra-Str injections of a behaviorally effective dose of DA precursor L-3,4-dihydroxyphenylalanine effectively reversed these changes. These newly observed mechanisms also support the generation of pauses and burst activity commonly observed in the basal ganglia of parkinsonian subjects. These results suggest that the generation of abnormal response sequences in the basal ganglia contributes to the development of motor disabilities in PD and that intra-Str DA supplements effectively suppress abnormal signal transfer.

Original languageEnglish (US)
Pages (from-to)10311-10322
Number of pages12
JournalJournal of Neuroscience
Volume31
Issue number28
DOIs
StatePublished - Jul 13 2011

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Basal Ganglia
Dopamine
Motor Cortex
Globus Pallidus
Corpus Striatum
Parkinson Disease
Neurons
Oxidopamine
Isoflurane
Levodopa
Animal Models
Injections

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Cortical stimulation evokes abnormal responses in the dopamine-depleted rat basal ganglia. / Kita, Hitoshi; Kita, Takako.

In: Journal of Neuroscience, Vol. 31, No. 28, 13.07.2011, p. 10311-10322.

Research output: Contribution to journalArticle

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