Graded 6-OHDA-induced dopamine depletion in the nigrostriatal pathway evokes progressive pathological neuronal activities in the subthalamic nucleus of a hemi-parkinsonian mouse

Sunghee Estelle Park, Kang Il Song, Hyungmin Kim, Seok Chung, Inchan Youn

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Recent studies have established methods for establishing a rodent model that mimics progressive stages of human Parkinson's disease (PD), via injection of graded doses of 6-hydroxydopamine (6-OHDA) into regions within the nigrostriatal pathway. However, the electrophysiological characteristics of the subthalamic nucleus (STN) in this model have not been fully elucidated in this model. This study aimed to investigate changes in the neuronal activity of the STN in a graded mouse model of PD. Increasing doses of 6-OHDA were unilaterally injected into the medial forebrain bundle (MFB) to produce a hemi-parkinsonian mouse model, mimicking early, moderate, advanced, and severe stages of human PD. Mice treated with higher doses of 6-OHDA demonstrated significantly lower rates of use of the impaired (contralateral) forelimb during wall contact, relative to sham mice. The STN firing rate was significantly increased in groups with >75% dopaminergic cell loss in the substantia nigra pars compacta (SNc), whereas little increase was observed in groups with partial lesions of the SNc, relative to the sham group. In addition, firing patterns of the STN in groups treated with higher doses of 6-OHDA became more irregular and exhibited burst-like patterns of activity, with dominant slow wave oscillations in the frequency range of 0.3–2.5 Hz. Our results demonstrated a strong correlation between neuronal activities in the STN and dopamine depletion in the nigrostriatal pathway, which can be manipulated by variation of 6-OHDA doses.

Original languageEnglish
Pages (from-to)42-47
Number of pages6
JournalBehavioural Brain Research
Volume344
DOIs
Publication statusPublished - 2018 May 15

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Subthalamic Nucleus
Oxidopamine
Dopamine
Parkinson Disease
Medial Forebrain Bundle
Forelimb
Rodentia
Injections

Keywords

  • 6-Hydroxydopamine
  • Electrophysiology
  • Medial forebrain bundle
  • Parkinson's disease
  • Subthalamic nucleus

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Graded 6-OHDA-induced dopamine depletion in the nigrostriatal pathway evokes progressive pathological neuronal activities in the subthalamic nucleus of a hemi-parkinsonian mouse. / Park, Sunghee Estelle; Song, Kang Il; Kim, Hyungmin; Chung, Seok; Youn, Inchan.

In: Behavioural Brain Research, Vol. 344, 15.05.2018, p. 42-47.

Research output: Contribution to journalArticle

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abstract = "Recent studies have established methods for establishing a rodent model that mimics progressive stages of human Parkinson's disease (PD), via injection of graded doses of 6-hydroxydopamine (6-OHDA) into regions within the nigrostriatal pathway. However, the electrophysiological characteristics of the subthalamic nucleus (STN) in this model have not been fully elucidated in this model. This study aimed to investigate changes in the neuronal activity of the STN in a graded mouse model of PD. Increasing doses of 6-OHDA were unilaterally injected into the medial forebrain bundle (MFB) to produce a hemi-parkinsonian mouse model, mimicking early, moderate, advanced, and severe stages of human PD. Mice treated with higher doses of 6-OHDA demonstrated significantly lower rates of use of the impaired (contralateral) forelimb during wall contact, relative to sham mice. The STN firing rate was significantly increased in groups with >75{\%} dopaminergic cell loss in the substantia nigra pars compacta (SNc), whereas little increase was observed in groups with partial lesions of the SNc, relative to the sham group. In addition, firing patterns of the STN in groups treated with higher doses of 6-OHDA became more irregular and exhibited burst-like patterns of activity, with dominant slow wave oscillations in the frequency range of 0.3–2.5 Hz. Our results demonstrated a strong correlation between neuronal activities in the STN and dopamine depletion in the nigrostriatal pathway, which can be manipulated by variation of 6-OHDA doses.",
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