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Translational approach to apathy-like behavior in mice: From the practical point of view
Kenji F Tanaka1, Takuya Hamaguchi2
1Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
Abstract:
Apathy is a pervasive clinical phenomenon that deserves more attention at the translational and pre-clinical levels. To study apathy-like behavior in mice, we relied on an operational definition of apathy: the quantitative reduction of voluntary, goal-directed behaviors. We recently found that the chronic loss of function of a specific cell type (striatal dopamine receptor type 2-expressing medium spiny neurons, D2-MSN) in a restricted region (the ventrolateral striatum, VLS) was sufficient to induce apathy-like behavior in a food-seeking operant task. We further showed that VLS D2-MSN are activated at the preparatory period, and that optogenetic inhibition of VLS D2-MSN during that period resulted in transient decreases in instrumental motivation, strengthening the hypothesis that VLS D2-MSN mediate apathy-like behavior in mice. Mice bearing VLS D2-MSN dysfunction can thus be regarded as an apathy model for future translational studies.
Insights
Researchers identified a specific brain cell type, ventrolateral striatum dopamine receptor type 2-expressing medium spiny neurons (VLS D2-MSN), whose dysfunction causes apathy-like behavior in mice. This finding offers a new preclinical model for studying apathy.
Area of Science:
- Neuroscience
- Behavioral Science
Background:
- Apathy is a common clinical symptom requiring further preclinical investigation.
- Apathy is operationally defined as a reduction in voluntary, goal-directed behaviors.
Purpose of the Study:
- To investigate the role of specific neuronal populations in mediating apathy-like behavior.
- To establish a preclinical model for apathy research.
Main Methods:
- Investigated the effects of chronic loss of function in ventrolateral striatum dopamine receptor type 2-expressing medium spiny neurons (VLS D2-MSN) in mice.
- Utilized an operant task to quantify food-seeking behavior.
- Employed optogenetics to inhibit VLS D2-MSN during the preparatory period.
Main Results:
- Chronic dysfunction of VLS D2-MSN was sufficient to induce apathy-like behavior in mice.
- VLS D2-MSN are activated during the preparatory phase of goal-directed actions.
- Optogenetic inhibition of VLS D2-MSN transiently reduced instrumental motivation.
Conclusions:
- VLS D2-MSN play a crucial role in mediating apathy-like behavior.
- Mice with VLS D2-MSN dysfunction serve as a valid preclinical model for apathy.
- This model can facilitate future translational studies on apathy.
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