Direct Pathway Activation in Parkinson's Disease Model
Objective: To directly activate basal ganglia circuitry using optogenetic control of direct- and indirect-pathway medium spiny projection neurons to assess motor behavior regulation and rescue of parkinsonian motor deficits in a mouse model of Parkinson's disease
This is a Direct Pathway Activation in Parkinson's Disease Model protocol using mouse as the model organism. The procedure involves 6 procedural steps, 2 equipment items, 1 materials. Extracted from a 2010 paper published in Nature.
Model and subjects
mouse • D1-Cre and D2-Cre BAC transgenic mice • Not specified • Not specified • Not specified • Not specified
Study window
Estimated timing pending
Core workflow
Viral vector preparation and injection • Stereotactic injection into striatum • Optogenetic stimulation of indirect-pathway MSNs
Primary readouts
- Freezing behavior
- Bradykinesia (slow movement)
- Locomotor initiation
- Locomotion/locomotor activity
Key equipment and reagents
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Protocol Steps
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Viral vector preparation and injection
Prepare Cre-dependent viral expression vectors containing channelrhodopsin-2 for injection into striatum
Note: Vectors designed for Cre-dependent expression in D1-Cre and D2-Cre transgenic mice
View evidence from paper
“Cre-dependent viral expression of channelrhodopsin-2 in the striatum of D1-Cre and D2-Cre BAC transgenic mice”
Stereotactic injection into striatum
Inject Cre-dependent channelrhodopsin-2 viral vectors into the striatum of transgenic mice
Note: Bilateral injection for bilateral excitation experiments
View evidence from paper
“Cre-dependent viral expression of channelrhodopsin-2 in the striatum of D1-Cre and D2-Cre BAC transgenic mice”
Optogenetic stimulation of indirect-pathway MSNs
Bilaterally excite indirect-pathway medium spiny projection neurons using optogenetic control
Note: Elicits parkinsonian state characterized by increased freezing, bradykinesia, and decreased locomotor initiations
View evidence from paper
“Bilateral excitation of indirect-pathway MSNs elicited a parkinsonian state, distinguished by increased freezing, bradykinesia, and decreased locomotor initiations”
Optogenetic stimulation of direct-pathway MSNs
Activate direct-pathway medium spiny projection neurons using optogenetic control
Note: Reduces freezing and increases locomotion in normal mice
View evidence from paper
“activation of direct-pathway MSNs reduced freezing and increased locomotion”
Direct pathway activation in Parkinson's disease model
Activate direct-pathway circuitry in mouse model of Parkinson's disease to assess rescue of motor deficits
Note: Complete rescue of freezing, bradykinesia, and locomotor initiation deficits observed
View evidence from paper
“In a mouse model of Parkinson's disease, direct pathway activation completely rescued deficits in freezing, bradykinesia, and locomotor initiation”
Behavioral assessment
Measure motor behaviors including freezing, bradykinesia, and locomotor initiation during optogenetic stimulation
Note: Behaviors assessed during direct and indirect pathway activation
View evidence from paper
“Bilateral excitation of indirect-pathway MSNs elicited a parkinsonian state, distinguished by increased freezing, bradykinesia, and decreased locomotor initiations”