Dopamine-dependent corticostriatal synaptic filtering regulates sensorimotor behavior.

Area of Science:

• Neuroscience
• Synaptic Plasticity
• Motor Control

Background:

• Dopamine modulates corticostriatal activity essential for sensorimotor behaviors.
• Parkinson's disease involves nigrostriatal dopamine axon loss, treated with l-DOPA or D2 agonists, which can cause side effects.
• These therapies can lead to sensitized sensorimotor responses like dyskinesias and impulse control disorders.

Purpose of the Study:

• To investigate the role of D2, mGlu-R5, and CB1 receptors in corticostriatal synaptic filtering and sensorimotor behavior.
• To determine if modulating these receptors can normalize behavior in a Parkinson's disease mouse model.

Main Methods:

• Dopamine projections to the dorsal striatum were lesioned in mice.
• Unilateral sensorimotor deficits were assessed using the corridor test.
• Presynaptic corticostriatal activity was measured with the FM1-43 synaptic vesicle probe.

Main Results:

• D2 receptor activation filtered less active corticostriatal terminals, requiring mGlu-R5 and CB1 receptor co-activation in healthy mice.
• Lesioned mice showed deficits and overuse of the affected side after l-DOPA treatment.
• Combining l-DOPA or D2 agonists with a CB1 receptor antagonist normalized synaptic filtering and sensorimotor behavior.

Conclusions:

• Coordinated activation of D2, mGlu-R5, and CB1 receptors provides high-pass filtering of corticostriatal synapses.
• This filtering mechanism is crucial for normal sensorimotor responses to environmental cues.
• Targeting CB1 receptors alongside D2 agonists or l-DOPA may offer improved therapeutic strategies for Parkinson's disease.