Indirect pathway of the basal ganglia (Indirect pathway)

The indirect pathway of the basal ganglia is a multi-synaptic neural circuit that plays a critical role in motor control by inhibiting movement (StatPearls, 2023). It begins with the projection of GABAergic medium spiny neurons from the striatum to the globus pallidus externa (GPe); these neurons specifically express dopamine D2 receptors (Nature Reviews Neuroscience, 2010). The circuit continues from the GPe to the subthalamic nucleus (STN), which then provides excitatory glutamatergic input to the globus pallidus interna (GPi) and substantia nigra pars reticulata (SNr). Increased activity in this pathway leads to greater inhibition of the thalamus, thereby reducing excitatory drive to the motor cortex and suppressing movement (Wikipedia, 2024). In Parkinson's disease, the depletion of dopamine leads to the disinhibition and overactivity of the indirect pathway, contributing to symptoms like bradykinesia and rigidity (Movement Disorders, 2015). Conversely, underactivity of this pathway is associated with hyperkinetic disorders such as Huntington's disease. Therapeutic strategies often involve dopamine D2 receptor agonists to reduce the pathway's activity or surgical interventions like Deep Brain Stimulation (DBS) targeting the STN to modulate the circuit's output. Pharmacological agents like antipsychotics act as D2 antagonists, which can inadvertently increase indirect pathway activity, leading to extrapyramidal side effects.

Other names

Striatopallidal pathwayD2-mediated pathwayIndirect motor loop

Modulation of dopamine D2 receptors on striatal medium spiny neurons to regulate the inhibitory output of the basal ganglia circuit, thereby influencing motor suppression.