Nigrostriatal Pathway

The nigrostriatal pathway is one of the four major dopamine pathways in the brain. It originates in the substantia nigra, specifically the pars compacta region, and extends to the dorsal striatum, which includes the caudate nucleus and the putamen^[1].

The neurons in the substantia nigra pars compacta (SNc) synthesise dopamine, which is then sent via axons through the nigrostriatal pathway to the striatum. This dopamine transmission plays a pivotal role in the modulation and control of movements^[2].

The nigrostriatal pathway is largely associated with motor planning, reward seeking behaviour, and other functions related to movement. It has a direct role in the initiation and execution of voluntary movements and has been heavily implicated in movement disorders^[3].

The dopaminergic neurons of the substantia nigra pars compacta release dopamine into the striatum. In the striatum, dopamine acts on D1 and D2 type dopamine receptors, which have opposing effects^[5].

The activation of D1 receptors (direct pathway) enhances the excitatory effect on the basal ganglia output structures (GPi and SNr). Conversely, D2 receptors (indirect pathway) reduce the inhibitory effect on these structures. This intricate system allows for the delicate balance of movement facilitation and inhibition, and thus, the efficient initiation and control of voluntary movements^[6].

Initiation: The process begins in the cerebral cortex, specifically in the premotor and motor areas, where an intention to make a voluntary movement is generated. These cortical areas then send excitatory signals via glutamatergic neurons to the striatum, signaling the type of movement that's intended^[3].

Signal Transmission: The striatum, receiving these signals, processes the information and, based on the inhibitory GABAergic medium spiny neurons, sends inhibitory signals to two primary output nuclei of the basal ganglia: the internal segment of the globus pallidus (GPi) and the substantia nigra pars reticulata (SNr)^[7].

Dopamine Modulation: This is where the nigrostriatal pathway's critical role comes into play. The substantia nigra pars compacta (SNc), which is the starting point of the nigrostriatal pathway, releases dopamine to the striatum^[5].

• Dopamine, upon binding to D1 receptors in the striatum (part of the direct pathway), promotes the thalamus's activity by inhibiting the inhibitory influence on the thalamus (a phenomenon referred to as disinhibition)^[8].

• Dopamine, upon binding to D2 receptors in the striatum (part of the indirect pathway), suppresses the thalamus's activity by enhancing the inhibitory influence on the thalamus^[6].

This dopaminergic modulation provided by the nigrostriatal pathway helps balance the activities of the direct and indirect pathways, which is crucial for coordinating and executing smooth and precise movements^[9].

Output: The GPi and SNr, as primary output nuclei, send inhibitory signals to specific thalamic nuclei, mainly the ventral anterior and ventral lateral nuclei, which are inherently excitatory^[7].

Final Pathway: From here, the thalamus sends excitatory signals back to the motor areas of the cerebral cortex, completing a loop known as the cortico-basal ganglia-thalamo-cortical loop^[8].

Execution: Based on these signals, the cortex finally executes the desired motor action through the corticospinal tract and other descending motor pathways^[10].

The nigrostriatal pathway, through its modulation of dopamine release and subsequent effects on striatal activity, plays a key role in the overall motor control mechanism by fine-tuning the balance between movement initiation (facilitation) and suppression (inhibition)^[6].