Parkinson's disease is characterized by the destruction and loss of pigment of the substania nigra, the site of dopamine production, and marked decreased amounts of dopamine at the caudate (Marsden, 948). Normally, the substantia nigra appears black; however, with PD, this pigment is lost .
As seen in the previous figure, the net effect of the corto-basal ganglia loop is excitatory. With the decreased production of dopamine, the overall pathway is depressed and consequently, it does not exert its normal effects and the symptoms associated with PD are expressed. More specifically, there is decreased innervation of the caudate; consequently, there is increased inhibition at the globus pallidus, which results in hyperkinesis. In particular, the excitatory signal from the subthalamic nucleus that innervates the internal globus pallidus is decreased (Black, 70-71). Consequently, tremors, rigidity, as well as the other symptoms of PD are seen. In short, with reduced amounts of dopamine, the excitatory signal sent to the motor cortex is replaced with an inhibitory one.
Depicted below is the overall schematic for PD: (Black, 71)
As a result of the death of pigmented substantia nigra neurons, dopamine content at the caudate and the putamen is reduced by 80% or more in people with PD (Marsden, 949) . The estimated loss of neurons in the substantia nigra is 1% per year, or 10 neurons per day, in patients with PD. In contrast, this death rate is 0.5% in normal people (Agid, 1321). Moreover, statistical analysis indicates that PD symptoms are shown when a dopaminergic neural loss has reached critical numbers: 70-80% at the caudate and putamen, 50-60% in the substantia nigra (Agid, 1322) .
Although there is widespread damage to dopaminergic neurons, other neural systems are also affected. These include noradrenergic, serotonergic, and cholinergic systems that project to the cortex and limbic structures. As a result, there is pervasive cortical damage. In 50% of PD cases, there are cortical damage showing Alzheimer-like pathology (Agid, 1322).