creates an overall net excitatory effect on the thalamus and on movement generated by the motor cortex. Indirect pathway of movement The indirect pathway is involved in suppressing unwanted movement. The projections from dopamine D2 receptors containing medium spiny neurons in the caudate nucleus and putamen synapse onto tonically active GABAergic cells in the external segment of the globus pallidus (GPe), which then projects to the substantia nigra pars reticulata via the excitatory subthalmic nucleus (STN). Because the striatopallidal and nigrothalamic pathways are inhibitory but the subthalamic to nigra pathway is excitatory, activation of the indirect pathway creates an overall net inhibitory effect on the thalamus and on movement by the motor cortex. Clinical significance Parkinson's disease Parkinson's disease is characterized by severe motor problems, mainly hypokinesia, rigidity, tremors, and postural imbalance. Loss of dopamine neurons in the nigrostriatal pathway is one of the main pathological features of Parkinson's disease. Degeneration of dopamine producing neurons in the substantia nigra pars compacta and the putamen-caudate complex leads to diminished concentrations of dopamine in the nigrostriatal pathway, leading to reduced function and the characteristic symptoms. The symptoms of the disease typically do not show themselves until 80-90% of dopamine function has been lost. Another hypothesis suggests that Parkinson's disease is an imbalance between dopamine (D.A.) and acetylcholine (ACh) in the dorsal striatum, and not just dopamine deficiency. Levodopa-induced dyskinesia Levodopa-induced dyskinesias (LID) is a complication associated with long-term use of the Parkinson's treatment L-DOPA, characterized by involuntary movement and muscle contractions. This disorder occurs in up to 90% of patients after 9 years of treatment. The use of L-DOPA in patients can lead to interruption of nigrostriatal dopamine projections as well as changes in the post-synaptic neurons in the basal ganglia. Schizophrenia Presynaptic dopamine metabolism is altered in schizophrenia. Other dopamine pathways Other major dopamine pathways include: mesocortical pathway mesolimbic pathway tuberoinfundibular pathway See also Dopamine Parkinson's disease Stuttering References External links Diagram Central nervous system pathways Dopamine Basal ganglia connections