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expert reviews
in molecular medicine

Basal ganglia circuitry in Parkinson’s disease

Cortex

Glutamate Glutamate Glutamate

Putamen

Indirect
pathway Dopamine

Enk
GABA Direct
SNc pathway Thalamus

GPe GABA
SP

GABA

GPi
GABA
STN SNr
Glutamate

Excitatory
Inhibitory PPN

Basal ganglia circuitry in Parkinson’s disease

Expert Reviews in Molecular Medicine C 2003 Cambridge University Press

Figure 3. Basal ganglia circuitry in Parkinson’s disease. In Parkinson’s disease (PD), the natural balance
of the circuit shown in Figure 2 is lost owing to the depletion of dopamine in the striatum. Both the direct and
indirect pathways operate through the GPi/SNr output nuclei and their influence is inhibitory on the thalamus.
Thus, increased activity in the output nuclei leads to increased inhibition on the glutamatergic excitation of the
motor cortex and a subsequent reduction in movement, observed in patients as bradykinesia. In addition,
other structures such as the pedunculopontine nucleus (PPN) receive an abnormal input from the basal ganglia,
which contribute to some of the clinical signs, such as gait disturbance. These changes in the PD brain are
shown here by the differing thickness of arrows, which represents the relative degree of activation in each
projection. Abbreviations: Enk, enkephalin; GABA, gamma-aminobutyric acid; GPe, globus pallidus, external
segment; GPi, globus pallidus, internal segment; SNc, substantia nigra pars compacta; SNr, substantia nigra
pars reticulata; SP, substance P; STN, subthalamic nucleus (fig003rbc).

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Accession information: Vol. 5; 28 March 2003
©2003 Cambridge University Press