314 Neuroanatomy: Draw It to Know It
Direct & Indirect Pathways: Circuitry
Here, we will draw a fl ow diagram for the circuitry of
the direct and indirect pathways; they involve medium
spiny neuron projections from the striatum to the globus
pallidus and substantia nigra. Th e direct and indirect
pathways are the best described of the numerous frontal-
subcortical pathways that project through the basal gan-
glia. First, label the cerebral cortex, thalamus, and motor
neurons. Th en, show that the thalamus excites the cere-
bral cortex, which stimulates the motor neurons. Next,
we will draw the direct pathway. Label the striatum — the
combined caudate and putamen. Now, show that the
cortex excites the striatum. Within the striatum, the sen-
sorimotor cortex primarily targets the putamen; the
putamen is the primary source of the direct and indirect
pathways. Next, label the combined globus pallidus
internal segment and the substantia nigra reticulata; they
comprise the fi nal output nuclei of the basal ganglia —
hereaft er, we consider them as a single functional entity:
GPi/STNr. Next, show that the striatum inhibits the
GPi/STNr and then show that the GPi/STNr inhibits
the thalamus. Th us, indicate that the direct pathway is
overall excitatory.
Now, we will draw the indirect pathway. First, include
the globus pallidus external segment; show that it is
inhibited by the striatum and then show that the globus
pallidus external segment inhibits the GPi/STNr — thus,
indicate that the indirect pathway is overall inhibitory.
A parallel circuit also exists within the indirect pathway
that passes through the subthalamic nucleus. So, now,
add the subthalamic nucleus and show that it excites the
GPi/STNr; then, show that the globus pallidus external
segment inhibits the subthalamic nucleus. Th erefore,
whether it is because of the globus pallidus external
segment inhibition of the GPi/STNr or because of
the globus pallidus external segment inhibition of the
subthalamic nucleus, through both means, the end result
of the indirect pathway is that it is overall inhibitory. As
a clinical corollary, when the subthalamic nucleus is
selectively injured, patients develop wild ballistic, fl ing-
ing movements, called hemiballismus, on the side con-
tralateral to the subthalamic nucleus lesion due to a loss
of motor inhibition.
Lastly, we need to account for the role of the substan-
tia nigra compacta in the direct and indirect pathways.
Parkinson’s disease results from loss of dopaminergic cells
within the substantia nigra compacta, and in Parkinson’s
disease, there is muscle rigidity, stiff ness, diffi culty with
initiation of movement, and slowness and decomposition
of rapid alternating movements. In our fl ow diagram,
near the striatum, label the substantia nigra compacta,
and indicate that it releases dopamine. If dopamine acted
equally on both the direct and indirect pathways, the
two pathways would equalize one another and the net
eff ect would be nil. So, now, show that the two most
prominent striatal dopamine receptors are the dop-
amine 1 receptor, which is part of the direct pathway
and is excited by dopamine, and the dopamine 2 recep-
tor, which is part of the indirect pathway and is inhib-
ited by dopamine. Th us, dopamine from the substantia
nigra compacta excites the direct pathway and inhibits
the indirect pathway — both of these eff ects promote
movement.
Note that many frontal-subcortical pathways project
through the basal ganglia in addition to the motor path-
ways we have drawn; these pathways help drive a multi-
tude of processes, including emotional, behavioral,
somatosensory, and cognitive functional modalities.
Th rough the corticostriatal fi bers — the Muratoff bundle
and the external capsule — the cerebral cortex targets the
striatum in a topographic manner. For instance, the pre-
frontal cortex acts through innervation of the head and
body of the caudate nucleus; the parietal lobes act through
innervation of both the putamen and caudate; the pri-
mary auditory cortex projects to the caudoventral puta-
men and tail of the caudate; and the visual cortices project
primarily to the nearest portion of the caudate nucleus.