basal ganglia pathway (direct and indirect)

[howto]

hi,
I'm kinda confused about the basal ganglia (direct and indirect pathway). Can someone please explain them in term of clinical disorders. thank you very much.

[Anonymous]

Here is the short and long answer. First the short....

The direct pathway is thought to facilitate movements while the indirect pathway is thought to inhibit unwanted movements.

Now the long....

http://www.mbfys.kun.nl/mbfys/education/medical/webteach/dental/coo_2003/coo_motoriek/basale%20ganglia/baargad.jpg
DeLong model of basal ganglia.
Black lines ending in triangles represent excitatory connections (glutamate). Gray lines ending in squares represent inhibitory connections (GABA). Dashed gray lines represent dopaminergic connections.
Str: striatum; GPe: globus pallidus externa; GPi: globus pallidus interna; STN: subthalamic nucleus; SNc: substantia nigra pars compacta; SNr: substantia nigra pars reticulata; D1 and D2: dopamine type 1 and type 2 receptors.


DELONG MODEL FOR BASAL GANGLIA FUNCTION

The DeLong model of basal ganglia function (Figure 1) is inspired by the dominant anatomical connections of basal ganglia nuclei and their neurotransmitters.


Direct and Indirect pathway

The basal ganglia comprise five nuclei (caudate, putamen, globus pallidus, substantia nigra, and subthalamic nucleus). The globus pallidus is further subdivided into the globus pallidus externa (Gpe) and globus pallidus interna (Gpi). The caudate and putamen together are called the striatum or neostriatum. The model suggests that there are two pathways through the basal ganglia - Direct and Indirect. Both pathways begin in the cortex and both pathways converge on the globus pallidus interna, the main outflow of the basal ganglia. The direct pathway is thought to facilitate movements while the indirect pathway is thought to inhibit unwanted movements.

Direct Pathway

The direct pathway begins with projections from the cortex to the striatum. One population of striatum neurons projects directly to the Gpi. The Gpi projects to the thalamus which then projects back to the cortex. The connections from the cortex to the striatum use glutamate and are excitatory. The connections from the striatum to the Gpi use GABA as their neurotransmitter and are inhibitory, just like the connections from Gpi to the thalamus. The connections from the thalamus back to the cortex are excitatory. The cortex excites the striatum which then inhibits the Gpi through the direct pathway. The Gpi is normally tonically active and inhibitory to the thalamus. When the Gpi is inhibited, the thalamus is relieved from inhibition (this is called disinhibition) and excites the cortex, thereby reinforcing the desired movement.


Indirect Pathway

In the indirect pathway a separate group of striatal neurons projects to Gpe. Gpe then projects to the subthalamic nucleus (STN). The subthalamic nucleus projects to Gpi. The Gpi projects to ventolateral thalamus and the thalamus projects back to the cortex. The projections from the striatum to the Gpe use GABA and are inhibitory. The projections from the Gpe to the subthalamic nucleus also use GABA and are also inhibitory. The projection from the subthalamic nucleus to the Gpi is excitatory. Therefore, the cortex excites the striatum which then inhibits Gpe. Since Gpe is inhibitory to the subthalamic nucleus, the subthalamic nucleus now becomes more active and excites the Gpi. The Gpi being more active, then inhibits the thalamus and the thalamus does not excite the cortex. In this way, activation of the indirect pathway by the striatum causes a relative inhibition of movement.

Summary of DeLong model

The opponent parallel pathway hypothesis emphasizes two major paths of information flow from the striatum to the basal ganglia output nuclei: GPi and SNr. One is an inhibitory direct pathway from the striatum to the GPi/SNr. The other is an effectively excitatory indirect pathway from the striatum to the GPe (inhibitory), from the GPe to the STN (inhibitory), and from the STN to the GPi/SNr (excitatory). This hypothesis maintains that the two pathways are in balance such that increased activity in the direct pathway causes decreased GPi/SNr output, and increased activity in the indirect pathway causes increased GPi/SNr output. By adjusting the balance, the cortical targets of the basal ganglia can be facilitated or inhibited. The hypothesis predicts that abnormally decreased output results in excessive movement (chorea) and abnormally increased output results in decreased movement (Parkinson disease). The primary evidence for this hypothesis is the finding that activity in the STN and GPi is increased in parkinsonian monkeys but decreased in monkeys with chorea.

ref: mbfys.kun.nl