The activity of neurons in motor areas of the cerebral cortex is reduced by the overall effect of the indirect pathway. This pathway involves inhibitory connections from the striatum to the external segment of the globus pallidus (GPe), which then sends inhibitory projections to the subthalamic nucleus and GPi. The subthalamic nucleus, in turn, sends an excitatory projection back to the GPi. In this pathway, GABA released from striatal terminals in the globus pallidus inhibits pallidal neurons in the external segment. The GPe normally releases GABA in the subthalamic nucleus, which inhibits the subthalamic neurons. Therefore, striatal inhibition of the GPe disinhibits neurons of the subthalamic nucleus. The subthalamic neurons, which are normally active, excite neurons in the GPi by releasing glutamate. When the subthalamic nucleus becomes more active due to disinhibition, it releases more glutamate in the GPi. This transmitter excites GPi neurons and activates inhibitory projections that affect the VA and VL thalamic nuclei. As a result, the activity of thalamic neurons and the cortical neurons they influence decreases.

The direct and indirect pathways have opposing actions. An increase in the activity of either pathway can lead to an imbalance in motor control, which is characteristic of basal ganglion diseases and can alter the motor output of the cortex.

Dopamine, the neurotransmitter used by neurons of the substantia nigra pars compacta, has an excitatory action on the direct pathway and an inhibitory action on the indirect pathway in the nigrostriatal pathway. However, dopamine's effect is modulatory, altering the response of striatal cells to other transmitters rather than directly triggering spikes. The different actions on the direct and indirect pathways result from the expression of different types of dopamine receptors (D1 and D2) by the spiny projection cells of the striatum involved in each pathway. D1 receptors are found on striatal cells projecting to the GPi in the direct pathway, while D2 receptors are found on striatal cells participating in the indirect pathway and projecting to the GPe. The overall consequence of dopamine release is the facilitation of activity in the motor areas of the cerebral cortex.

The striatum is subdivided into striosomes and matrix based on associated neurotransmitters. The matrix area receives cortical projections related to motor control, while the limbic system projects to the striosomes. Striosomes are believed to synapse in the pars compacta of the substantia nigra and influence the dopaminergic nigrostriatal pathway.

The basal ganglia have a significant influence on the lateral system of motor pathways, which is consistent with movement disorders observed in basal ganglia diseases. However, the basal ganglia also regulate the medial motor pathways, as diseases of the basal ganglia can affect the posture and tone of proximal muscles.
The overall effect of the indirect pathway is to reduce the activity of neurons in motor areas of the cerebral cortex. The indirect pathway involves inhibitory connections from the striatum to the external segment of the globus pallidus (GPe), which in turn sends an inhibitory projection to the subthalamic nucleus and to the GPi. The subthalamic nucleus then sends an excitatory projection back to the GPi (see
Fig. 9.25A
In this pathway, pallidal neurons in the external segment are inhibited by the GABA released from striatal terminals in the globus pallidus. The GPe normally releases GABA in the subthalamic nucleus and thereby inhibits the subthalamic neurons. Therefore, striatal inhibition of the GPe results in the disinhibition of neurons of the subthalamic nucleus. The subthalamic neurons are normally active, and they excite neurons in the GPi by releasing glutamate. When the neurons of the subthalamic nucleus become more active because of disinhibition, they release more glutamate in the GPi. This transmitter excites neurons in the GPi and consequently activates inhibitory projections that affect the VA and VL thalamic nuclei. The activity of the thalamic neurons consequently decreases, as does the activity of the cortical neurons that they influence.
The direct and indirect pathways thus have opposing actions; an increase in the activity of either one of these pathways might lead to an imbalance in motor control. Such imbalances, which are typical of basal ganglion diseases, may alter the motor output of the cortex.
CHAPTER 9 Organization of Motor Function
Actions of Neurons in the Pars Compacta of the Substantia Nigra on the Striatum
Dopamine is the neurotransmitter used by neurons of the substantia nigra pars compacta. In the nigrostriatal pathway, release of dopamine has an overall excitatory action on the direct pathway and an inhibitory action on the indirect pathway. This is, however, a modulatory type of effect; that is, dopamine is apparently causing its action not by triggering spikes directly but rather by altering the striatal cells’ response to other transmitters. The different actions on the direct and indirect pathways result from the expression of different types of dopamine receptors (D1 and D2) by the spiny projection cells of the striatum that contribute to the direct and indirect pathways. D1 receptors are found on striatal cells that form the direct pathway by projecting to the GPi, whereas D2 receptors are found on striatal cells that participate in the indirect pathway and project to the GPe. The overall consequence of dopamine release in both cases is facilitation of activity in the motor areas of the cerebral cortex.
Subdivision of the Striatum Into Striosomes and Matrix
On the basis of the associated neurotransmitters, the stria-tum has been subdivided into zones called striosomes and matrix. The cortical projections related to motor control end in the matrix area. The limbic system projects to the striosomes. Striosomes are thought to synapse in the pars compacta of the substantia nigra and to influence the dopaminergic nigrostriatal pathway.
Role of the Basal Ganglia in Motor Control
The basal ganglia influence the cortical motor areas. Therefore, the basal ganglia have an important influence on the lateral system of motor pathways. Such an influence is consistent with some of the movement disorders observed in diseases of the basal ganglia. However, the basal ganglia must additionally regulate the medial motor pathways because diseases of the basal ganglia can also affect the posture and tone of proximal muscles.