Indirect Pathway
Published: Jul 17, 2023
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Updated: Aug 7, 2023
Written by Oseh Mathias
Founder, SpeechFit
The indirect pathway, also referred to as the indirect basal ganglia pathway, is a neural circuit in the brain that helps to control movement[1]. It's often described in contrast to the direct pathway. While the direct pathway facilitates desired movement, the indirect pathway inhibits or reduces unwanted or unnecessary movement, thus contributing to overall movement control and coordination[2].
The indirect pathway is often referred to as the "no-go" pathway, as it's primarily involved in suppressing undesired or inappropriate motor actions[3]. It works to inhibit the thalamus and thereby decrease motor activity[4].
Here's the general sequence of events in the indirect pathway:
The cerebral cortex sends excitatory signals (using the neurotransmitter glutamate) to the striatum, which is the input nucleus of the basal ganglia[6].
In the striatum, the received excitatory signals then trigger inhibitory signals (using the neurotransmitter GABA) to the external part of the globus pallidus (GPe)[7].
The GPe, which is usually inhibitory to the subthalamic nucleus (STN), decreases its inhibition due to the inhibitory signals received from the striatum[8].
This decreased inhibition from the GPe allows the STN to send excitatory signals (via glutamate) to the internal part of the globus pallidus (GPi) and the substantia nigra pars reticulata (SNr)[9].
The GPi and SNr, being the output nuclei of the basal ganglia, respond to the excitation from the STN by increasing their inhibitory output (via GABA) to the thalamus[10].
This increased inhibition from the GPi/SNr to the thalamus prevents the thalamus from sending excitatory signals to the cerebral cortex[11].
As a result, the motor cortex is less activated and the initiation of motor movements is suppressed[12].
The indirect pathway of the brain can be suppressed by dopamine, a neurotransmitter, released from a region called the substantia nigra[13]. The dopamine binds to the D2 dopamine receptor present on the neurons in the striatum, a key area involved in the indirect pathway[14]. This binding event has an inhibitory effect. As a result, the inhibitory neurons in the striatum, which are part of the indirect pathway, are themselves inhibited[15]. This creates a "disinhibition" of the external part of the globus pallidus (GPe) neurons, leading to suppression of the excitatory neurons in the subthalamic nucleus[16]. This sequence of events leads to a decrease in the inhibition of the thalamus, thereby increasing its output to the cortex[17].
Disorders of the basal ganglia, which includes dysfunction in the indirect pathway, are typically categorised as movement disorders[18]. These disorders often involve an imbalance between the direct and indirect pathways, which respectively promote and suppress movement[19].
Oseh is a software engineer, entrepreneur and founder of SpeechFit. Oseh is passionate about improving health and wellbeing outcomes for neurodiverse people and healthcare providers alike.
References
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