Substantia Nigra

Substantia nigra is a relatively small yet very important structure in human brain. It is a motor nucleus present in the midbrain. Substantia nigra plays an important role in the regulation of movements. The brain lesions that affect substantia nigra can cause a number of movement disorders including Parkinson’s disease and other dyskinesias. It is also clinically significant in the pathogenesis of schizophrenia.

In this article, we will study different aspects of substantia nigra, its anatomical features, its functions and clinical significance. You will gain a considerable knowledge after reading this educational article. So, keep reading!

Anatomical Features

Under this heading, we will discuss the location of substantia nigra, its parts, the cells present in it, and input and output fibers connecting it to other areas of brain.


Substantia nigra is a part of midbrain, the top most structure present in the brain stem. It is present in the anterior part of midbrain in the cerebellar peduncles. Substantia nigra divides the cerebellar peduncles into anterior crus cerebri and posterior tegmentum of mid brain.

Anatomically it is present in the midbrain. However, function-wise substantia nigra is considered to be a part of basal ganglia.


Substantia nigra is divided into two parts; pars reticulata and pars compacta. Sometimes, a third region called pars lateralis is also mentioned. However, it is mostly considered a part of pars reticulata

Pars Reticulata

It is also called pars reticularis. It is present anterior to pars compacta in the cerebellar peduncles. It has structural similarity to the globus pallidus present in the basal ganglia. The neurons present in pars reticulata are all GABAergic neurons. That is why, it is considered to be a part of globus pallidus physiologically.

Pars Compacta

It is present posterior and medial to pars reticulata in the cerebellar peduncles of midbrain. It composed of mainly dopaminergic neurons. This part of substantia nigra is mainly associated with the pathogenesis of the Parkinson’s disease. 

Input fibers

Both parts of substantia nigra receive input or afferent fibers from different regions of brain.

Afferent to Pars Reticulata

This part of substantia nigra receives afferent fibers mainly form the striatum of basal ganglia. The input fiber come via two pathways; direct pathway and indirect pathway.

In case of direct pathway, the inhibitory GABAergic fibers directly reach the pars reticulata from the striatum.

In case of indirect pathway, the GABAergic fibers from the striatum project to the globus pallidus. The GABAergic fibers from the globus pallidus reach the subthalamic nuclei. Later, the stimulatory glutaminergic fibers from the subthalamic nuclei synapse with the neurons in pars reticulata.

Afferent to Pars Compacta

This part of substantia nigra also receives GABAergic fibers from the globus pallidus of basal ganglia. It also receives inhibitory GABAergic fibers from pars reticulata.

Output fibers

The two parts of substantia nigra send efferent fibers to different areas of brain.

Efferent fibers from Pars Reticulata

Pars reticulata sends efferent fibers mainly to the thalamus. These are the inhibitory GABAergic fibers. It also sends efferent fibers to pars compacta in order to regulate the release of dopamine.

Efferent fibers from Pars Compacta

The efferent fibers of pars compacta are dopaminergic fibers that project to striatum of basal ganglia. Here, they release dopamine that regulates the activation of direct and indirect pathways. Some of the dopaminergic fibers also project to the limbic system of brain.

Functions of Substantia Nigra

Substantia nigra is a very important structure in brain that plays a key role in the regulation of muscle tone and movements. In this section of the article, we will discuss the functions of two parts of substantia nigra separately.

Functions of Pars Reticulata

It is an important processing center that processes the GABA signals. It is a part of both direct and indirect pathways. It sends GABAergic fibers to thalamus that inhibit the thalamic neurons.  

In case of direct pathway activation, the GABAergic fibers coming straight from the striatum inhibit the neurons in the pars reticulata. As a result, there GABAergic fibers from the pars reticulata to thalamus are inhibited. This causes increased firing thalamic neurons and movement results.

The indirect pathway tends to inhibit the movements. In this case, the glutaminergic fibers from the subthalamic nuclei stimulate the GABAergic neurons in the pars reticulata. These GABAergic neurons, in turn, inhibit the neurons in the thalamus. The decreased thalamic firing tends to inhibit the movements.

The GABAergic fibers of pars reticulata also control the release of dopamine by internal connections to pars compacta. These connections tend to inhibit the dopamine release.

Functions of Pars Compacta

Pars compacta is the most important structure of midbrain that is involved in the motor control of the body. It sends efferent fibers to the striatum that release dopamine neurotransmitter.

There are two types of dopamine receptors in striatum; D1 receptors and D2 receptors.

The D1 receptors are the excitatory receptors, present in the direct pathway. The excitation of these receptors promotes the activation of direct pathway and movements result.

The D2 receptors are the inhibitory receptors present in the indirect pathway. Their excitation results in inhibition of the indirect pathway which further promotes movements.

Pars compacta also plays a significant role in the learning of responses to particular stimuli. It is also involved in the process of spatial learning.

It has also been found that pars compacta is involved in the regulation of sleep cycle and REM sleep.

Clinical Significance

Substantia nigra plays an important part in the pathogenesis of a number of diseases affecting movements, behavior memory and learning. Following are some of the clinically significant conditions associated with substantia nigra.

Parkinson’s Disease

It is the most important clinical condition associated with the substantia nigra. In Parkinson’s disease, there is degeneration of neurons in the substantia nigra, mainly in pars compacta. It results in decreased release of dopamine in the corpus striatum, leading towards the hypersensitivity of dopamine receptors in the striatum.

This disease is of unknown origin and affects the people between the ages of 45 and 55 years. The patients of Parkinson’s disease present the following characteristic symptoms:

  • Tremors: The alternating contractions of agonists and antagonists result in tremors. The tremors are seen in hands. They occur even when a person is not performing any movement and are called resting tremors.
  • Rigidity: A specific type of rigidity is present. It is resistance to the passive movements. If the tremor is absent, it is called plastic rigidity. However, if the tremor is resent, the rigidity is overcome in a series of jerks. This type of rigidity is called cogwheel rigidity.
  • Bradykinesia: There is difficulty to initiate any movement. 
  • Postural disturbance: The patient acquires a characteristic posture with flexed arms and a stoop. While walking, he or she takes small steps.


While decreased level of dopamine cause Parkinson’s disease, its increased levels in brain can cause schizophrenia. This forms the basis of using dopamine antagonists in the treatment of schizophrenia and other psychotic disorders.

The dopamine hypothesis of schizophrenia states that it is due to excessive release of dopamine in the limbic system. This dopamine is released by the dopaminergic mesolimbic fibers, arising from pars compacta of the substantia nigra.

Based on this dopamine hypothesis of schizophrenia, the typical antipsychotics, which are the dopamine antagonists, are successfully used in the treatment of schizophrenia.


Substantia nigra is a large motor nucleus present in the midbrain. It is a part of brain stem and is present in the cerebellar peduncles of midbrain.

Structurally, it is present in midbrain, but functionally; it is considered to be a part of basal ganglia.

Substantia nigra comprises of two structural components; pars reticulata and pars compacta.

Pars reticulata mainly consists of GABAergic neurons and is considered a part of globus pallidus. It receives afferent fibers from striatum via direct and indirect pathways. The efferent fibers from pars reticulata mainly go to the thalamus. The output fibers are GABAergic.

Pars compacta, present posterior and medial to pars reticulata, consists of dopaminergic neurons. It receives afferent GABAergic fibers from globus pallidus and pars reticulata. The output fibers from pars compacta reach striatum and the limbic system. These are dopaminergic fibers.

The main function of substantia nigra is the motor control which is manifested by both pars compacta and pars reticulata. The other functions performed by pars compacta include spatial learning and regulation of sleep cycle. It also regulates the REM sleep.

Clinically significant medical conditions associated with substantia nigra include Parkinson’s disease and Schizophrenia.

Parkinson’s disease is due to the destruction of neurons in pars compacta resulting in decreased dopamine release at striatum.

Schizophrenia is considered to be due to excessive dopamine in the limbic system released by the dopaminergic fibers form pars compacta.


  1. Hikosaka O, Wurtz RH (May 1983). “Visual and oculomotor functions of monkey substantia nigra pars reticulata. III. Memory-contingent visual and saccade responses”. Journal of Neurophysiology. 49 (5): 1268–84. doi:10.1152/jn.1983.49.5.1268PMID 6864250.
  2. Tseng KY, Riquelme LA, Belforte JE, Pazo JH, Murer MG (January 2000). “Substantia nigra pars reticulata units in 6-hydroxydopamine-lesioned rats: responses to striatal D2 dopamine receptor stimulation and subthalamic lesions”. The European Journal of Neuroscience. 12 (1): 247–56. doi:10.1046/j.1460-9568.2000.00910.xPMID 10651879.
  3. Deransart C, Hellwig B, Heupel-Reuter M, Léger JF, Heck D, Lücking CH (December 2003). “Single-unit analysis of substantia nigra pars reticulata neurons in freely behaving rats with genetic absence epilepsy”. Epilepsia. 44 (12): 1513–20. doi:10.1111/j.0013-9580.2003.26603.xPMID 14636321.
  4. Hodge GK, Butcher LL (August 1980). “Pars compacta of the substantia nigra modulates motor activity but is not involved importantly in regulating food and water intake”. Naunyn-Schmiedeberg’s Archives of Pharmacology. 313 (1): 51–67. doi:10.1007/BF00505805PMID 7207636.
  5. Jankovic J (April 2008). “Parkinson’s disease: clinical features and diagnosis”. Journal of Neurology, Neurosurgery, and Psychiatry. 79 (4): 368–76. doi:10.1136/jnnp.2007.131045PMID 18344392.
  6. Dawson TM, Dawson VL (October 2003). “Molecular pathways of neurodegeneration in Parkinson’s disease”. Science. 302 (5646):819-22.