Substantia Nigra

Anatomy

• On both sides of the midbrain floor, dorsal to the cerebral peduncle and lateral to the VTA; dark because its neurons contain neuromelanin.
• Two parts: the dorsal pars compacta (SNc; dopaminergic neurons) and the ventral pars reticulata (SNr; GABAergic output neurons).
• The SNc projects to the dorsal striatum (nigrostriatal pathway); the SNr to the thalamus (VA/VL and mediodorsal), superior colliculus and PPN.
• Blood supply: branches of the posterior cerebral artery.

Substructures

2 substructures; each has its own page.

• Substantia Nigra Pars Compacta SNcSource of the nigrostriatal dopamine pathway: supports movement and habit learning by feeding the dorsal striatum.
• Substantia Nigra Pars Reticulata SNrOne of the two output nuclei of the basal ganglia, together with the GPi: GABAergic neurons that brake the thalamus and superior colliculus.

Functions

• SNc: supplies dopamine to the dorsal striatum, supporting initiation and speed of movement and motor learning.
• Habit and skill learning: the dopamine signal in the dorsal striatum helps actions become automatic.
• SNr: together with the GPi, the output nucleus of the basal ganglia; tonically brakes the thalamus and superior colliculus, and the brake is lifted for the wanted movement.
• Eye movements: the SNr → superior colliculus pathway gates voluntary saccades.

Connections and chemistry

• SNc → dorsal striatum (nigrostriatal dopamine pathway)
• Striatum → SNr (direct pathway, GABA)
• SNr → thalamus VA/VL and mediodorsal, superior colliculus, PPN
• Subthalamic nucleus → SNr (glutamate)
• Dopamine (D1, D2 receptors), GABA

Development

Developmental course through childhood and adolescence.

• Dopaminergic neurons form in the floor of the midbrain in embryonic life; nigrostriatal connections are established before birth.
• Neuromelanin pigment accumulates with age; in children the substantia nigra does not look as dark as in adults.
• In human postmortem studies, striatal dopamine receptor density peaks in childhood and then declines.

Clinical

• Extrapyramidal side effects of antipsychotics (acute dystonia, akathisia, parkinsonism): D2 blockade in the nigrostriatal pathway; children and adolescents have a higher risk of acute dystonia.
• Tourette syndrome and tic disorders: the dopaminergic hypersensitivity hypothesis; D2 antagonists and partial agonists (aripiprazole) reduce tics.
• ADHD: stimulants raise striatal dopamine; increased SN echogenicity on transcranial ultrasound has been reported in children with ADHD (Romanos et al., 2010).
• Dopa-responsive dystonia (Segawa disease): dystonia and gait disturbance in childhood that worsen during the day; marked response to low-dose levodopa.
• Neuroleptic malignant syndrome: a life-threatening picture linked to dopamine blockade (rigidity, hyperthermia, autonomic instability).

Treatment

This region from the perspective of medication, psychotherapy and neuromodulation. Letter badges are evidence levels.

• Antipsychotic-induced acute dystonia: an anticholinergic (biperiden) or diphenhydramine; the risk is higher in adolescents and young men. For parkinsonism, dose reduction or an anticholinergic; for akathisia, propranolol. A
• Neuroleptic malignant syndrome: an emergency; stop the antipsychotic at once and give intensive supportive care (fluids, cooling). Dantrolene or bromocriptine are used in severe cases; the evidence for these drugs comes from case series. B
• Dopa-responsive dystonia (Segawa): dramatic and lasting response to low-dose levodopa; a levodopa trial is recommended in unexplained childhood dystonia. A

Assessment

Neuropsychological tasks and measures that probe this region's function.

• Neurological examination: bradykinesia, rigidity, tremor, posture (extrapyramidal signs)
• Movement disorder scales: Simpson-Angus (drug-induced parkinsonism), AIMS
• Dopamine transporter imaging (DaT-SPECT)
• Neuromelanin-sensitive MRI: the SN signal relates to striatal dopamine release capacity; in schizophrenia and in people at clinical high risk for psychosis, higher signal relates to symptom severity (Cassidy et al., 2019). A dopamine marker that needs no radiation or invasive procedure; still at the research stage. C

Lesions and damage

Clinical findings expected with damage or dysfunction.

• Loss of SNc neurons: Parkinson’s disease (bradykinesia, rigidity, resting tremor); symptoms appear once most neurons are lost.
• MPTP toxicity: selective SNc damage and parkinsonism.

In the model

How this structure is defined in the 3D model, and the data source.

Union of the CIT168 SNc and SNr probability maps (each side separately); the surface volume was matched to the CIT168 hard-label volume. CIT168 is registered to the MNI 2009c asymmetric template; its overlap with CerebrA labels on the symmetric template is high (putamen 0.89–0.90, pallidum 0.82–0.83).

References

Full citations for the card; links go to the paper (DOI) or a PubMed search.

1. Cassidy CM et al. Neuromelanin-sensitive MRI as a noninvasive proxy measure of dopamine function in the human brain. PNAS 2019;116(11):5108–5117. Search PubMed
2. Romanos M et al. Transcranial sonography of the substantia nigra in children with ADHD. J Psychiatry Neurosci 2010;35(1):55–58 (kartta vardı; 22'ye karşı 22 çocuk, öncü bulgu). Search PubMed