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Pars compacta

The substantia nigra pars compacta (SNpc) is a densely packed cluster of neurons located in the , forming the dorsomedial portion of the and characterized by its dark pigmentation due to high content from synthesis. This structure serves as the primary source of projections to the via the , playing a critical role in modulating motor movement, reward processing, and circuitry. Degeneration of SNpc neurons is the hallmark of , leading to depletion in the and motor symptoms such as bradykinesia, rigidity, and tremors.

Anatomy

Location and gross anatomy

The pars compacta (SNc) forms the dorsal subdivision of the , a key component of the basal ganglia's in the . It is situated in the ventral of the , positioned dorsal to the cerebral peduncles (crus cerebri) and ventral to the . Laterally, it relates to the , while medially it borders the subthalamic nucleus. This paired structure lies bilaterally, symmetric across the midline, and spans the anterior at the junction between the and the cerebral peduncles. In adult humans, the pars compacta exhibits a compact, elongated structure with a rostrocaudal extent of approximately 14 mm and a typical width of about 12 mm at its broadest point near the level. The structure tapers superiorly and inferiorly, contributing to its lens-like or tear-drop profile in sagittal views. On gross examination, the pars compacta appears as a darkly pigmented band due to the accumulation of within its neurons, earning the its name ("black substance"). This pigmentation contrasts sharply with the lighter, less pigmented pars reticulata immediately ventral to it, making the subdivision visible even in unstained sections. The dark hue is particularly prominent in and becomes more evident with age.

Microscopic anatomy

The pars compacta (SNpc) primarily consists of neurons belonging to the A9 group, which constitute the main neuronal population in this region. In humans, there are approximately 400,000 to 500,000 such neurons on each side of the . These neurons are characterized by large somata with diameters typically ranging from 20 to 50 μm and extensive dendritic arbors that contribute to their integrative properties. A distinctive feature of these neurons is the presence of granules, which are iron-rich responsible for the dark coloration of the SNpc. is synthesized through the oxidation of and its metabolites, forming a complex that binds iron and other metals. This is uniquely abundant in SNpc neurons and absent in populations of other regions, such as the . The SNpc contains few local , primarily or in nature, alongside supporting glial cells including and . In healthy tissue, there are no significant glial scars or reactive , maintaining a relatively sparse non-neuronal matrix. Histologically, dopaminergic neurons are identified through immunoreactivity for (TH), the rate-limiting enzyme in synthesis, while Nissl staining highlights their clustered arrangement in ventral tiers within the pars compacta.

Neural connections

The pars compacta (SNc) primarily sends efferent projections via the to the dorsal , including the and , where these fibers provide dense innervation essential for modulating function. Minor efferent projections from the SNc also target the ventral , , and , supporting limbic and cognitive processing. Afferent inputs to the SNc include projections from the via the direct and indirect pathways, which provide inhibitory feedback to dopaminergic neurons. Additional afferents arise from the and , while the subthalamic nucleus contributes to excitatory modulation. Excitatory glutamatergic inputs to the SNc originate from cortical regions, such as and sensorimotor areas, as well as from thalamic nuclei, facilitating sensory and cognitive integration. Dopaminergic terminals from the SNc form en passant varicosities in the , creating an lattice that apposes spines and dendritic shafts of medium spiny neurons, often in close proximity to terminals from cortical and thalamic sources. These terminals establish symmetrical synapses, enabling volume transmission of . The SNc also maintains reciprocal connections with the substantia nigra pars reticulata, allowing intra-nigral modulation that influences firing patterns through mechanisms. SNc projections exhibit pathway specificity, with denser innervation in striatal compartments compared to , preferentially influencing receptor-expressing medium spiny neurons in patches that project to the SNc. In contrast, regions, which contain a mix of - and D2-expressing neurons, receive comparatively sparser innervation, supporting differential roles in limbic versus sensorimotor processing.

Development

Embryonic origins

The pars compacta of the originates from the floor plate of the embryonic , specifically within the ventral mesencephalon, during early human gestation. Progenitor cells for neurons begin to form around gestational week 6.5 in the ventricular zone, induced by Sonic hedgehog (Shh) signaling emanating from the floor plate, which patterns the ventral midline and specifies initial dopaminergic progenitors. These progenitors subsequently migrate dorsally from the floor plate to populate the prospective pars compacta region. Critical transcription factors drive the specification and of these neurons, including Nurr1 (NR4A2), which is essential for the early of progenitors, and Pitx3, which cooperates with Nurr1 to promote terminal maturation toward the . Additionally, Engrailed 1 and 2 (En1/2) genes play key roles in the and proper development of these neurons during embryogenesis. In human embryos, the timeline of pars compacta formation progresses rapidly: by gestational week 8, tyrosine hydroxylase (TH)-positive neurons, marking dopaminergic identity, begin to extend projections forming the nigrostriatal bundle. An initial population of postmitotic neurons emerges around weeks 11-12, with TH expression becoming detectable in ventral midbrain clusters by week 13. The substantia nigra as a whole is delineated by week 16 as a compact group of intermingled neurons and fibers, and distinct clusters of dopaminergic neurons, including those destined for the pars compacta, appear by week 19 in the ventral midbrain.

Postnatal maturation

Following birth, the neurons of the pars compacta (SNc) undergo significant morphological refinement, particularly in dendritic and axonal growth. In , dendritic arborization expands rapidly after postnatal day 7 (P7), with the length of axonal branches in the dorsal peaking around P14, marking a non-linear trajectory that aligns with the transition to early functional maturity. This period corresponds roughly to early infancy in humans, where similar arborization processes contribute to the establishment of nigrostriatal projections, though human axonal and dendritic maturation extends progressively into , supporting the refinement of motor and reward circuits. Electrophysiological properties of SNc neurons also mature postnatally, shifting from bursting patterns to a stable firing rate of 3-8 Hz by approximately P14-P21 in . shape and amplitude stabilize during this timeframe, reflecting changes in expression that enhance excitability and pacemaking precision. These developments ensure reliable signaling, with the non-linear progression underscoring critical windows for synaptic integration. Neurotrophic factors play a pivotal role in this maturation, with (BDNF) being essential for the survival, differentiation, and axonal targeting of SNc neurons. BDNF supports the elimination of excess connections through regulated during early postnatal critical periods, preventing overgrowth and promoting circuit specificity. In humans, these processes manifest uniquely, with —a derived from oxidation—beginning to accumulate in SNc neurons around age 3 years, reaching substantial levels by and continuing to increase until approximately age 20. Full integration of SNc projections into circuits, including striatal innervation, matures by late childhood and extends through adolescence, coinciding with the refinement of density and reward processing.

Function

Dopaminergic signaling

In dopaminergic neurons of the substantia nigra pars compacta, dopamine synthesis begins with the conversion of the amino acid tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA) by the enzyme tyrosine hydroxylase (TH), which serves as the rate-limiting step in the pathway. L-DOPA is then rapidly decarboxylated to dopamine by aromatic L-amino acid decarboxylase (also known as DOPA decarboxylase). This biosynthetic process is tightly regulated, including through tetrodotoxin-sensitive mechanisms that link neuronal activity to synthesis rates, ensuring dopamine production aligns with firing patterns. Following synthesis, dopamine is sequestered into synaptic vesicles by the (VMAT2), which actively transports it from the into vesicles to prevent cytosolic accumulation and . Release occurs via two primary modes: tonic release, characterized by low baseline extracellular concentrations of 1-5 nM maintained by irregular single-spike firing at frequencies around 0.2-3 Hz, and phasic release, involving burst firing that can elevate dopamine levels up to 100-fold in response to salient stimuli. Both modes depend on calcium-dependent at terminals, where voltage-gated calcium channels trigger vesicle fusion. Extracellular dopamine is primarily cleared through reuptake by the (DAT) on presynaptic membranes, recycling it for vesicular repackaging or metabolism. Metabolically, dopamine undergoes oxidative deamination by (MAO) to form 3,4-dihydroxyphenylacetic acid (DOPAC), which is further processed extracellularly by (COMT) to yield homovanillic acid (HVA), the major end product excreted in urine. Neuromodulation is achieved via D2 autoreceptors on somatodendritic and axonal regions, which provide inhibition by hyperpolarizing the through G-protein-coupled potassium channels, thereby dampening , firing, and release to maintain .

Role in basal ganglia circuitry

The substantia nigra pars compacta (SNc) plays a central role in the circuitry by releasing that modulates the direct and indirect pathways originating from the . In the direct pathway, binds to receptors on medium spiny neurons (MSNs), depolarizing these cells and increasing their excitability, which facilitates the transmission of excitatory signals to the internal (GPi) and substantia nigra pars reticulata (SNr). This activation ultimately leads to of thalamocortical projections, promoting movement initiation and vigor. Conversely, in the indirect pathway, dopamine acts on D2 receptors expressed by MSNs, which are coupled to inhibitory G-proteins; this binding hyperpolarizes the neurons, reducing their activity and thereby diminishing inhibitory output to the external (GPe). The resulting decrease in GPe inhibition of the subthalamic nucleus (STN) and subsequent effects on GPi/SNr help suppress competing motor programs. The balanced modulation of these opposing pathways by SNc prevents hypokinetic states and ensures coordinated motor selection. Beyond , SNc dopamine neurons contribute to reward processing through phasic bursts that encode reward errors (RPEs) in the loop. These bursts increase firing for unexpected rewards, signaling positive RPE to strengthen striatal synapses via , while pauses or decreases in firing occur for omitted expected rewards, indicating negative RPE and promoting synaptic depression for learning adjustments. This RPE signaling, primarily targeting the ventral striatum, shapes associative learning and formation by updating value representations in the over time.00467-8) Tonic dopamine release from SNc maintains baseline excitability in striatal circuits, supporting sustained motor readiness and preventing excessive inhibition that could lead to bradykinesia or tremors. Disruptions in this modulation, such as reduced levels, impair the overall balance of pathway activity, resulting in altered thalamic gating and motor deficits. Phasic signals build upon this tonic foundation to fine-tune behavioral responses in .

Additional physiological roles

The substantia nigra pars compacta (SNc) contributes to various cognitive functions beyond , including , , and spatial . Dopaminergic projections from the SNc modulate and processes in prefrontal and striatal circuits, facilitating the maintenance and manipulation of information during tasks requiring sustained focus. Similarly, SNc neurons are integral to attentional mechanisms, particularly spatial attention, through interactions with networks that enhance orienting responses to salient environmental cues. In spatial , SNc dopaminergic activity supports place learning strategies and route optimization, integrating sensory inputs with goal-directed in striatal pathways. Additionally, the SNc forms part of an independent system akin to hippocampal functions, specialized for temporal processing, where it encodes intervals and sequences essential for timing-based . In reward and learning, SNc dopaminergic neurons signal habituation to repeated neutral stimuli while exhibiting sustained phasic bursts for novel or rewarding events, encoding reward prediction errors that drive across cortical and targets. This differential activity promotes adaptive behavior by reinforcing associations between actions and outcomes, with habituation reducing responses to predictable, non-rewarding inputs to conserve neural resources.00475-2) The SNc also participates in sleep-wake regulation through dopaminergic projections to the and , influencing states and promoting via modulation of D1 and D2 receptors in these regions. These projections help maintain vigilance and transition between stages, particularly enhancing rapid eye movement (REM) sleep onset and stability. Furthermore, SNc neurons modulate sensory processing, particularly visual and auditory responses, via collateral projections to the , which sharpen orienting reflexes and filter irrelevant stimuli for efficient perceptual integration.

Clinical significance

Parkinson's disease

is characterized by the selective degeneration of neurons in the pars compacta, with up to 70% loss occurring by the time motor symptoms manifest. This neuronal death is accompanied by the formation of intraneuronal inclusions known as Lewy bodies, which consist primarily of aggregated protein. These pathological changes disrupt production and release, leading to the core motor impairments of the disease, including resting tremor, rigidity, and bradykinesia. Motor symptoms typically emerge only after substantial dopamine depletion in the striatum, estimated at 70-80%, corresponding to a 50-60% loss of dopaminergic neurons in the SNpc, due to compensatory mechanisms that mask earlier deficits. In contrast, non-motor symptoms such as and can appear years prior to motor onset, reflecting initial involvement of other neural systems. The underlying involves mitochondrial dysfunction, which impairs energy production and promotes ; oxidative stress exacerbated by neuromelanin-bound iron and dopamine oxidation; and protein misfolding leading to aggregation. According to , the disease progresses caudorostrally, beginning in the (stages 1-2), advancing to the (stages 3-4) where motor symptoms arise, and eventually affecting cortical regions (stages 5-6). Diagnosis of relies on clinical assessment, but imaging biomarkers like DaTSCAN, which visualizes loss in the , aid in confirming presynaptic deficits. Postmortem confirmation involves histological examination of the , where staining reveals the extent of neuron loss and presence.

Other associated disorders

The pars compacta (SNpc) has been implicated in through the hyper hypothesis, which posits elevated activity originating from increased synthesis in this region, contributing to psychotic symptoms. Studies using have shown heightened striatal synthesis capacity linked to SNpc dysregulation in affected individuals. medications, which primarily act as antagonists at D2 receptors expressed on SNpc neurons, help normalize this hyperdopaminergic state by reducing excessive signaling. In addiction and reward-related disorders, dysfunction in the SNpc manifests as altered phasic signaling, where drugs of hijack the rapid, burst-like release of from these neurons to reinforce compulsive behaviors. This phasic dysregulation in the SNpc and connected pathways enhances of drug cues, driving the transition from voluntary use to . Animal models employing the toxin demonstrate acute neuron loss in the SNpc, replicating parkinsonian symptoms and providing insights into how sudden depletion mimics aspects of reward circuit disruption in substance use disorders. Neurodegenerative conditions beyond Parkinson's show secondary involvement of the SNpc, often to a lesser extent than primary striatal . In , dopamine imbalance arises from indirect effects on SNpc projections, with milder neuronal loss compared to the , contributing to early hyperkinetic symptoms. features tau inclusions in SNpc neurons alongside significant degeneration, exacerbating motor and oculomotor deficits. Ongoing research targets SNpc dysfunction across these disorders through innovative approaches. Stem cell therapies aim to replace lost dopaminergic neurons in the SNpc using embryonic or induced pluripotent -derived progenitors, showing promise in preclinical and early clinical trials for restoring nigrostriatal pathways. Recent 2025 developments include nanoparticle-based wireless systems that eliminate α-synuclein aggregates and restore SNpc neurons, as well as reprogramming to generate transplantable neurons. Optogenetic studies in circuits, including SNpc modulation, have demonstrated restoration of motor function in animal models by precisely activating or inhibiting projections. Genetic investigations highlight mutations in as risk factors extending beyond Parkinson's to influence tauopathies and other synucleinopathies via impaired activity affecting SNpc neuronal health.

References

  1. [1]
    Neuroanatomy, Substantia Nigra - StatPearls - NCBI Bookshelf - NIH
    The substantia nigra (SN) is a midbrain dopaminergic nucleus, which has a critical role in modulating motor movement and reward functions as part of the basal ...Introduction · Structure and Function · Embryology · Physiologic Variants
  2. [2]
    Substantia nigra: Anatomy, structure and function - Kenhub
    Due to these connections, the pars compacta is considered a critical part of the basal ganglia pathways and thus it has a prominent function in motor control.
  3. [3]
    Substantia Nigra Pars Compacta - an overview | ScienceDirect Topics
    The substantia nigra pars compacta (SNc) is defined as a brain region involved in dopamine projection to the striatum, playing a central role in the physiology ...
  4. [4]
    Basal Ganglia (Section 3, Chapter 4) Neuroscience Online
    The substantia nigra is located between the red nucleus and the crus cerebri (cerebral peduncle) on the ventral part of the midbrain. The pars compacta is the ...Missing: position | Show results with:position
  5. [5]
    Substantia Nigra Pars Compacta - an overview | ScienceDirect Topics
    It is involved in the regulation of important brain functions including motor, reward-related and cognitive behaviors. Abnormal functioning or degeneration of ...The Basal Ganglia · Midbrain Dopamine Neurons... · Connections<|control11|><|separator|>
  6. [6]
    Substantia nigra | Radiology Reference Article - Radiopaedia.org
    May 10, 2022 · Gross anatomy. They are situated in the anterior midbrain and mark ... Related articles: Anatomy: Brain. Anatomy: Brain · brain · grey matter ...
  7. [7]
    9.4 T MR microscopy of the substantia nigra with pathological ...
    The SN is most broad and deep at the level of the RN (mean width 11.72 mm; mean depth 2.99 mm), tapering at the superior extremity and resembling a tear in the ...
  8. [8]
    Anatomical & Functional Organization of Human Substantia Nigra
    Despite variations in brain shapes and gross anatomy, the approach identifies the correct location for human substantia nigra on average. All individual ...
  9. [9]
    Substantia Nigra Pars Compacta - an overview | ScienceDirect Topics
    Substantia Nigra. In the normal brain, the substantia nigra contains neuromelanin which gives it a dark pigmented appearance on gross examination.
  10. [10]
    Evidence That Substantia Nigra Pars Compacta Dopaminergic ...
    Mar 4, 2022 · There are 400–500 thousand dopaminergic cells within each side of the human substantia nigra pars compacta (SNpc) making them a minuscule ...
  11. [11]
    Balance between the proximal dendritic compartment and the soma ...
    In the rat substantia nigra pars compacta (SNc) DA neurons, we demonstrate that the balance between the proximal dendritic compartment and the soma determines ...
  12. [12]
    Dendritic Architecture Predicts in vivo Firing Pattern in Mouse ...
    Nov 18, 2021 · Dopaminergic neurons of the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) are involved in important brain functions ...
  13. [13]
    Neuromelanin, one of the most overlooked molecules in modern ...
    Neuromelanin (NM) in the pre-synaptic terminal of dopamine neurons is emerging as a primary player in the etiology of neurodegenerative disorders including PD.
  14. [14]
    Neuromelanin and selective neuronal vulnerability to Parkinson's ...
    Instead, dopamine metabolites likely contribute to neuromelanin pigmentation because iron can catalyze oxidation of dopamine to quinones [77]. Iron accumulation ...
  15. [15]
    Induction of Ferroptotic Cell Death by Neuromelanin Pigments in ...
    Mar 27, 2025 · Our findings reveal a distinct role of iron-rich and iron-free neuromelanin in modulating ferroptotic pathways.
  16. [16]
    Ih Channels Contribute to the Different Functional Properties of ...
    Feb 15, 2002 · Dopaminergic (DA) midbrain neurons in the substantia nigra (SN) and ... (20–50 μg/ml). For cell filling, at the end of perforated-patch ...
  17. [17]
    Three-dimensional reconstruction of substantia nigra pars compacta ...
    To clarify the peculiarities of the morphochemical organization of the substantia nigra (SN) of a human brain and to create a threedimensional model of pars ...Missing: size | Show results with:size
  18. [18]
    The substantia nigra of the human brain - Oxford Academic
    We defined the substantia nigra as the midbrain region ventral to the medial lemniscus and the substantia nigra pars compacta as the region containing calbindin ...
  19. [19]
    https://doi.org/10.3390/app15147902
  20. [20]
    https://doi.org/10.1523/JNEUROSCI.2780-08.2008
  21. [21]
    https://doi.org/10.3389/fnsys.2011.00025
  22. [22]
    https://doi.org/10.1016/j.neuron.2016.07.046
  23. [23]
    Spatiotemporally separable Shh domains in the midbrain define ...
    We have recently shown that in the embryonic CNS, mDA originate from the midbrain floor plate, a ventral midline structure that is operationally defined by the ...
  24. [24]
    Midbrain Dopaminergic Neuron Development at the Single Cell Level
    All mDA neurons appear to arise from VM floor plate progenitors that express Shh and respond to high levels of Shh signaling (as assessed by Gli1 expression) ...
  25. [25]
    Nurr1 Is Required for Maintenance of Maturing and Adult Midbrain ...
    Dec 16, 2009 · Nurr1, one such transcription factor, is essential for early differentiation of midbrain dopamine (mDA) neurons but continues to be expressed into adulthood.Conditional Nurr1... · Selective Nurr1 Ablation In... · Loss Of Mda Neuron...
  26. [26]
    Cooperative transcription activation by Nurr1 and Pitx3 induces ...
    Here we show that Nurr1 and Pitx3 synergistically promote terminal maturation to the midbrain DA neuron phenotype in murine and human ES cell cultures.
  27. [27]
    Transcriptional Control of Dopamine Neuron Development - 2003
    Jan 24, 2006 · ... transcription factors important for postmitotic DA cell development have been characterized. These include Nurr1, Lmx1b, Pitx3, and En1/En2.
  28. [28]
    Developing substantia nigra in human: a qualitative study - PubMed
    By 13 weeks cells could be identified as neurons and glia. Neurons matured gradually and achieved adult characteristics by 20-22 weeks. Neurons in the ...Missing: expression timeline
  29. [29]
    Molecular anatomy of the development of the human substantia nigra
    At week 16, the substantia nigra was clearly delineated as a compact group of intermingled neurons and fibers. From week 19, groups of DA neurons were ...
  30. [30]
    Postnatal Development of Dendritic Morphology and Action ...
    Apr 7, 2025 · Substantia nigra pars compacta (SNc) dopaminergic (DA) neurons are characterized by specific morphological and electrophysiological ...
  31. [31]
    Parallel Maturation of Goal-Directed Behavior and Dopaminergic ...
    Nov 14, 2012 · We investigate whether a differential developmental time course of dopamine (DA) pathways during late adolescence could explain the emergence of particular ...
  32. [32]
    Non-linear developmental trajectory of electrical phenotype in rat ...
    Oct 20, 2014 · This study provides the first comprehensive analysis of postnatal development of the intrinsic properties of SNc dopaminergic neurons and ...
  33. [33]
    Brain-Derived Neurotrophic Factor Is Required for the Establishment ...
    Jun 29, 2005 · Brain-Derived Neurotrophic Factor Is Required for the Establishment of the Proper Number of Dopaminergic Neurons in the Substantia Nigra Pars ...
  34. [34]
    Brain-Derived Neurotrophic Factor Regulates Early Postnatal ...
    Brain–derived neurotrophic factor (BDNF) was the first purified molecule identified to directly support the development of mesencephalic dopamine neurons.
  35. [35]
    Evidence for specific phases in the development of ... - PubMed
    Neuromelanin is not present at birth, starts around 3 years, increases until 20, and darkens but doesn't grow much after 20.
  36. [36]
    Maturation of the human striatal dopamine system revealed by PET ...
    Feb 12, 2020 · Our results provide new evidence for maturational specialization of the striatal DA system through adolescence.<|control11|><|separator|>
  37. [37]
    Mechanisms and regulation of dopamine release - PMC
    The midbrain dopamine system is composed of two major pathways with distinct functions [1–3], The nigrostriatal pathway originates from dopamine neurons in the ...
  38. [38]
    Regulation of the Dopamine and Vesicular Monoamine Transporters
    After synthesis, VMAT2 transports DA from the cytoplasmic space into synaptic vesicles within presynaptic terminals. VMAT2 activity largely dictates quantal ...
  39. [39]
    Controls of Tonic and Phasic Dopamine Transmission in the Dorsal ...
    Those tonic and phasic signals arise from midbrain DA neurons of the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) that innervate the ...
  40. [40]
    Differential Calcium Dependence of Axonal Versus Somatodendritic ...
    Midbrain dopamine (DA) neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) exhibit somatodendritic release of DA.
  41. [41]
    Complexity of dopamine metabolism
    May 17, 2013 · The main DA degradation products are DOPAC and HVA. In cytoplasmic vesicles NM is built of DA oxidation products and other components and can ...
  42. [42]
    The Role of D2-Autoreceptors in Regulating Dopamine Neuron ...
    Dopamine D2-autoreceptors play a key role in regulating the activity of dopamine neurons and control the synthesis, release and uptake of dopamine.
  43. [43]
    Modulation of striatal projection systems by dopamine - PMC
    Activation of D1 receptors in direct pathway SPNs increases their excitability and promotes long-term potentiation of excitatory synapses. In contrast, ...
  44. [44]
    Basal ganglia for beginners: the basic concepts you need to know ...
    Aug 3, 2023 · The key to understand what determines the activity of both direct and indirect pathways are in the nigrostriatal dopaminergic pathway. Dopamine ...
  45. [45]
    The dopamine reward prediction error hypothesis - PubMed Central
    The phasic activity of midbrain dopamine neurons encodes a reward prediction error used to guide learning throughout the frontal cortex and the basal ganglia.
  46. [46]
    A neurocomputational model of tonic and phasic dopamine in action ...
    Tonic dopamine levels modulate currents that control the excitability of MSNs. ... The basal ganglia: focused selection and inhibition of competing motor programs ...
  47. [47]
    Basal ganglia circuit loops, dopamine and motivation - PMC - NIH
    Afferent modulation of dopamine neuron firing differentially regulates tonic and phasic dopamine transmission. Nature Neuroscience. 2003;6:968–73. doi ...
  48. [48]
    Evidence for direct dopaminergic connections between substantia ...
    Jan 8, 2025 · The substantia nigra pars compacta (SNc), one of the main dopaminergic nuclei of the brain, exerts a regulatory function on the basal ganglia ...Missing: crescent- | Show results with:crescent-
  49. [49]
    Control from below: the role of a midbrain network in spatial attention
    Emerging evidence shows that a midbrain network also plays a critical role in controlling spatial attention.
  50. [50]
    The Cognitive Architecture of Spatial Navigation: Hippocampal and ...
    Oct 7, 2015 · Here we examine the cognitive architecture of spatial navigation, with a focus on hippocampal and striatal systems and their interaction.
  51. [51]
    The Substantia Nigra Pars Compacta and Temporal Processing
    Nov 22, 2006 · ... size, 2.4 × 2.1 × 2.1 mm), with a resolution of 6 mm at full ... (1991) The human brain: surface, blood supply, and three-dimensional ...
  52. [52]
    Evidence for the substantia nigra pars compacta as an essential ...
    Evidence for the substantia nigra pars compacta as an essential component of a memory system independent of the hippocampal memory system. Author links open ...
  53. [53]
    Understanding dopamine and reinforcement learning - PNAS
    The phasic activity of midbrain dopamine neurons encodes a reward prediction error used to guide learning throughout the frontal cortex and the basal ganglia.
  54. [54]
    Dopaminergic Control of Sleep–Wake States
    Oct 11, 2006 · Sleep disturbances are known to occur in both schizophrenia and Parkinson's disease, suggesting that dopamine plays a role in regulating the sleep–wake cycle.
  55. [55]
    The Role of the Substantia Nigra Pars Compacta in Regulating ...
    The main findings herein are that the dopaminergic neurons located within the SNpc played an important role in regulating sleep patterns in rats, and that ...
  56. [56]
    Superior Colliculus Controls the Activity of the Substantia Nigra Pars ...
    Apr 2, 2025 · Our research describes an SC-originating neuronal circuit that directly enhances the activity of ipsilateral DA neurons while simultaneously diminishing the ...
  57. [57]
    Neuronal Vulnerability in Parkinson Disease and Putative ...
    Oct 1, 2020 · ... neurons especially vulnerable in PD. An approximate 70% loss of dopamine (DA) neurons in the SNc defines PD, and contributes to the majority ...
  58. [58]
    Modeling Parkinson's Disease With the Alpha-Synuclein Protein
    The neuropathological hallmark of PD is the abnormal accumulation and aggregation of alpha synuclein protein (α-Syn) in form of Lewy bodies and Lewy neurites ( ...Parkinson's Disease · Propagation of Alpha... · Animal Models of PD Based...
  59. [59]
    Role of dopamine in the pathophysiology of Parkinson's disease
    Sep 18, 2023 · A pathological feature of Parkinson's disease (PD) is the progressive loss of dopaminergic neurons and decreased dopamine (DA) content in the substantia nigra ...
  60. [60]
    Relationship between the Appearance of Symptoms and the Level ...
    Sep 1, 2001 · Symptom appearance was thought to require a 70–80% loss of striatal terminals, a 50–60% loss of dopaminergic neurons, and a 70–90% DA deficiency ...
  61. [61]
    Non-Movement Symptoms | Parkinson's Foundation
    Some symptoms, such as loss of smell, constipation, depression and REM sleep behavior disorder (RBD) can occur years before the diagnosis of PD. Recognizing ...Constipation & Nausea · Cognitive Changes · Hallucinations/Delusions · Anxiety
  62. [62]
    Mitochondrial dysfunction and oxidative stress in Parkinson's disease
    Altogether, these findings suggest that DJ-1 may prevent protein misfolding and aggregation under oxidative stress conditions. 6.5 LRRK2. LRRK2 (Leucine-rich ...Missing: neuromelanin | Show results with:neuromelanin
  63. [63]
    Staging of brain pathology related to sporadic Parkinson's disease
    This study traces the course of the pathology in incidental and symptomatic Parkinson cases proposing a staging procedure based upon the readily recognizable ...
  64. [64]
    Dopamine Transporter Imaging in Parkinson Disease - PMC - NIH
    Dopamine transporter (DAT) imaging is widely performed for the differential diagnosis of PD and other degenerative parkinsonism from essential tremor, vascular ...
  65. [65]
    Full article: Postmortem studies in Parkinson's disease
    Apr 1, 2022 · The substantia nigra pars compacta (SNpc) can be identified by tyrosine hydroxylase (TH) immunostaining reflecting the presence of ...
  66. [66]
    The substantia nigra in the pathology of schizophrenia: A review on ...
    Highlights. Dopamine synthesis in the substantia nigra appears to be increased in schizophrenia. There is evidence for increased glutamatergic functioning and ...
  67. [67]
    Striatal dopamine synthesis capacity and neuromelanin in the ... - NIH
    Striatal dopamine synthesis capacity and neuromelanin in the substantia nigra: A multimodal imaging study in schizophrenia and healthy controls
  68. [68]
    New Concepts in Dopamine D2 Receptor Biased Signaling and ...
    The dopamine D2 receptor (D2R) is a G protein–coupled receptor that is a common target for antipsychotic drugs. Antagonism of D2R signaling in the striatum is ...
  69. [69]
    Phasic dopamine release in appetitive behaviors and drug abuse
    Recent studies suggest that abused drugs similarly enhance phasic dopamine release events that occur on a subsecond time scale.Missing: pars compacta
  70. [70]
    Dopamine Circuit Mechanisms of Addiction-Like Behaviors - Frontiers
    In rats, phasic DA signaling in the NAc encodes motivational conflict: cues signaling threats evoke greater DA release compared to neutral cues, and this signal ...
  71. [71]
    MPTP Mouse Models of Parkinson's Disease: An Update - PMC
    Depending on the protocol used, MPTP yields large variations in nigral cell loss, striatal dopamine loss and behavioral deficits. Motor deficits do not fully ...
  72. [72]
    Dopamine imbalance in Huntington's disease: a mechanism for the ...
    Jul 3, 2013 · GABAergic striosomal neurons innervate DA neurons in the substantia nigra pars compacta and reticulata, essentially forming a third striatal ...Striatal Organization · DA Alterations in Huntington's... · DA in Animal Models of HD
  73. [73]
    Progressive Supranuclear Palsy: Pathology and Genetics - PMC
    The substantia nigra shows loss of pigment corresponding to nigrostriatal dopaminergic degeneration. Microscopic findings include neuronal loss, gliosis and ...
  74. [74]
    Phase 1/2a clinical trial of hESC-derived dopamine progenitors in ...
    Oct 13, 2025 · Parkinson's disease (PD) has long been considered an appropriate candidate for cell replacement therapy. We generated high-purity ...
  75. [75]
    Regulation of parkinsonian motor behaviors by optogenetic control ...
    Our findings establish a critical role for basal ganglia circuitry in the bidirectional regulation of motor behavior.
  76. [76]
    Function and dysfunction of leucine-rich repeat kinase 2 (LRRK2)
    LRRK2 mutations are rarely found in Alzheimer's disease (AD), but LRRK2 might play a part in tauopathies. The association of LRRK2 with the pathogenesis of ...Missing: disorders | Show results with:disorders