Striatum is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
The striatum is the largest nucleus of the basal-ganglia and serves as the primary input structure for this subcortical motor circuit. Composed of two main divisions—the caudate nucleus and the putamen—separated by the internal capsule, the striatum integrates excitatory glutamatergic inputs from the cerebral cortex and thalamus with modulatory dopaminergic signals from the substantia-nigra pars compacta . The striatum plays essential roles in motor control, action selection, reward processing, and habit formation. It is among the most severely affected brain regions in huntington-pathway and is critically involved in parkinsons through loss of dopaminergic input . [1] [1:1]
The striatum (from Latin striatus, meaning "grooved" or "striped") derives its name from the striped appearance caused by alternating bundles of gray and white matter. It is the primary gateway for cortical information entering the basal ganglia and is essential for translating cognitive and motivational signals into appropriate motor actions . [2]
The striatum is divided into functional territories: [3]
Approximately 90–95% of striatal neurons are medium spiny neurons (MSNs), also called spiny projection neurons (SPNs), which are GABAergic inhibitory neurons that constitute the sole output of the striatum . The selective vulnerability of these neurons underlies the devastating motor and cognitive symptoms of several neurodegenerative diseases. [4]
The striatum is a large, curved structure situated deep within the cerebral hemispheres: [5]
The striatum has a complex compartmental organization consisting of two interdigitating compartments: [6]
Recent research from MIT (2023) demonstrated that these compartments are differentially affected in huntington-pathway, with striosome degeneration potentially accounting for mood and motivational disturbances, while matrix degeneration produces motor impairments . [7]
Medium Spiny neurons (MSNs): Constitute approximately 90–95% of all striatal neurons. These GABAergic projection neurons are characterized by their medium-sized soma (12–20 μm) and densely spiny dendrites. MSNs exist in two major subtypes :
Interneurons: Although comprising only 5–10% of striatal neurons, interneurons exert powerful control over MSN activity:
The direct pathway promotes movement and facilitates desired motor programs :
dopamine from the substantia-nigra pars compacta activates D1 receptors on direct pathway MSNs, enhancing their activity and promoting movement.
The indirect pathway suppresses competing or unwanted movements:
Dopamine inhibits D2-MSNs via D2 receptors, reducing indirect pathway activity and thereby reducing movement suppression. Loss of dopaminergic input in Parkinson's disease leads to overactivation of the indirect pathway, producing akinesia and rigidity.
The hyperdirect pathway provides the fastest route for cortical control of basal ganglia output:
huntington-pathway is characterized by profound and selective degeneration of striatal MSNs, making the striatum the most affected brain region :
Vonsattel grading classifies striatal pathology in HD from Grade 0 (no visible atrophy, 30–40% neuronal loss) to Grade 4 (severe atrophy with >95% neuronal loss), with a dorsomedial-to-ventrolateral gradient of degeneration .
In parkinsons, the striatum itself does not primarily degenerate, but it loses its critical dopaminergic input due to substantia-nigra pars compacta neuronal death :
In MSA-P (parkinsonian subtype), the striatonigral system degenerates with prominent putaminal pathology:
corticobasal-degeneration involves asymmetric cortical and basal ganglia tau] pathology:
The striatum is a major site of dopamine neurotransmission, and its neurotransmitter dynamics are central to understanding basal ganglia function and disease :
| Neurotransmitter | Source | Receptor(s) | Function |
|---|---|---|---|
| dopamine | substantia-nigra pars compacta | D1, D2, D3, D4, D5 | Modulates direct/indirect pathway balance |
| glutamate | cortex, thalamus | AMPA, nmda-receptor receptor], mGluR | Excitatory drive to MSNs |
| gaba | MSN collaterals, interneurons | GABA-A, GABA-B | Local inhibition, MSN output |
| acetylcholine | Cholinergic interneurons | nAChR, mAChR | Reward signaling, plasticity |
| serotonin | Raphe nuclei | 5-HT1B, 5-HT2C, 5-HT6 | Modulates dopamine release |
| Endocannabinoids | MSNs (retrograde) | CB1 | Retrograde synaptic modulation |
The striatum exhibits robust forms of synaptic plasticity that underlie motor learning and habit formation:
Several imaging modalities assess striatal structure and function:
deep-brain-stimulation targets structures closely connected to the striatum:
gene-therapy: AAV-mediated delivery of glutamic acid decarboxylase (GAD) to the subthalamic nucleus; AADC gene therapy directly to the putamen
Cell replacement: stem-cell-therapy to replace lost dopaminergic innervation of the striatum
huntingtin-lowering therapies: antisense-oligonucleotide-therapy and siRNA targeting mutant huntingtin expression in the striatum
[Medium Spiny [Neurons (MSNs)/cell-types/medium-spiny-neurons
The study of Striatum has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
This section links to atlas resources relevant to this brain region.
Sidell KR, Amamath V, Montine TJ, Dopamine thioethers in neurodegeneration (2001). 2001. ↩︎ ↩︎
Gil JM, Rego AC, Mechanisms of neurodegeneration in Huntington's Disease (2008). 2008. ↩︎
Gibb WR, Functional neuropathology in Parkinson's Disease (1997). 1997. ↩︎
Whetsell WO, The mammalian striatum and neurotoxic injury (2002). 2002. ↩︎
Furukawa K et al. Motor Progression and Nigrostriatal Neurodegeneration in Parkinson Disease (2022). 2022. ↩︎
Ahlers-Dannen KE, Spicer MM, Fisher RA, RGS Proteins as Critical Regulators of Motor Function and Their Implications in Parkinson's Disease (2020). 2020. ↩︎
Kernie SG, Parent JM, Forebrain neurogenesis after focal Ischemic and traumatic brain injury (2010). 2010. ↩︎