The Putamen is a large subcortical nucleus that forms the lateral portion of the striatum, the major input structure of the basal ganglia. As a critical component of the motor loop, the putamen is essential for movement initiation, execution, habit formation, and reward processing. This page provides comprehensive information about its anatomical structure, physiological functions, neurochemical properties, and pivotal role in neurodegenerative diseases, particularly Parkinson's disease (PD) and Huntington's disease (HD).
| Property |
Value |
| Category |
Dorsal Striatum, Basal Ganglia |
| Location |
Lateral portion of the striatum, dorsal to the globus pallidus, lateral to the caudate nucleus |
| Cell Types |
Medium spiny neurons (D1 and D2), fast-spiking interneurons, low-threshold spiking interneurons, cholinergic interneurons |
| Primary Neurotransmitters |
GABA (output), Dopamine (modulation) |
| Key Markers |
DARPP32, D1R, D2R, PV (parvalbumin), Calbindin, Enkephalin |
| Volume (human) |
Approximately 5-6 cm³ total |
| Cell Count |
~100 million neurons in adult human |
¶ Location and Boundaries
The putamen is located in the basal ganglia, deep within the cerebral hemispheres:
- Anterior: Continuous with the head of the caudate nucleus (separated by the anterior limb of the internal capsule)
- Posterior: Borders the globus pallidus (external segment, GPe) laterally
- Superior: Adjacent to the external capsule and claustrum
- Inferior: Separated from the amygdala by the ansa lenticularis
- Lateral: Covered by the external capsule and extreme capsule
The putamen contains diverse neuronal populations:
- D1-MSNs (direct pathway): Express dopamine D1 receptors, substance P; project directly to the substantia nigra pars reticulata (SNr) and globus pallidus internus (GPi)
- D2-MSNs (indirect pathway): Express dopamine D2 receptors, enkephalin; project to the external segment of the globus pallidus (GPe)
- Account for ~90-95% of all neurons in the putamen
- Have dense dendritic spines ("spiny" appearance)
- Fast-spiking parvalbumin (PV) interneurons: Provide powerful inhibition to MSNs
- Low-threshold spiking (LTS) interneurons: Express somatostatin and neuropeptide Y
- Cholinergic interneurons (tonically active neurons, TANs): Release acetylcholine and modulate MSN activity
- Account for ~5-10% of the neuronal population
The putamen exhibits neurochemical compartmentalization:
- Striosomes: Patch-like compartments rich in μ-opioid receptors, D1 receptors, and substance P
- Matrix: Surrounding matrix compartments rich in calbindin, D2 receptors, and enkephalin
- These compartments may have different vulnerability in disease states
The putamen is a central hub for motor control:
- Movement initiation: Receives motor cortex input and initiates movement through the basal ganglia thalamocortical loops
- Movement scaling: Modulates the amplitude and force of movements
- Movement sequence execution: Controls sequential movements and procedural learning
- Motor habit formation: Critical for converting goal-directed actions into automatic habits [1]
Motor Cortex → Putamen (D1-MSNs) → GPi/SNr → Thalamus → Motor Cortex (Facilitated)
- Facilitates wanted movements
- Dopamine D1 receptor activation promotes movement
Motor Cortex → Putamen (D2-MSNs) → GPe → STN → GPi/SNr → Thalamus → Motor Cortex (Inhibited)
- Suppresses unwanted movements
- Dopamine D2 receptor activation disinhibits movement
The putamen processes reward-related information:
- Reinforcement learning: Signals reward prediction errors
- Habit formation: Converts reward-seeking behaviors into automatic habits
- Value-based decision making: Encodes the value of actions and outcomes
- Response to reward: Activates during receipt of expected and unexpected rewards
Beyond motor control, the putamen contributes to:
- Working memory: Maintains task-relevant information
- Sequence learning: Encodes sequential patterns
- Category learning: Supports categorization of stimuli
Dopamine from the substantia nigra pars compacta (SNc) critically modulates putamen function:
| Receptor Type |
Pathway |
Effect of Dopamine |
Effect in PD |
| D1 (D1-MSNs) |
Direct |
Excitatory |
↓ Movement initiation |
| D2 (D2-MSNs) |
Indirect |
Inhibitory (disinhibition) |
↑ Movement inhibition |
MSNs produce GABA as their primary neurotransmitter:
- Projection targets: GPi, SNr, GPe
- Effect: Inhibitory, shaping basal ganglia output
- Pathology: Altered GABA signaling in HD and PD
Cholinergic interneurons (TANs) play important roles:
- Modulate MSN excitability
- Involved in reward learning
- Targeted in some therapeutic approaches
The putamen is severely affected in PD:
- Dopaminergic denervation: The putamen receives the densest dopaminergic innervation from the SNc, making it highly vulnerable to degeneration
- Neuronal loss: Up to 50-70% of putaminal MSNs are lost in advanced PD
- Pathology: Lewy bodies (α-synuclein aggregates) accumulate in putaminal neurons
- Functional consequences:
- Impaired movement initiation (bradykinesia)
- Increased muscle rigidity
- Resting tremor (via thalamic disinhibition)
- Levodopa: Restores dopamine in the putamen to improve motor symptoms
- Deep brain stimulation: GPi or STN stimulation modulates putaminal output
- Dopamine agonists: Directly stimulate D1/D2 receptors in the putamen
The putamen shows early and severe degeneration in HD:
- MSN loss: Early preferential loss of D2-MSNs (indirect pathway)
- Neuropathology: Mutant huntingtin protein aggregates in striatal neurons
- Clinical manifestations:
- Chorea (involuntary movements)
- Dystonia
- Cognitive decline
- Striosome vulnerability: Early degeneration of striosome compartments
| Disease |
Putamen Involvement |
Clinical Relevance |
| Multiple System Atrophy (MSA) |
Striatal degeneration |
Severe motor impairment |
| Progressive Supranuclear Palsy |
Tau pathology in striatum |
Falls, parkinsonism |
| Corticobasal Degeneration |
Asymmetric putaminal atrophy |
Apraxia, rigidity |
| Dementia with Lewy Bodies |
Lewy body pathology |
Cognitive fluctuations |
| Source |
Neurotransmitter |
Function |
| Motor Cortex |
Glutamate |
Movement initiation |
| Premotor Cortex |
Glutamate |
Movement planning |
| Supplementary Motor Area |
Glutamate |
Sequence planning |
| Somatosensory Cortex |
Glutamate |
Sensory feedback |
| Thalamus (centromedian/parafascicular) |
Glutamate |
Modulatory input |
| Substantia Nigra pars compacta |
Dopamine |
Reward/motor modulation |
| Raphe Nuclei |
Serotonin |
Mood/motivation modulation |
| Target |
Pathway |
Effect |
| Globus Pallidus externus (GPe) |
D2-MSNs (indirect) |
Inhibition → movement suppression |
| Globus Pallidus internus (GPi) |
D1-MSNs (direct) |
Inhibition → movement facilitation |
| Substantia Nigra pars reticulata (SNr) |
D1-MSNs (direct) |
Inhibition → movement facilitation |
- MRI: Structural imaging to measure putaminal volume and atrophy
- Diffusion Tensor Imaging (DTI): Assess white matter integrity
- fMRI: Functional activation during motor and cognitive tasks
- PET: Dopamine transporter binding, glucose metabolism
- Intracellular recordings: Characterize MSN membrane properties
- Extracellular unit recordings: Single-neuron activity in vivo
- Local field potentials (LFPs): Oscillatory activity in the basal ganglia
- Immunohistochemistry: Protein localization
- In situ hybridization: Gene expression patterns
- Single-cell RNA-seq: Transcriptomic profiling
- MRI: Rule out structural lesions, assess atrophy patterns
- DaTSPECT: Dopamine transporter imaging (reduced in PD)
- FDG-PET: Metabolic patterns (reduced putaminal metabolism in PD)
- CSF biomarkers: α-synuclein, tau, amyloid
- UPDRS (Unified Parkinson's Disease Rating Scale): Motor examination
- Huntington's Disease Rating Scale: Motor and cognitive assessment
- Timed Up and Go: Functional mobility
- Dopamine precursors (Levodopa): Bypass degenerated SNc
- Dopamine agonists: Bromocriptine, pramipexole, rotigotine
- MAO-B inhibitors: Selegiline, rasagiline
- COMT inhibitors: Entacapone, tolcapone
- Deep Brain Stimulation (DBS): GPi or STN targets
- Lesioning: Pallidotomy, thalamotomy
- Cell transplantation: Dopaminergic cell replacement (experimental)
- Gene therapy: AAV-based gene delivery
- Immunotherapy: α-synuclein-targeted antibodies
- Neuroprotective agents: Disease-modifying compounds
The study of Putamen 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.
- Graybiel AM. Habits, rituals, and the evaluative brain. Annu Rev Neurosci. 2008;31:359-387.
- Obeso JA, Rodriguez-Oroz MC, Benitez-Temino B, et al. Functional organization of the basal ganglia: therapeutic implications for Parkinson's disease. Mov Disord. 2008;23(Suppl 3):S548-S559.
- Albin RL, Young AB, Penney JB. The functional anatomy of basal ganglia disorders. Trends Neurosci. 1989;12(10):366-375.
- DeLong MR, Wichmann T. Circuits and circuit disorders of the basal ganglia. Arch Neurol. 2007;64(1):20-24.
- Parent A, Hazrati LN. Functional anatomy of the basal ganglia. I. The cortico-striato-pallido-thalamo-cortical loop. Brain Res Rev. 1995;20(1):91-127.
- Kreitzer AC, Malenka RC. Striatal plasticity and basal ganglia circuit function. Nature. 2008;455(7213):643-649.
- Surmeier DJ, Song WJ, Yan Z. The origins of the dopaminergic innervation of the dorsal striatum. J Comp Neurol. 1996;364(3):540-554.