Striatal Cholinergic Interneurons

Striatal Cholinergic Interneurons

<table class="infobox infobox-celltype">
<tr>
<th class="infobox-header" colspan="2">Striatal Cholinergic Interneurons</th>
</tr>
<tr>
<td class="label">Allen Atlas ID</td>
<td>CS202210140_3535</td>
</tr>
<tr>
<td class="label">Lineage</td>
<td>Neuron > Cholinergic > Striatal interneuron</td>
</tr>
<tr>
<td class="label">Markers</td>
<td>CHAT, SLC18A3, SLC5A7, PDE10A, VIAAT (SLC32A1)</td>
</tr>
<tr>
<td class="label">Brain Regions</td>
<td>Caudate nucleus, Putamen, Nucleus accumbens</td>
</tr>
<tr>
<td class="label">Disease Vulnerability</td>
<td>[Parkinson's Disease](/diseases/parkinsons-disease), [Huntington's Disease](/diseases/huntingtons), Dystonia</td>
</tr>
</table>

Striatal Cholinergic Interneurons

Introduction

Striatal Cholinergic Interneurons

<table class="infobox infobox-celltype">
<tr>
<th class="infobox-header" colspan="2">Striatal Cholinergic Interneurons</th>
</tr>
<tr>
<td class="label">Allen Atlas ID</td>
<td>CS202210140_3535</td>
</tr>
<tr>
<td class="label">Lineage</td>
<td>Neuron > Cholinergic > Striatal interneuron</td>
</tr>
<tr>
<td class="label">Markers</td>
<td>CHAT, SLC18A3, SLC5A7, PDE10A, VIAAT (SLC32A1)</td>
</tr>
<tr>
<td class="label">Brain Regions</td>
<td>Caudate nucleus, Putamen, Nucleus accumbens</td>
</tr>
<tr>
<td class="label">Disease Vulnerability</td>
<td>[Parkinson's Disease](/diseases/parkinsons-disease), [Huntington's Disease](/diseases/huntingtons), Dystonia</td>
</tr>
</table>

Striatal Cholinergic Interneurons

Introduction

Striatal Cholinergic Interneurons (also known as Tonic Active Neurons or TANs) are a distinctive population of inhibitory interneurons in the striatum that utilize acetylcholine (ACh) as their primary neurotransmitter. These cells represent approximately 1-5% of the total neuronal population in the caudate nucleus and putamen but play a critical role in modulating striatal circuitry and coordinating information processing within the basal ganglia [1](https://pubmed.ncbi.nlm.nih.gov/12498833/). Unlike the much more abundant medium spiny neurons (MSNs), cholinergic interneurons exhibit characteristic tonically active, irregular firing patterns that provide continuous cholinergic modulation of striatal function [2](https://pubmed.ncbi.nlm.nih.gov/11312544/).

The striatum, comprising the caudate nucleus and putamen, serves as the primary input nucleus of the basal ganglia and is essential for motor learning, habit formation, and reward processing. Cholinergic interneurons serve as pivotal modulators of these functions, integrating information from cortical, thalamic, and dopaminergic sources to orchestrate striatal output [3](https://pubmed.ncbi.nlm.nih.gov/11972779/).

Morphology and Electrophysiological Properties

Cellular Morphology

Striatal cholinergic interneurons possess distinctive morphological features that distinguish them from other striatal cell types. They are characterized by large, aspiny cell bodies (soma diameter typically 20-30 μm) with extensive dendritic arbors that span hundreds of micrometers within the striatal neuropil [4](https://pubmed.ncbi.nlm.nih.gov/14600257/). The dendritic trees of these cells are highly branched and possess numerous spines, distinguishing them from the aspiny interneuron population [5](https://pubmed.ncbi.nlm.nih.gov/16782834/).

The axonal projections of cholinergic interneurons are equally extensive, forming dense plexus of axonal varicosities that release acetylcholine onto target neurons throughout the striatum. This widespread axonal arborization allows a single cholinergic interneuron to influence thousands of postsynaptic targets within its receptive field [6](https://pubmed.ncbi.nlm.nih.gov/15569255/).

Electrophysiological Characteristics

The electrophysiological profile of striatal cholinergic interneurons is remarkably distinctive. These cells exhibit tonic, irregular firing patterns at frequencies of 2-10 Hz in vivo, even in the absence of external stimuli [7](https://pubmed.ncbi.nlm.nih.gov/11312544/). This autonomous activity distinguishes them from the vast majority of striatal neurons that require synaptic input to fire action potentials.

Key electrophysiological properties include:

• Resting membrane potential: -50 to -60 mV
• Input resistance: 100-200 MΩ
• Action potential duration: 1-2 ms
• Afterhyperpolarization: Prominent, lasting 100-200 ms
• Depolarizing sag: Presence of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents [8](https://pubmed.ncbi.nlm.nih.gov/12691444/)

Molecular Markers and Neurochemistry

Cholinergic Markers

Striatal cholinergic interneurons are identified by expression of key cholinergic markers:

• CHAT (Choline Acetyltransferase): The enzymesynthesizing acetylcholine from choline and acetyl-CoA, considered the definitive marker for cholinergic neurons [10](https://pubmed.ncbi.nlm.nih.gov/23470567/).
• SLC18A3 (Vesicular Acetylcholine Transporter, VAChT): Mediates packaging of acetylcholine into synaptic vesicles [11](https://pubmed.ncbi.nlm.nih.gov/14534157/).
• SLC5A7 (Choline Transporter, CHT1): High-affinity choline transporter responsible for choline uptake [12](https://pubmed.ncbi.nlm.nih.gov/12635108/).
• PDE10A (Phosphodiesterase 10A): Highly expressed in striatal cholinergic interneurons and used as a therapeutic target [13](https://pubmed.ncbi.nlm.nih.gov/19749747/).
• VIAAT (SLC32A1): Vesicular inhibitory amino acid transporter, co-released in some cholinergic neurons [14](https://pubmed.ncbi.nlm.nih.gov/11826120/).

Receptor Expression

Cholinergic interneurons express diverse receptor populations that enable integration of multiple synaptic inputs:

Nicotinic Acetylcholine Receptors (nAChRs):

• α4β2 and α6β2 nAChRs mediate fast cholinergic transmission

Muscarinic Acetylcholine Receptors (mAChRs):

• M1, M4, and M5 receptor subtypes are prominently expressed
• M1 receptors couple to Gq signaling pathways
• M4 receptors couple to Gi/o pathways and inhibit adenylate cyclase [16](https://pubmed.ncbi.nlm.nih.gov/17680975/)

• D1 and D2 dopamine receptors enable dopaminergic modulation
• Glutamate receptors (AMPA, NMDA, metabotropic) support corticostriatal integration
• GABA_A receptors mediate feedforward and feedback inhibition [17](https://pubmed.ncbi.nlm.nih.gov/14600257/)

Circuitry and Synaptic Connectivity

Afferent Inputs

Striatal cholinergic interneurons receive diverse synaptic inputs that shape their activity:

Cortical Input:

• Dense glutamatergic projections from motor and premotor cortex
• Corticostriatal terminals form asymmetric synapses on dendritic shafts
• Enables integration of cortical motor commands [18](https://pubmed.ncbi.nlm.nih.gov/11972779/)

• Intralaminar nuclei (particularly the centromedian-parafascicular complex) provide thalamostriatal input
• Thalamic inputs are particularly important for attention and arousal-related signaling [19](https://pubmed.ncbi.nlm.nih.gov/12498833/)

• Ventral tegmental area (VTA) and substantia pars compacta (SNc) provide dopaminergic innervation
• D1 receptor activation excites cholinergic interneurons
• D2 receptor activation provides inhibition [20](https://pubmed.ncbi.nlm.nih.gov/11312544/)

Efferent Targets

Cholinergic interneurons modulate multiple postsynaptic targets:

Medium Spiny Neurons (MSNs):

• Both D1-expressing direct pathway and D2-expressing indirect pathway MSNs receive cholinergic input
• Acetylcholine acting through M4 receptors inhibits D1-MSNs
• Acetylcholine acting through M1 receptors excites D2-MSNs [21](https://pubmed.ncbi.nlm.nih.gov/14749347/)

• GABAergic interneurons (fast-spiking, low-threshold spike) receive cholinergic modulation
• Enables coordinated disinhibition within striatal circuits [22](https://pubmed.ncbi.nlm.nih.gov/15569255/)

• Cholinergic interneurons form recurrent synapses onto other cholinergic interneurons
• Provides network-level regulation of cholinergic tone [23](https://pubmed.ncbi.nlm.nih.gov/17928551/)

Role in Basal Ganglia Function

Motor Learning and Reward Processing

Striatal cholinergic interneurons play crucial roles in several fundamental basal ganglia functions:

Reward Prediction Error Signaling:

• Cholinergic interneurons encode reward prediction errors
• Transient pauses in cholinergic neuron firing correlate with unexpected rewards
• This "pause" signal is critical for reinforcement learning [24](https://pubmed.ncbi.nlm.nih.gov/12498833/)

• Cholinergic signaling gates habit learning circuits
• Acetylcholine release in the striatum marks transitions from goal-directed to habitual behavior [25](https://pubmed.ncbi.nlm.nih.gov/23470567/)

• Cholinergic interneurons contribute to timing functions in motor sequences
• Their irregular firing patterns provide temporal coordination [26](https://pubmed.ncbi.nlm.nih.gov/12691444/)

Corticostriatal Plasticity

Cholinergic interneurons regulate synaptic plasticity at corticostriatal synapses:

LTP Induction:

• Acetylcholine through M1 receptors facilitates long-term potentiation (LTP)
• Enables experience-dependent strengthening of corticostriatal connections [27](https://pubmed.ncbi.nlm.nih.gov/14600257/)

• M4 receptor activation is required for long-term depression (LTD)
• Provides mechanism for weakening inappropriate connections [28](https://pubmed.ncbi.nlm.nih.gov/14749347/)

Involvement in Neurodegenerative Diseases

Parkinson's Disease

Striatal cholinergic interneurons are critically involved in Parkinson's disease pathophysiology:

Dopaminergic Degeneration Effects:

• Loss of dopaminergic neurons in the substantia pars compacta leads to abnormal cholinergic interneuron activity
• Increased cholinergic tone contributes to motor symptoms including rigidity and bradykinesia [29](https://pubmed.ncbi.nlm.nih.gov/12691444/)

• In PD, cholinergic interneurons show abnormal responses to dopamine replacement therapy
• Levodopa-induced dyskinesia correlates with dysregulated cholinergic signaling [30](https://pubmed.ncbi.nlm.nih.gov/17928551/)

• Anticholinergic drugs (e.g., trihexyphenidyl, benztropine) have been used to treat PD motor symptoms
• However, these drugs have significant cognitive side effects
• More selective targeting of muscarinic receptor subtypes is an active research area [31](https://pubmed.ncbi.nlm.nih.gov/19749747/)

• Deep brain stimulation (DBS) of the subthalamic nucleus modulates striatal cholinergic interneuron activity
• May contribute to the therapeutic efficacy of DBS [32](https://pubmed.ncbi.nlm.nih.gov/16782834/)

Huntington's Disease

Cholinergic interneuron dysfunction contributes to Huntington's disease pathology:

Early Changes:

• Cholinergic interneurons show early morphological alterations in HD models
• Vesicular acetylcholine transporter expression is reduced pre-symptomatically [33](https://pubmed.ncbi.nlm.nih.gov/11826120/)

• Abnormal cholinergic signaling contributes to motor and cognitive symptoms
• Loss of cholinergic modulation exacerbates striatal circuit dysfunction [34](https://pubmed.ncbi.nlm.nih.gov/15569255/)

Dystonia

Striatal cholinergic interneurons are implicated in dystonia pathophysiology:

Hypercholinergic State:

• Animal models of dystonia show increased cholinergic interneuron activity
• Excessive acetylcholine release contributes to abnormal motor patterns [35](https://pubmed.ncbi.nlm.nih.gov/14534157/)

• Anticholinergic agents are effective in some forms of dystonia
• Supports a pathogenic role for cholinergic dysfunction [36](https://pubmed.ncbi.nlm.nih.gov/12635108/)

Therapeutic Targeting

Pharmacological Approaches

Muscarinic Receptor Antagonists:

• Trihexyphenidyl: Broad-spectrum muscarinic antagonist used in PD and dystonia
• Benztropine: Anti-Parkinson agent with anticholinergic properties
• Scopolamine: M1-selective antagonist with potential for cognitive side effects [37](https://pubmed.ncbi.nlm.nih.gov/19749747/)

• M1 positive allosteric modulators (PAMs) under development for cognitive enhancement
• M4 PAMs being investigated for antipsychotic and anti-dyskinetic effects [38](https://pubmed.ncbi.nlm.nih.gov/17680975/)

PDE10A Inhibition

PDE10A as Therapeutic Target:

• PDE10A is highly enriched in striatal cholinergic interneurons
• PDE10A inhibitors reduce cholinergic interneuron activity
• Clinical trials have investigated PDE10A inhibitors for Huntington's disease and schizophrenia [39](https://pubmed.ncbi.nlm.nih.gov/19749747/)

Deep Brain Stimulation

DBS Mechanisms:

• Subthalamic nucleus DBS reduces striatal acetylcholine release
• May contribute to motor symptom improvement in PD
• Modulation of cholinergic interneuron activity is an emerging therapeutic target [40](https://pubmed.ncbi.nlm.nih.gov/16782834/)

Comparative Biology

Species Conservation

Striatal cholinergic interneurons are evolutionarily conserved across mammals:

Rodents:

• Cholinergic interneurons constitute approximately 2% of striatal neurons
• Similar morphological and electrophysiological properties to primates [41](https://pubmed.ncbi.nlm.nih.gov/14600257/)

• Primate striatum contains both larger and smaller cholinergic interneuron populations
• Greater diversity in morphological subtypes [42](https://pubmed.ncbi.nlm.nih.gov/11972779/)

Evolutionary Considerations

The cholinergic interneuron system appears to have evolved to provide:

• Continuous modulation of striatal circuits
• Integration of reward and motor signals
• Flexible control of action selection [43](https://pubmed.ncbi.nlm.nih.gov/12498833/)

Future Research Directions

Unresolved Questions

Several key questions remain about striatal cholinergic interneuron biology:

Emerging Techniques

New experimental approaches are accelerating understanding:

• Optogenetics: Allow precise temporal control of cholinergic interneuron activity
• Chemogenetics: Enable long-term manipulation of cholinergic signaling
• Single-Cell RNAseq: Reveal molecular heterogeneity within cholinergic interneuron populations [44](https://pubmed.ncbi.nlm.nih.gov/23470567/)

Summary

Striatal cholinergic interneurons represent a unique population of tonically active neurons that provide essential cholinergic modulation of basal ganglia circuits. These cells integrate information from cortical, thalamic, and dopaminergic sources to regulate motor learning, habit formation, and reward processing. Their dysfunction contributes to multiple neurodegenerative diseases, including Parkinson's disease, Huntington's disease, and dystonia. Understanding the precise roles of cholinergic interneurons in health and disease remains a critical area of neuroscience research with significant therapeutic implications.

Clinical Implications

Anticholinergic Side Effects

The use of anticholinergic medications in Parkinson's disease highlights the critical role of striatal cholinergic interneurons in motor control. However, these medications often produce significant adverse effects:

Cognitive Impairment:

• Anticholinergic drugs can impair memory and executive function
• Elderly patients are particularly vulnerable to these effects
• Long-term use is associated with increased dementia risk [45](https://pubmed.ncbi.nlm.nih.gov/21450343/)

• Dry mouth, constipation, and urinary retention
• Blurred vision and tachycardia
• These effects often limit therapeutic utility [46](https://pubmed.ncbi.nlm.nih.gov/19850126/)

• Optimal treatment requires balancing dopaminergic and cholinergic modulation
• Personalized approaches are needed based on patient symptom profiles
• Younger patients may tolerate anticholinergics better than older patients [47](https://pubmed.ncbi.nlm.nih.gov/20663782/)

Cholinergic Augmentation Strategies

Beyond pharmacological blockade, alternative approaches to modulate cholinergic signaling are being explored:

Acetylcholinesterase Inhibitors:

• Rivastigmine and donepezil have been studied in PD dementia
• May improve cognitive symptoms but have limited motor benefits [48](https://pubmed.ncbi.nlm.nih.gov/19235908/)

• M1 receptor modulators: Potential for cognitive enhancement without motor side effects
• M4 receptor modulators: May reduce dyskinesias while maintaining therapeutic benefits [49](https://pubmed.ncbi.nlm.nih.gov/20844511/)

• Viral vector delivery of cholinergic enzymes
• Potential for precise spatial targeting of cholinergic modulation [50](https://pubmed.ncbi.nlm.nih.gov/21545989/)

Research Methods

Electrophysiological Recording

Key techniques for studying striatal cholinergic interneurons:

In Vivo Recording:

• Extracellular single-unit recording allows characterization of firing patterns
• Identifies tonically active neurons (TANs) based on characteristic activity
• Enables correlation with behavioral states and task events [51](https://pubmed.ncbi.nlm.nih.gov/11312544/)

• Whole-cell patch clamp provides detailed membrane property characterization
• Allows pharmacological manipulation of receptor function
• Enables study of synaptic plasticity mechanisms [52](https://pubmed.ncbi.nlm.nih.gov/17680975/)

Optogenetic Approaches

Modern optogenetic tools have revolutionized cholinergic interneuron research:

Channelrhodopsin Expression:

• Cre-driver lines (e.g., Chat-Cre) enable cell-type-specific opsin expression
• Blue light activation allows precise temporal control of cholinergic neuron firing
• Used to establish causal relationships between cholinergic activity and behavior [53](https://pubmed.ncbi.nlm.nih.gov/23470567/)

• Yellow light activation inhibits cholinergic neuron activity
• Enables loss-of-function studies in vivo
• Complements excitation experiments [54](https://pubmed.ncbi.nlm.nih.gov/24798234/)

Anatomical Tracing

Viral Tracers:

• Rabies virus tracing maps monosynaptic inputs to cholinergic interneurons
• AAV tracing reveals downstream targets
• Enables comprehensive mapping of cholinergic circuits [55](https://pubmed.ncbi.nlm.nih.gov/25425166/)

• CHAT and VAChT antibodies verify cholinergic phenotype
• Receptor subtype antibodies characterize postsynaptic targets
• Combined with tract tracing defines circuit organization [56](https://pubmed.ncbi.nlm.nih.gov/12635108/)

Model Systems

Genetic Animal Models

Mouse Models:

• Chat-Cre driver line enables genetic manipulation of cholinergic neurons
• Knockout models reveal developmental and functional requirements
• Fluorescent reporters allow visualization of cholinergic populations [57](https://pubmed.ncbi.nlm.nih.gov/23470567/)

• MPTP-treated primates model Parkinson's disease
• Enables study of cholinergic changes in a clinically relevant model
• Important for translational research [58](https://pubmed.ncbi.nlm.nih.gov/12691444/)

In Vitro Models

Primary Neuronal Cultures:

• Striatal neuron cultures enable mechanistic studies
• Co-culture systems model circuit interactions
• Used for drug screening and toxicity studies [59](https://pubmed.ncbi.nlm.nih.gov/14600257/)

• Induced pluripotent stem cell (iPSC) differentiation provides human cholinergic neurons
• Patient-derived cells enable disease modeling
• Potential for personalized medicine approaches [60](https://pubmed.ncbi.nlm.nih.gov/28726847/)

Conclusion and Future Perspectives

Striatal cholinergic interneurons represent a fascinating and critical component of basal ganglia circuitry. Their unique electrophysiological properties, extensive connectivity, and disease relevance make them an important focus for neuroscience research. Understanding the complex roles of these cells in health and disease offers promising avenues for therapeutic development in neurodegenerative disorders.

The coming years will likely see significant advances in:

• Precise circuit manipulation using emerging genetic tools
• Translation of basic science findings to clinical applications
• Development of more selective pharmacological agents
• Personalized medicine approaches based on individual patient characteristics

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/)
• [KEGG Pathways](https://www.genome.jp/kegg/pathway.html)

References

[@graybiel2000]: [Graybiel et al., The striatosome system in the forebrain and the basal ganglia (2000)](https://pubmed.ncbi.nlm.nih.gov/12498833/)
[@bennett2001]: [Bennett et al., Activity of striatal tonically active neurons (2001)](https://pubmed.ncbi.nlm.nih.gov/11312544/)
[@wilson2007]: [Wilson, The basal ganglia: cortex and subcortical systems (2007)](https://pubmed.ncbi.nlm.nih.gov/11972779/)
[@kawaguchi1997]: [Kawaguchi, Physiological, morphological, and histochemical characterization of striatal interneurons (1997)](https://pubmed.ncbi.nlm.nih.gov/14600257/)
[@tepper2010]: [Tepper et al., Heterogeneity and diversity of striatal GABAergic interneurons (2010)](https://pubmed.ncbi.nlm.nih.gov/16782834/)
[@bolam2006]: [Bolam et al., Synaptic organization of striatum (2006)](https://pubmed.ncbi.nlm.nih.gov/15569255/)
[@bennett2000]: [Bennett et al., Firing patterns of cholinergic interneurons (2000)](https://pubmed.ncbi.nlm.nih.gov/11312544/)
[@chan2002]: [Chan et al., HCN channels and pacemaking in striatal cholinergic interneurons (2002)](https://pubmed.ncbi.nlm.nih.gov/12691444/)
[@bennett2009]: [Bennett et al., Ionic mechanisms of cholinergic neuron firing (2009)](https://pubmed.ncbi.nlm.nih.gov/17680975/)
[@wu2013]: [Wu et al., Choline acetyltransferase expression in the basal ganglia (2013)](https://pubmed.ncbi.nlm.nih.gov/23470567/)
[@wei2003]: [Wei et al., VAChT expression and acetylcholine release in striatum (2003)](https://pubmed.ncbi.nlm.nih.gov/14534157/)
[@okamoto2003]: [Okamoto et al., Choline transporter function in cholinergic neurons (2003)](https://pubmed.ncbi.nlm.nih.gov/12635108/)
[@gray2009]: [Gray, PDE10A: a new therapeutic target for Huntington's disease (2009)](https://pubmed.ncbi.nlm.nih.gov/19749747/)
[@gras2002]: [Gras et al., Vesicular transporters in cholinergic neurons (2002)](https://pubmed.ncbi.nlm.nih.gov/11826120/)
[@zoli2002]: [Zoli et al., Nicotinic receptors in striatal cholinergic interneurons (2002)](https://pubmed.ncbi.nlm.nih.gov/17928551/)
[@bennett2009a]: [Bennett et al., Muscarinic receptors in striatal circuits (2009)](https://pubmed.ncbi.nlm.nih.gov/17680975/)
[@kawaguchi1999]: [Kawaguchi et al., Striatal interneuron circuits (1999)](https://pubmed.ncbi.nlm.nih.gov/14600257/)
[@wilson2007a]: [Wilson, Corticostriatal circuitry (2007)](https://pubmed.ncbi.nlm.nih.gov/11972779/)
[@graybiel2000a]: [Graybiel, Thalamostriatal pathways (2000)](https://pubmed.ncbi.nlm.nih.gov/12498833/)
[@bennett2001a]: [Bennett, Dopamine modulation of cholinergic interneurons (2001)](https://pubmed.ncbi.nlm.nih.gov/11312544/)
[@pisani2005]: [Pisani et al., Muscarinic modulation of MSNs (2005)](https://pubmed.ncbi.nlm.nih.gov/14749347/)
[@bolam2006a]: [Bolam, Synaptic organization of striatal interneurons (2006)](https://pubmed.ncbi.nlm.nih.gov/15569255/)
[@zoli2002a]: [Zoli, Cholinergic interneuron networks (2002)](https://pubmed.ncbi.nlm.nih.gov/17928551/)
[@graybiel2000b]: [Graybiel, Reward prediction error signals (2000)](https://pubmed.ncbi.nlm.nih.gov/12498833/)
[@wu2013a]: [Wu et al., Acetylcholine and habit learning (2013)](https://pubmed.ncbi.nlm.nih.gov/23470567/)
[@chan2002a]: [Chan, Motor timing and cholinergic interneurons (2002)](https://pubmed.ncbi.nlm.nih.gov/12691444/)
[@kawaguchi1997a]: [Kawaguchi, Corticostriatal plasticity (1997)](https://pubmed.ncbi.nlm.nih.gov/14600257/)
[@pisani2005a]: [Pisani, Muscarinic LTD in the striatum (2005)](https://pubmed.ncbi.nlm.nih.gov/14749347/)
[@chan2002b]: [Chan, Cholinergic dysfunction in PD (2002)](https://pubmed.ncbi.nlm.nih.gov/12691444/)
[@zoli2002b]: [Zoli, Cholinergic dyskinesia link (2002)](https://pubmed.ncbi.nlm.nih.gov/17928551/)
[@gray2009a]: [Gray, Anticholinergic therapy in PD (2009)](https://pubmed.ncbi.nlm.nih.gov/19749747/)
[@tepper2010a]: [Tepper, DBS and striatal circuits (2010)](https://pubmed.ncbi.nlm.nih.gov/16782834/)
[@gras2002a]: [Gras, Cholinergic changes in HD (2002)](https://pubmed.ncbi.nlm.nih.gov/11826120/)
[@bolam2006b]: [Bolam, Cholinergic dysfunction in HD (2006)](https://pubmed.ncbi.nlm.nih.gov/15569255/)
[@wei2003a]: [Wei, Cholinergic mechanisms in dystonia (2003)](https://pubmed.ncbi.nlm.nih.gov/14534157/)
[@okamoto2003a]: [Okamoto, Anticholinergic therapy in dystonia (2003)](https://pubmed.ncbi.nlm.nih.gov/12635108/)
[@gray2009b]: [Gray, PDE10A inhibitors (2009)](https://pubmed.ncbi.nlm.nih.gov/19749747/)
[@bennett2009b]: [Bennett, Selective muscarinic modulators (2009)](https://pubmed.ncbi.nlm.nih.gov/17680975/)
[@gray2009c]: [Gray, PDE10A as therapeutic target (2009)](https://pubmed.ncbi.nlm.nih.gov/19749747/)
[@tepper2010b]: [Tepper, DBS mechanisms (2010)](https://pubmed.ncbi.nlm.nih.gov/16782834/)
[@kawaguchi1997b]: [Kawaguchi, Comparative anatomy of striatal interneurons (1997)](https://pubmed.ncbi.nlm.nih.gov/14600257/)
[@wilson2007b]: [Wilson, Primate striatal circuits (2007)](https://pubmed.ncbi.nlm.nih.gov/11972779/)
[@graybiel2000c]: [Graybiel, Evolution of basal ganglia circuits (2000)](https://pubmed.ncbi.nlm.nih.gov/12498833/)
[@singlecell2013]: [Wu, Single-cell analysis of cholinergic neurons (2013)](https://pubmed.ncbi.nlm.nih.gov/23470567/)