ArticlePLoS biology2011
Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission.
Article in PLoS biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 91 citations in OpenAlex.
- The Novel Functions of M4 Muscarinic Receptors.Physiological research · 2025Review
- Altered Vesicular Acetylcholine Transporter Expression Regulates Acetylcholine Abundance in the Brain of Drosophila melanogaster.Journal of neurochemistry · 2025Article
- Accumbal Dopamine and Acetylcholine Dynamics during Psychostimulant Sensitization.bioRxiv : the preprint server for biology · 2025Article
- The human VGLUT3-pT8I mutation elicits uneven striatal DA signaling, food or drug maladaptive consumption in male mice.Nature communications · 2024Article
- Article
- Continuous cholinergic-dopaminergic updating in the nucleus accumbens underlies approaches to reward-predicting cues.Nature communications · 2022Article
- Functional dissociation of behavioral effects from acetylcholine and glutamate released from cholinergic striatal interneurons.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Nanoscopic distribution of VAChT and VGLUT3 in striatal cholinergic varicosities suggests colocalization and segregation of the two transporters in synaptic vesicles.Frontiers in molecular neuroscience · 2022Article
- Vesicular Acetylcholine Transporter Alters Cholinergic Tone and Synaptic Plasticity in DYT1 Dystonia.Movement disorders : official journal of the Movement Disorder Society · 2021Article
- Long-term endogenous acetylcholine deficiency potentiates pulmonary inflammation in a murine model of elastase-induced emphysema.Scientific reports · 2021Article
- Two Players in the Field: Hierarchical Model of Interaction between the Dopamine and Acetylcholine Signaling Systems in the Striatum.Biomedicines · 2021Review
- Cholinergic dysfunction in the dorsal striatum promotes habit formation and maladaptive eating.The Journal of clinical investigation · 2020Article
- Increased levels of Stress-inducible phosphoprotein-1 accelerates amyloid-β deposition in a mouse model of Alzheimer's disease.Acta neuropathologica communications · 2020Article
- Deficits in the vesicular acetylcholine transporter alter lifespan and behavior in adult Drosophila melanogaster.Neurochemistry international · 2020Article
- Impact of perinatal hypoxia on the developing brain.Physiological research · 2020Review
- Article
- Altered motor, anxiety-related and attentional task performance at baseline associate with multiple gene copies of the vesicular acetylcholine transporter and related protein overexpression in ChAT::Cre+ rats.Brain structure & function · 2019Article
- Cholinergic modulation of striatal microcircuits.The European journal of neuroscience · 2019Review
- Dual-transmitter systems regulating arousal, attention, learning and memory.Neuroscience and biobehavioral reviews · 2018Review
- Cholinergic Mechanisms of Target Oddball Stimuli Detection: The Late "P300-Like" Event-Related Potential in Rats.Neural plasticity · 2018Article
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Authors and funding
12 authors at 2 institutions in 4 countries.
Funding
Abstract
Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward. These neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles. Consequently cholinergic neurons can release both neurotransmitters, making it difficult to discern their individual contributions for the regulation of striatal functions. Here we have dissected the specific roles of acetylcholine release for striatal-dependent behaviour in mice by selective elimination of the vesicular acetylcholine transporter (VAChT) from striatal cholinergic neurons. Analysis of several behavioural parameters indicates that elimination of VAChT had only marginal consequences in striatum-related tasks and did not affect spontaneous locomotion, cocaine-induced hyperactivity, or its reward properties. However, dopaminergic sensitivity of medium spiny neurons (MSN) and the behavioural outputs in response to direct dopaminergic agonists were enhanced, likely due to increased expression/function of dopamine receptors in the striatum. These observations indicate that previous functions attributed to striatal cholinergic neurons in spontaneous locomotor activity and in the rewarding responses to cocaine are mediated by glutamate and not by acetylcholine release. Our experiments demonstrate how one population of neurons can use two distinct neurotransmitters to differentially regulate a given circuitry. The data also raise the possibility of using VAChT as a target to boost dopaminergic function and decrease high striatal cholinergic activity, common neurochemical alterations in individuals affected with Parkinson's disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.