ArticleProceedings of the National Academy of Sciences of the United States of America2012
Elimination of the vesicular acetylcholine transporter in the forebrain causes hyperactivity and deficits in spatial memory and long-term potentiation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 69 citations in OpenAlex.
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- Spared cognitive and social function following perinatal ablation of ATRX despite transient microglia dysregulation.Scientific reports · 2026Article
- Cholinergic modulation of hippocampal CA1 pyramidal cell excitability in ArxExperimental neurology · 2026Article
- Characterization of a novel transgenic mouse model to investigate brain-wide activation of astrocyte Gq signaling.Lab animal · 2025Article
- A Longitudinal Study of Sex Differences in a TDP-43 Mouse Model Reveals STI1 Regulation of TDP-43 Proteinopathy and Motor Deficits.Journal of neurochemistry · 2025Article
- Exogenous Administration of Delta-9-Tetrahydrocannabinol Affects Adult Hippocampal Neurotransmission in Female Wistar Rats.International journal of molecular sciences · 2025Article
- Imaging the Vesicular Acetylcholine Transporter in Schizophrenia: A Positron Emission Tomography Study Using [Biological psychiatry · 2024Article
- Cholinergic modulation of rearing in rats performing a spatial memory task.The European journal of neuroscience · 2024Article
- A consistent map in the medial entorhinal cortex supports spatial memory.Nature communications · 2024Article
- SRF-deficient astrocytes provide neuroprotection in mouse models of excitotoxicity and neurodegeneration.eLife · 2024Article
- A consistent map in the medial entorhinal cortex supports spatial memory.bioRxiv : the preprint server for biology · 2023Article
- Cholinergic neurons in the basal forebrain are involved in behavioral abnormalities associated with Cul3 deficiency: Role of prefrontal cortex projections in cognitive deficits.Translational psychiatry · 2023Article
- Presynaptic Congenital Myasthenic Syndromes: Understanding Clinical Phenotypes through In vivo Models.Journal of neuromuscular diseases · 2023Review
- Nicotinic Acetylcholine Receptors Expressed by Striatal Interneurons Inhibit Striatal Activity and Control Striatal-Dependent Behaviors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Reduction of acetylcholine in the hippocampus of hippocampal cholinergic neurostimulating peptide precursor protein knockout mice.Scientific reports · 2021Article
- Adolescent Ethanol Exposure Alters Cholinergic Function and Apical Dendritic Branching Within the Orbital Frontal Cortex.Neuroscience · 2021Article
- Deficits in the vesicular acetylcholine transporter alter lifespan and behavior in adult Drosophila melanogaster.Neurochemistry international · 2020Article
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- 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
- Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Basal forebrain cholinergic neurons, which innervate the hippocampus and cortex, have been implicated in many forms of cognitive function. Immunolesion-based methods in animal models have been widely used to study the role of acetylcholine (ACh) neurotransmission in these processes, with variable results. Cholinergic neurons have been shown to release both glutamate and ACh, making it difficult to deduce the specific contribution of each neurotransmitter on cognition when neurons are eliminated. Understanding the precise roles of ACh in learning and memory is critical because drugs that preserve ACh are used as treatment for cognitive deficits. It is therefore important to define which cholinergic-dependent behaviors could be improved pharmacologically. Here we investigate the contributions of forebrain ACh on hippocampal synaptic plasticity and cognitive behavior by selective elimination of the vesicular ACh transporter, which interferes with synaptic storage and release of ACh. We show that elimination of vesicular ACh transporter in the hippocampus results in deficits in long-term potentiation and causes selective deficits in spatial memory. Moreover, decreased cholinergic tone in the forebrain is linked to hyperactivity, without changes in anxiety or depression-related behavior. These data uncover the specific contribution of forebrain cholinergic tone for synaptic plasticity and behavior. Moreover, these experiments define specific cognitive functions that could be targeted by cholinergic replacement therapy.
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