ArticleeNeuro
Level of hM4D(Gi) DREADD Expression Determines Inhibitory and Neurotoxic Effects in the Hippocampus.
Article in eNeuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Article
- Next-generation chemogenetic inhibition using a brain-permeant non-prescription agent.Signal transduction and targeted therapy · 2026Article
- Prelimbic cortex layer 5 GABAergic neurons mediate chronic pain and memory impairment by regulating excitatory/inhibitory imbalance.The journal of headache and pain · 2026Article
- Genetic manipulation technologies for precise cellular control: a comparative review of five approaches.Frontiers in bioengineering and biotechnology · 2026Review
- Activation of the zona incerta GABAergic circuit for the treatment of pain hypersensitivity in Parkinson's disease mice model.The journal of headache and pain · 2025Article
- Hypothalamic Orexin Projections to the Hippocampal CA1 Region Alleviate Cognitive and Synaptic Plasticity Impairments Induced by Blue Light Exposure.CNS neuroscience & therapeutics · 2025Article
- Transient DREADD Manipulation of the Dorsal Dentate Gyrus in Rats Impairs Initial Learning of Place-Outcome Associations.Hippocampus · 2025Article
- Investigations on the Ability of the Insular Cortex to Process Peripheral Immunosuppression.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- Article
- Prefrontal cortex neurons encode ambient light intensity differentially across regions and layers.Nature communications · 2024Article
- Chemogenetic activation of mammalian brain neurons expressing insect Ionotropic Receptors by systemic ligand precursor administration.Communications biology · 2024Article
- Perturbing cortical networks:Frontiers in neuroscience · 2024Article
- Comparison of three DREADD agonists acting on Gq-DREADDs in the ventral tegmental area to alter locomotor activity in tyrosine hydroxylase:Cre male and female rats.Behavioural brain research · 2023Article
- Application of optogenetic glial cells to neuron-glial communication.Frontiers in cellular neuroscience · 2023Review
- Applications of chemogenetics in non-human primates.Current opinion in pharmacology · 2022Review
- Chemogenetic Seizure Control with Clozapine and the Novel Ligand JHU37160 Outperforms the Effects of Levetiracetam in the Intrahippocampal Kainic Acid Mouse Model.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Selective neuromodulation using designer receptors exclusively activated by designer drugs (DREADDs) has become an increasingly important research tool, as well as an emerging therapeutic approach. However, the safety profile of DREADD expression is unknown. Here, different titers of adeno-associated viral (AAV) vector were administered in an attempt to vary total expression levels of the inhibitory DREADD hM4D(Gi) in excitatory hippocampal neurons. Male Sprague Dawley rats were injected with AAV2/7 encoding DREADD-mCherry, DREADD, or mCherry. Pronounced neuronal loss and neuroinflammatory reactions were observed after transduction with the high titer DREADD AAV, which also resulted in the highest DREADD expression levels. No such effects were observed in the mCherry control group, despite an equally high titer, nor in conditions where lower viral vector titers were injected. In the high titer DREADD conditions, dentate gyrus (DG) evoked potentials were inhibited on clozapine-induced activation of hM4D(Gi), while in low titer conditions DG evoked potentials were enhanced. Recordings of single neuronal activity nevertheless indicated a reduction in spontaneous firing of granule cell layer neurons. Our results indicate that prolonged, high levels of DREADD expression can have neurotoxic effects and that chemogenetic suppression of excitatory hippocampal neurons can paradoxically enhance DG evoked potentials.
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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.