ArticleNature methods2024
DART.2: bidirectional synaptic pharmacology with thousandfold cellular specificity.
Article in Nature methods, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Article
- A TMEM63B variant with enhanced mechanosensitive channel activity and acquired lipid scramblase function.The Journal of general physiology · 2026Article
- Discerning protein pools by selective staining with self-labeling tags.FEBS letters · 2026Review
- A cysteine reactive chloroalkane probe enables HaloTag ligation for downstream chemical proteomics analysis.RSC chemical biology · 2026Article
- Motor-to-Limbic Design of Direct Synaptic Communication between Dopamine Neurons in the Midbrain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Hippocampal Place Cells with NMDARs Do Not Require Excitation and Inhibition to Be Reciprocally Tuned.bioRxiv : the preprint server for biology · 2026Article
- Synthesis of Benzo[JACS Au · 2026Article
- A chemogenetic approach for temporal and cell-specific activation of endogenous GPCRs in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A general one-step protocol to generate impermeable fluorescent HaloTag substrates for in situ live cell application and super-resolution imaging.Nature communications · 2026Article
- Astrocytes as Therapeutic Targets in Neurodegenerative Disorders.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Behavioral state and stimulus strength regulate the role of somatostatin interneurons in stabilizing network activity.Cell reports · 2025Article
- Principles and Design of Molecular Tools for Sensing and Perturbing Cell Surface Receptor Activity.Chemical reviews · 2025Review
- How Dopamine Enables Learning from Aversion.Current opinion in behavioral sciences · 2025Article
- The role of dorsal raphe nucleus neuropeptides in reward and aversion.Frontiers in behavioral neuroscience · 2025Review
- Natural phasic inhibition of dopamine neurons signals cognitive rigidity.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
22 authors.
Funding
Abstract
Precision pharmacology aims to manipulate specific cellular interactions within complex tissues. In this pursuit, we introduce DART.2 (drug acutely restricted by tethering), a second-generation cell-specific pharmacology technology. The core advance is optimized cellular specificity-up to 3,000-fold in 15 min-enabling the targeted delivery of even epileptogenic drugs without off-target effects. Additionally, we introduce brain-wide dosing methods as an alternative to local cannulation and tracer reagents for brain-wide dose quantification. We describe four pharmaceuticals-two that antagonize excitatory and inhibitory postsynaptic receptors, and two that allosterically potentiate these receptors. Their versatility is showcased across multiple mouse-brain regions, including cerebellum, striatum, visual cortex and retina. Finally, in the ventral tegmental area, we find that blocking inhibitory inputs to dopamine neurons accelerates locomotion, contrasting with previous optogenetic and pharmacological findings. Beyond enabling the bidirectional perturbation of chemical synapses, these reagents offer intersectional precision-between genetically defined postsynaptic cells and neurotransmitter-defined presynaptic partners.
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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.