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Related Concept Videos

Chemical Synapses01:26

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Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
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Neurochemical transmission, the conduction of electrical impulses between neurons mediated by neurotransmitters, plays a vital role in various physiological processes. Autonomic drugs exert their effects by modulating neurotransmission within the autonomic nervous system. For instance, drugs such as hemicholinium block the precursor uptake necessary for synthesizing acetylcholine, an essential autonomic neurotransmitter. Following synthesis, neurotransmitters are stored in vesicles. Metyrosine...
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Neurons communicate at synapses, or junctions, to excite or inhibit the activity of other neurons or target cells, such as muscles. Synapses may be chemical or electrical.
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The Synapse02:47

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Neurons communicate with one another by passing on their electrical signals to other neurons. A synapse is the location where two neurons meet to exchange signals. At the synapse, the neuron that sends the signal is called the presynaptic cell, while the neuron that receives the message is called the postsynaptic cell. Note that most neurons can be both presynaptic and postsynaptic, as they both transmit and receive information.
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Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

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Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
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Drugs exert their therapeutic effects by interacting with receptors, enzymes, or ion channels that are present throughout the human body. The strength and duration of the interaction between a drug and its target receptor are characterized by the selectivity and specificity of the drug. Selectivity refers to a drug's strong preference for its intended target over other targets. For instance, isoprenaline, a non-selective β-adrenergic agonist, interacts with both β1- and...
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Updated: Jun 23, 2025

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DART.2: bidirectional synaptic pharmacology with thousandfold cellular specificity.

Brenda C Shields1, Haidun Yan1,2, Shaun S X Lim1

  • 1Department of Biomedical Engineering, Duke University, Durham, NC, USA.

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|June 14, 2024
PubMed
Summary
This summary is machine-generated.

Researchers developed DART.2 (drug acutely restricted by tethering), a novel cell-specific pharmacology technology. This innovation allows precise drug delivery to targeted cells, minimizing off-target effects for advanced neuroscience research.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Cellular Biology

Background:

  • Precision pharmacology seeks to precisely control cellular interactions within tissues.
  • Existing methods often lack the specificity required for complex biological systems.

Purpose of the Study:

  • Introduce DART.2 (drug acutely restricted by tethering), a second-generation cell-specific pharmacology technology.
  • Enhance cellular specificity for targeted drug delivery and minimize off-target effects.
  • Develop brain-wide dosing and quantification methods.

Main Methods:

  • Developed DART.2 technology for optimized cellular specificity (up to 3,000-fold in 15 minutes).
  • Introduced brain-wide dosing and tracer reagents for dose quantification.
  • Described four novel pharmaceuticals targeting excitatory and inhibitory postsynaptic receptors.

Main Results:

  • Demonstrated high cellular specificity of DART.2 across multiple mouse brain regions (cerebellum, striatum, visual cortex, retina).
  • Showcased the versatility of DART.2 with drugs targeting postsynaptic receptors.
  • Found that blocking inhibitory inputs to dopamine neurons in the ventral tegmental area accelerates locomotion.

Conclusions:

  • DART.2 offers unprecedented precision for cell-specific pharmacology.
  • The technology enables bidirectional perturbation of chemical synapses with intersectional precision.
  • Findings in the ventral tegmental area provide new insights into dopamine neuron regulation of locomotion.