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Related Concept Videos

Chemical Synapses01:26

Chemical Synapses

Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory organs,...
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

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...
Chemical Synapses01:26

Chemical Synapses

Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Integration of Synaptic Events01:28

Integration of Synaptic Events

Synaptic integration mainly includes the summation of graded potentials. Graded potentials, regardless of their type, cause subtle alterations in membrane voltage, resulting in either depolarization or hyperpolarization. These incremental changes, when combined or summed, can propel the neuron toward its threshold. Consider, for example, a membrane experiencing a +15 mV shift, causing it to depolarize from -70 mV to -55 mV. In this scenario, graded potentials govern the membrane's ability to...

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Related Experiment Video

Updated: Jun 23, 2026

Quantifying Spontaneous Ca2+ Fluxes and their Downstream Effects in Primary Mouse Midbrain Neurons
06:54

Quantifying Spontaneous Ca2+ Fluxes and their Downstream Effects in Primary Mouse Midbrain Neurons

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Resolving synaptic events using subsynaptically targeted GCaMP8 variants.

Jiawen Chen1,2, Junhao Lin1, Kaikai He1,2

  • 1University of Southern California, Department of Neurobiology, Los Angeles, CA USA.

Biorxiv : the Preprint Server for Biology
|July 4, 2025
PubMed
Summary
This summary is machine-generated.

Next-generation genetically encoded calcium indicators (GCaMP8) and analysis software (CaFire) now match chemical dyes and electrophysiology in speed and sensitivity for synaptic calcium imaging.

Keywords:
DrosophilaGCaMPcalcium imagingneuromuscular junctionsynapse

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Quantifying Spontaneous Ca2+ Fluxes and their Downstream Effects in Primary Mouse Midbrain Neurons
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Subcellular Imaging of Neuronal Calcium Handling In Vivo
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Subcellular Imaging of Neuronal Calcium Handling In Vivo

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Genetically encoded calcium indicators (like GCaMP) are crucial for visualizing neural activity.
  • Previous GCaMP versions had limitations in speed and sensitivity, especially at synaptic compartments, compared to chemical dyes and electrophysiology.
  • These limitations hindered detailed analysis of synaptic calcium dynamics.

Purpose of the Study:

  • To engineer next-generation GCaMP8-based indicators with improved speed and sensitivity for synaptic calcium imaging.
  • To develop a novel analysis program for automated quantification of calcium signals.
  • To validate the performance of these new indicators and software at the Drosophila neuromuscular junction.

Main Methods:

  • Engineering and validation of GCaMP8 variants targeted to presynaptic boutons, active zones, and postsynaptic compartments.
  • Development of a Python-based analysis program, CaFire, for automated quantification of evoked and spontaneous calcium signals.
  • Ratiometric imaging and comparison with chemical dyes and electrophysiological recordings at the Drosophila neuromuscular junction.

Main Results:

  • Engineered GCaMP8 sensors demonstrated superior performance compared to previous versions.
  • A ratiometric presynaptic GCaMP8m sensor accurately captured presynaptic calcium changes with high sensitivity and kinetics comparable to chemical dyes.
  • A postsynaptic GCaMP8m sensor detected quantal events with temporal and signal resolution rivaling electrophysiology.

Conclusions:

  • Next-generation GCaMP8 sensors, when targeted to synaptic compartments, achieve speed and sensitivity comparable to traditional methods.
  • The CaFire software enables automated and precise quantification of synaptic calcium signals.
  • These advancements provide powerful tools for resolving fast calcium dynamics at synapses.