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Adeno-associated Virus-mediated Transgene Expression in Genetically Defined Neurons of the Spinal Cord
Published on: May 12, 2018
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Neuronal transgene expression in dominant-negative SNARE mice
Takumi Fujita1, Michael J Chen2, Baoman Li2
1Center for Translational Neuromedicine, University of Rochester Medical School, Rochester, New York 14642 nedergaard@urmc.rochester.edu Takumi_Fujita@urmc.rochester.edu.
Summary
A new study reveals that a widely used genetic tool (dnSNARE) to study astrocyte signaling is also expressed in neurons. This finding questions the role of astrocytes in neurotransmission via gliotransmitter release.
Area of Science:
- Neuroscience
- Cellular Biology
- Neurophysiology
Background:
- Transgenic mouse models have advanced neuroglia signaling research.
- Astrocyte vesicular release of gliotransmitters, studied using dominant-negative SNARE (dnSNARE) overexpression, was linked to neuronal functions.
- A key assumption was dnSNARE expression specificity to astrocytes.
Purpose of the Study:
- To investigate the expression pattern of the dnSNARE transgene.
- To determine the impact of dnSNARE expression on neuronal activity.
- To re-evaluate the evidence for astrocyte involvement in neurotransmission via gliotransmitter release.
Main Methods:
- Generation and analysis of dnSNARE transgenic mice.
- Assessment of transgene expression in cortical neurons and astrocytes.
- Electrophysiological recordings to measure cortical neuron activity.
Main Results:
- Widespread expression of the dnSNARE transgene was found in cortical neurons, not exclusively in astrocytes.
- Cortical neuron activity was reversibly suppressed in dnSNARE mice.
- This indicates potential confounding effects of neuronal dnSNARE expression.
Conclusions:
- The premise of astrocyte-specific dnSNARE expression is invalidated.
- Findings necessitate independent validation of astrocytic functions attributed to dnSNARE mice.
- Evidence supporting SNARE-dependent vesicular gliotransmitter release from astrocytes is questioned.
