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Institute for Neuroscience and Cardiovascular Research
University of Edinburgh
Despite the attention devoted to synapses, neurons can also release neurotransmitters away from presynaptic terminals, such as along axonal hotspots. Non-synaptic neurotransmission is implicated in the function of many neural circuits, but we have a poor understanding of the underlying molecular mechanisms and of how it impacts the nervous system. The Almeida Lab uses the zebrafish model organism to study...
Axonal mechanisms
Axonal mechanisms
Neurotransmitters are released at synapses with nanoscopic and millisecond precision, conferred by an array of specialized molecular machinery that couples action potentials to membrane fusion .
What machinery do axons use to release neurotransmitters non-synaptically? How are axonal release hotspots specified? How does neuronal activity regulate axonal release?
Cellular Responses
Cellular Responses
Axon-released neurotransmitters may reach nearby neurons or glia, which express many high-affinity / metabotropic neurotransmitter receptors, and regulate their physiology and circuit function.
Which cells respond to axonal neurotransmitter release?
Which receptors mediate these responses?
Axon-myelin interactions
Axon-myelin interactions
We found that axonal vesicle fusion mediates axon-oligodendrocyte communication and promotes the development of myelin, which insulates axons to speed up electrical signals.
Which myelin receptors sense neurotransmitters, and how do they induce myelin remodelling?
Can we repurpose this signaling to repair myelin when it is damaged, for example in multiple sclerosis?
SNAREopathies
SNAREopathies
Non-synaptic neurotransmitter release requires proteins typically thought of as "synaptic", such as SNARE proteins responsible for membrane fusion. SNARE mutations cause a distinct class of neurodevelopmental disorders termed SNAREopathies, with a complex and poorly understood disease aetiology.
Is non-synaptic transmission dysregulated in neurodevelopmental disorders?
To address these questions, we exploit the power of the zebrafish model organism.
Studying neurotransmission in living neurons embedded in their circuits is challenging!
Zebrafish are genetically conserved vertebrates whose small, transparent embryos have a simple but functional nervous system by 24 hours after fertilization. They develop quickly and externally, making them ideal for live-imaging neurons (and glia) in real time, in a completely non-invasive manner.
We draw on advanced genome editing and confocal live microscopy for structural and functional imaging of zebrafish cells and circuits. We are happy to share our reagents and keen to contribute to the zebrafish genetic toolkit - check out our fast, cloning-free, knock-in method.
Our research is supported by generous funders & collaborators:
Our research is supported by generous funders & collaborators:
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Darwin Trust
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