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Synapses maintain two forms of neurotransmitter release to support communication in the brain. First, evoked neurotransmitter release is triggered by the invasion of an action potential across en passant boutons that form along axons. The probability of evoked release (Pr) varies substantially across boutons, even within a single axon. Such heterogeneity is the result of differences in the probability of a single synaptic vesicle fusing (Pv) and in the number of vesicles available for immediate release, known as the readily-releasable pool (RRP). Spontaneous release (also known as a mini) is an important form of neurotransmission that occurs in the absence of action potentials. Because it cannot be triggered with electrical stimulation, much less is known about potential heterogeneity in the frequency of spontaneous release between boutons. We utilized a photostable and bright fluorescent indicator of glutamate release (iGluSnFR3) to quantify both spontaneous and evoked release at individual glutamatergic boutons. We found that the rate of spontaneous release is quite heterogenous at the level of individual boutons. Interestingly, when measuring both evoked and spontaneous release at single synapses, we found that boutons with the highest rates of spontaneous release also displayed the largest evoked responses.Using a new optical method to measure RRP at individual boutons, we found that this heterogeneity in spontaneous release was strongly correlated with the size of the RRP, but not related to Pv. We conclude that the RRP is a critical and dynamic aspect of synaptic strength that contributes to both evoked and spontaneous vesicle release. Significance StatementNeurotransmitter is released through two mechanisms: action potential-evoked and spontaneous vesicle fusion. It is unknown if some synapses specialize in either evoked or spontaneous release with an antagonistic relationship, or if the two forms of release coexist and have a cooperative relationship. We used a robust optical glutamate indicator to measure both forms of release at individual synapses. We found that the frequency of spontaneous release displays significant heterogeneity and is directly related to the size of the readily releasable pool of vesicles. This finding links both mechanisms of neurotransmitter release and suggests an important signaling mechanism to the postsynaptic neuron at individual synapses.
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Carrier gas triggered controlled biolistic delivery of DNA and protein therapeutics from metal–organic frameworks
We can alter the release kinetics of highly stabilized biomacromolecules in both skin and plant tissues to allow for either instant release or slow release simply by changing the typeof gas used in a pneumatic delivery jet.
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- Award ID(s):
- 2003534
- PAR ID:
- 10476437
- Publisher / Repository:
- RSC
- Date Published:
- Journal Name:
- Chemical Science
- Volume:
- 13
- Issue:
- 46
- ISSN:
- 2041-6520
- Page Range / eLocation ID:
- 13803 to 13814
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/D2SC04982A
