Parsing Out the Variability of Transmission at Central Synapses Using Optical Quantal Analysis

1. A quantal analysis of transmission at the identified molluscan synapse, V2-RPr1, was performed during development. The study was intended to determine the pre- and postsynaptic contributions to the marked changes in transmitter release described in the previous report. 2. The success of the quantal analysis was predicated on overcoming the problems associated with extending the quantal analysis technique to central synapses. This involved adopting the following strategies: 1) using a low-noise recording system coupled with electrical filtering; 2) establishing objective criteria for failures recognition; and 3) using three methods to determine the quantal content: amplitude histograms, failures analysis, and the coefficient of variation. 3. The correlation of the results obtained from an analysis of amplitude histograms and from failures analysis were highly significant (P less than 0.01) at all times studied. A similar significant correlation was observed between the failures method and the coefficient of variation methods. 4. The amplitude of the quantal unit declined progressively during development (range: 131-25 microV), in parallel with the decrease in the postsynaptic input resistance (range: 103-5 M omega). 5. At both frequencies of stimulation (0.02 and 0.2 Hz), there is an approximately 20-fold increase in quantal content over the period of the study. Frequency facilitation at the synapse is due to an increase in quantal content. 6. Possible structural correlates for the developmental increase in quantal content were discussed.

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Faculty Opinions recommendation of Facilitation at single synapses probed with optical quantal analysis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1007941.99962 ◽

2002 ◽

Author(s):

Kevan A Martin

Keyword(s):

Quantal Analysis

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Faculty Opinions recommendation of Facilitation at single synapses probed with optical quantal analysis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1007941.115457 ◽

2002 ◽

Author(s):

Erwin Neher

Keyword(s):

Quantal Analysis

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Faculty Opinions recommendation of Cannabinoid- and lysophosphatidylinositol-sensitive receptor GPR55 boosts neurotransmitter release at central synapses.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717992219.793473586 ◽

2013 ◽

Author(s):

Andreas Zimmer

Keyword(s):

Neurotransmitter Release ◽

Central Synapses

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AZP2006, a new promising treatment for Alzheimer’s and related diseases

Scientific Reports ◽

10.1038/s41598-021-94708-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

N. Callizot ◽

C. Estrella ◽

S. Burlet ◽

A. Henriques ◽

C. Brantis ◽

...

Keyword(s):

Therapeutic Application ◽

Neuroprotective Effects ◽

Beneficial Effects ◽

Potential Therapeutic Application ◽

Promising Treatment ◽

Central Synapses ◽

First Time ◽

Pgrn Level

AbstractProgranulin (PGRN) is a protein with multiple functions including the regulation of neuroinflammation, neuronal survival, neurite and synapsis growth. Although the mechanisms of action of PGRN are currently unknown, its potential therapeutic application in treating neurodegenerative diseases is huge. Thus, strategies to increase PGRN levels in patients could provide an effective treatment. In the present study, we investigated the effects of AZP2006, a lysotropic molecule now in phase 2a clinical trial in Progressive Supranuclear Palsy patients, for its ability to increase PGRN level and promote neuroprotection. We showed for the first time the in vitro and in vivo neuroprotective effects of AZP2006 in neurons injured with Aβ1–42 and in two different pathological animal models of Alzheimer’s disease (AD) and aging. Thus, the chronic treatment with AZP2006 was shown to reduce the loss of central synapses and neurons but also to dramatically decrease the massive neuroinflammation associated with the animal pathology. A deeper investigation showed that the beneficial effects of AZP2006 were associated with PGRN production. Also, AZP2006 binds to PSAP (the cofactor of PGRN) and inhibits TLR9 receptors normally responsible for proinflammation when activated. Altogether, these results showed the high potential of AZP2006 as a new putative treatment for AD and related diseases.

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