Endogenous Rho-Kinase Signaling Maintains Synaptic Strength by Stabilizing the Size of the Readily Releasable Pool of Synaptic Vesicles

Paired-pulse depression (PPD) is a form of short-term plasticity that plays a central role in processing of synaptic activity and is manifest as a decrease in the size of the response to the second of two closely timed stimuli. Despite mounting evidence to the contrary, PPD is still commonly thought to reflect depletion of the pool of synaptic vesicles available for release in response to the second stimulus. Here it is shown that PPD cannot be accounted for by depletion at excitatory synapses made by hippocampal neurons because PPD is unaffected by changes in the fraction of the readily releasable pool (RRP) released by the first of a pair of pulses.

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The readily releasable pool of synaptic vesicles

Current Opinion in Neurobiology ◽

10.1016/j.conb.2016.12.012 ◽

2017 ◽

Vol 43 ◽

pp. 63-70 ◽

Cited By ~ 63

Author(s):

Pascal S Kaeser ◽

Wade G Regehr

Keyword(s):

Synaptic Vesicles ◽

Releasable Pool ◽

Readily Releasable Pool

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β-Adrenergic Receptors/Epac Signaling Increases the Size of the Readily Releasable Pool of Synaptic Vesicles Required for Parallel Fiber LTP

Journal of Neuroscience ◽

10.1523/jneurosci.0716-20.2020 ◽

2020 ◽

Vol 40 (45) ◽

pp. 8604-8617

Author(s):

Ricardo Martín ◽

Nuria García-Font ◽

Alberto Samuel Suárez-Pinilla ◽

David Bartolomé-Martín ◽

José Javier Ferrero ◽

...

Keyword(s):

Synaptic Vesicles ◽

Adrenergic Receptors ◽

Parallel Fiber ◽

Releasable Pool ◽

Readily Releasable Pool ◽

Β Adrenergic Receptors ◽

Epac Signaling

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Determinants of synaptic strength vary across an axon arbor

Journal of Neurophysiology ◽

10.1152/jn.00615.2011 ◽

2012 ◽

Vol 107 (9) ◽

pp. 2430-2441 ◽

Cited By ~ 6

Author(s):

Xiaoyu Peng ◽

Thomas D. Parsons ◽

Rita J. Balice-Gordon

Keyword(s):

Synaptic Vesicles ◽

Hippocampal Neurons ◽

Synaptic Strength ◽

Pool Size ◽

Spatial Modulation ◽

Readily Releasable Pool ◽

Single Axon ◽

Individual Vesicle ◽

Highly Correlated ◽

Vesicle Pool

We used synaptophysin-pHluorin expressed in hippocampal neurons to address how functional properties of terminals, namely, evoked release, total vesicle pool size, and release fraction, vary spatially across individual axon arbors. Consistent with previous reports, over short arbor distances (∼100 μm), evoked release was spatially heterogeneous when terminals contacted different postsynaptic dendrites or neurons. Regardless of the postsynaptic configuration, the evoked release and total vesicle pool size spatially covaried, suggesting that the fraction of synaptic vesicles available for release (release fraction) was similar over short distances. Evoked release and total vesicle pool size were highly correlated with the amount of NMDA receptors and PSD-95 in postsynaptic specialization. However, when individual axons were followed over longer distances (several hundred micrometers), a significant increase in evoked release was observed distally that was associated with an increased release fraction in distal terminals. The increase in distal release fraction can be accounted for by changes in individual vesicle release probability as well as readily releasable pool size. Our results suggest that for a single axon arbor, presynaptic strength indicated by evoked release over short distances is correlated with heterogeneity in total vesicle pool size, whereas over longer distances presynaptic strength is correlated with the spatial modulation of release fraction. Thus the mechanisms that determine synaptic strength differ depending on spatial scale.

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The Bruchpilot cytomatrix determines the size of the readily releasable pool of synaptic vesicles

The Journal of Cell Biology ◽

10.1083/jcb.201301072 ◽

2013 ◽

Vol 202 (4) ◽

pp. 667-683 ◽

Cited By ~ 65

Author(s):

Tanja Matkovic ◽

Matthias Siebert ◽

Elena Knoche ◽

Harald Depner ◽

Sara Mertel ◽

...

Keyword(s):

Synaptic Vesicles ◽

Circular Array ◽

Membrane Domain ◽

Releasable Pool ◽

Readily Releasable Pool ◽

Family Protein ◽

Biochemical Identification ◽

Macromolecular Architecture ◽

Bar Formation ◽

Ca2 Channels

Synaptic vesicles (SVs) fuse at a specialized membrane domain called the active zone (AZ), covered by a conserved cytomatrix. How exactly cytomatrix components intersect with SV release remains insufficiently understood. We showed previously that loss of the Drosophila melanogaster ELKS family protein Bruchpilot (BRP) eliminates the cytomatrix (T bar) and declusters Ca2+ channels. In this paper, we explored additional functions of the cytomatrix, starting with the biochemical identification of two BRP isoforms. Both isoforms alternated in a circular array and were important for proper T-bar formation. Basal transmission was decreased in isoform-specific mutants, which we attributed to a reduction in the size of the readily releasable pool (RRP) of SVs. We also found a corresponding reduction in the number of SVs docked close to the remaining cytomatrix. We propose that the macromolecular architecture created by the alternating pattern of the BRP isoforms determines the number of Ca2+ channel-coupled SV release slots available per AZ and thereby sets the size of the RRP.

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