In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 28, No. 53 ( 2008-12-31), p. 14450-14458
Kurzfassung:
During development of the calyx of Held synapse, presynaptic action potentials (APs) become substantially faster and briefer. Nevertheless, this synapse is able to upregulate quantal output triggered by arriving APs. Briefer APs lead to less effective gating of voltage-gated Ca 2+ channels (VGCCs). Therefore, mechanisms downstream of Ca 2+ entry must effectively compensate for the attenuated Ca 2+ influx associated with shorter APs in more mature calyces. This compensation could be achieved by tighter spatial coupling between VGCCs and synaptic vesicles, so that the latter are exposed to higher intracellular Ca 2+ concentration ([Ca 2+ ] i ). Alternatively or additionally, the Ca 2+ sensitivity of the release apparatus may increase during synapse development. To differentiate between these possibilities, we combined paired patch-clamp recordings with Ca 2+ imaging and flash photolysis of caged Ca 2+ and estimated the [Ca 2+ ] i requirements for vesicle release in the developing mouse calyx of Held synapse. Surprisingly, the dose–response relationship between [Ca 2+ ] i and release rate was shifted slightly to the right in more mature calyces, rendering their vesicles slightly less sensitive to incoming Ca 2+ . Taking into account the time course and peak rates of AP-evoked release transients for the corresponding developmental stages, we estimate the local [Ca 2+ ] i “seen” by the Ca 2+ sensors on synaptic vesicles to increase from 35 to 56 μ m [from postnatal day 9 (P9)–P11 to P16–P19]. Our results reinforce the idea that developmental tightening of the spatial coupling between VGCCs and synaptic vesicles plays a predominant role in enhancing quantal output at this synapse and possibly other central synapses.
Materialart:
Online-Ressource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.4245-08.2008
Sprache:
Englisch
Verlag:
Society for Neuroscience
Publikationsdatum:
2008
ZDB Id:
1475274-8
SSG:
12
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