CAPS1 stabilizes the state of readily releasable synaptic vesicles to fusion competence at CA3-CA1 synapses in adult hippocampus.

Yo Shinoda,Yugo Fukazawa,Yuki Ishii,Teiichi Furuichi,Shigeyoshi Itohara,Takuji Iwasato,Yoshitake Sano,Chiaki Ishii,Tetsushi Sadakata

doi:10.1038/srep31540

Abstract

Calcium-dependent activator protein for secretion 1 (CAPS1) regulates exocytosis of dense-core vesicles in neuroendocrine cells and of synaptic vesicles in neurons. However, the synaptic function of CAPS1 in the mature brain is unclear because Caps1 knockout (KO) results in neonatal death. Here, using forebrain-specific Caps1 conditional KO (cKO) mice, we demonstrate, for the first time, a critical role of CAPS1 in adult synapses. The amplitude of synaptic transmission at CA3–CA1 synapses was strongly reduced, and paired-pulse facilitation was significantly increased, in acute hippocampal slices from cKO mice compared with control mice, suggesting a perturbation in presynaptic function. Morphological analysis revealed an accumulation of synaptic vesicles in the presynapse without any overall morphological change. Interestingly, however, the percentage of docked vesicles was markedly decreased in the Caps1 cKO. Taken together, our findings suggest that CAPS1 stabilizes the state of readily releasable synaptic vesicles, thereby enhancing neurotransmitter release at hippocampal synapses.

Highlights

On the plasma membrane) binds[23,24,25]
In the present study, using forebrain-specific Caps[1] conditional KO (cKO) mice and acute Caps[1] deletion in primary neurons, we demonstrate that CAPS1 is required for the proper exocytosis of synaptic vesicles (SVs) at CA3–CA1 synapses in the adult hippocampus
A previous study showed a reduction in EPSC amplitude in primary hippocampal microisland cultures prepared from Caps1/2 double KO (DKO) mice[18]

Summary

Introduction

On the plasma membrane) binds[23,24,25]. The interaction of CAPS1 and/or Munc[] with syntaxin-1 has been suggested to induce fusion competence (priming) of DCVs10,12,21,26 and SVs12,18. There are studies using in vitro microisland cultures and organotypic cultures from E18–P0 Caps[1] KO mouse pups[18,27], it remains unclear whether CAPS1 regulates SV release in the adult brain because Caps[1] KO mice die soon after birth. Our results show that CAPS1 deficiency decreases activity-dependent SV release events in vivo at CA3–CA1 synapses in adult hippocampal slices. It causes the accumulation of SVs near the active zone but reduces the number of SVs at the plasma membrane of presynaptic terminals. Our results for the first time indicate that CAPS1 stabilizes the state of readily-releasable SVs at mature synapses in the adult hippocampus

Methods

Results

Conclusion