IGF-1 Receptor Differentially Regulates Spontaneous and Evoked Transmission via Mitochondria at Hippocampal Synapses

2016 | journal article. A publication with affiliation to the University of Göttingen.

Jump to: Cite & Linked | Documents & Media | Details | Version history

Cite this publication

​IGF-1 Receptor Differentially Regulates Spontaneous and Evoked Transmission via Mitochondria at Hippocampal Synapses​
Gazit, N.; Vertkin, I.; Shapira, I.; Helm, M.; Slomowitz, E.; Sheiba, M. & Mor, Y. et al.​ (2016) 
Neuron89(3) pp. 583​-597​.​ DOI: https://doi.org/10.1016/j.neuron.2015.12.034 

Documents & Media

License

Published Version

Attribution-NonCommercial-NoDerivs 4.0 CC BY-NC-ND 4.0

Details

Authors
Gazit, Neta; Vertkin, Irena; Shapira, Ilana; Helm, Martin; Slomowitz, Edden; Sheiba, Maayan; Mor, Yael; Rizzoli, Silvio ; Slutsky, Inna
Abstract
The insulin-like growth factor-1 receptor (IGF-1R) signaling is a key regulator of lifespan, growth, and development. While reduced IGF-1R signaling delays aging and Alzheimer's disease progression, whether and how it regulates information processing at central synapses remains elusive. Here, we show that presynaptic IGF-1Rs are basally active, regulating synaptic vesicle release and short-term plasticity in excitatory hippocampal neurons. Acute IGF-1R blockade or transient knockdown suppresses spike-evoked synaptic transmission and presynaptic cytosolic Ca2+ transients, while promoting spontaneous transmission and resting Ca2+ level. This dual effect on transmitter release is mediated by mitochondria that attenuate Ca2+ buffering in the absence of spikes and decrease ATP production during spiking activity. We conclude that the mitochondria, activated by IGF-1R signaling, constitute a critical regulator of information processing in hippocampal neurons by maintaining evoked-to-spontaneous transmission ratio, while constraining synaptic facilitation at high frequencies. Excessive IGF-1R tone may contribute to hippocampal hyperactivity associated with Alzheimer's disease.
Issue Date
2016
Status
published
Publisher
Cell Press
Journal
Neuron 
ISSN
1097-4199; 0896-6273

Reference

Citations


Social Media