| First Author | Gazit N | Year | 2016 |
| Journal | Neuron | Volume | 89 |
| Issue | 3 | Pages | 583-97 |
| PubMed ID | 26804996 | Mgi Jnum | J:230868 |
| Mgi Id | MGI:5766399 | Doi | 10.1016/j.neuron.2015.12.034 |
| Citation | Gazit N, et al. (2016) IGF-1 Receptor Differentially Regulates Spontaneous and Evoked Transmission via Mitochondria at Hippocampal Synapses. Neuron 89(3):583-97 |
| abstractText | 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 Ca(2+) transients, while promoting spontaneous transmission and resting Ca(2+) level. This dual effect on transmitter release is mediated by mitochondria that attenuate Ca(2+) 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. VIDEO ABSTRACT. |
