Title |
PKCα integrates spatiotemporally distinct Ca2+ and autocrine BDNF signaling to facilitate synaptic plasticity
|
---|---|
Published in |
Nature Neuroscience, July 2018
|
DOI | 10.1038/s41593-018-0184-3 |
Pubmed ID | |
Authors |
Lesley A Colgan, Mo Hu, Jaime A. Misler, Paula Parra-Bueno, Corey M. Moran, Michael Leitges, Ryohei Yasuda |
Abstract |
The protein kinase C (PKC) enzymes have long been established as critical for synaptic plasticity. However, it is unknown whether Ca2+-dependent PKC isozymes are activated in dendritic spines during plasticity and, if so, how this synaptic activity is encoded by PKC. Here, using newly developed, isozyme-specific sensors, we demonstrate that classical isozymes are activated to varying degrees and with distinct kinetics. PKCα is activated robustly and rapidly in stimulated spines and is the only isozyme required for structural plasticity. This specificity depends on a PDZ-binding motif present only in PKCα. The activation of PKCα during plasticity requires both NMDA receptor Ca2+ flux and autocrine brain-derived neurotrophic factor (BDNF)-TrkB signaling, two pathways that differ vastly in their spatiotemporal scales of signaling. Our results suggest that, by integrating these signals, PKCα combines a measure of recent, nearby synaptic plasticity with local synaptic input, enabling complex cellular computations such as heterosynaptic facilitation of plasticity necessary for efficient hippocampus-dependent learning. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 11 | 31% |
Italy | 2 | 6% |
France | 2 | 6% |
Australia | 1 | 3% |
Israel | 1 | 3% |
Brazil | 1 | 3% |
Sweden | 1 | 3% |
India | 1 | 3% |
Finland | 1 | 3% |
Other | 2 | 6% |
Unknown | 13 | 36% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 25 | 69% |
Scientists | 6 | 17% |
Science communicators (journalists, bloggers, editors) | 3 | 8% |
Practitioners (doctors, other healthcare professionals) | 2 | 6% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 200 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 45 | 23% |
Researcher | 32 | 16% |
Student > Master | 16 | 8% |
Student > Doctoral Student | 13 | 7% |
Professor | 13 | 7% |
Other | 40 | 20% |
Unknown | 41 | 21% |
Readers by discipline | Count | As % |
---|---|---|
Neuroscience | 77 | 39% |
Agricultural and Biological Sciences | 27 | 14% |
Biochemistry, Genetics and Molecular Biology | 23 | 12% |
Medicine and Dentistry | 9 | 5% |
Psychology | 3 | 2% |
Other | 14 | 7% |
Unknown | 47 | 24% |