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.
You may also like
Insulin-like hormones critical for brain plasticity
August 7, 2023Max Planck Florida Institute for Neuroscience
A Butterfly Effect
July 27, 2023Max Planck Florida Institute for Neuroscience
Deep learning models to study sentence comprehension...
June 28, 2023Max Planck Institute for Psycholinguistics
How the brain slows down when we focus our gaze
June 28, 2023Max Planck Institute for Biological Cybernetics
Fruit fly’s complex symphony of vision
June 6, 2023Max Planck Institute for Biological Intelligence
How tasty is the food? Ask your brain!
June 6, 2023Max Planck Institute for Biological Intelligence