Shapeshifting for memory: Biochemical and electrical signaling in dendritic spines

One of the biggest remaining mysteries of science is inside our heads: how does nature wire up a high-performance computer without having a detailed blueprint specifying the location and strength of every connection? It is assumed that local connectivity in our cortex is at first random, and during development undergoes refinement until only the ‘right' connections are left over. But how can the brain tell ‘right' from ‘wrong' connections? The majority of excitatory connections are formed on dendritic spines, tiny excrescences that cover almost the entire dendritic surface of most neurons. Since their discovery by Ramón y Cajal in 1896, neuroscientists have been fascinated by these structures, which ultimately determine which neurons in the brain become connected and form functional networks. Here we review the many important functions of spines and explain why electrical and biochemical processes in these tiny structures are thought to be crucial for the plasticity of the brai

Myosin V regulates synaptopodin clustering and localization in the dendrites of hippocampal neurons

The spine apparatus (SA) is an endoplasmic reticulum-related organelle that is present in a subset of dendritic spines in cortical and pyramidal neurons, and plays an important role in Ca2+ homeostasis and dendritic spine plasticity. The protein synaptopodin is essential for the formation of the SA and is widely used as a maker for this organelle. However, it is still unclear which factors contribute to its localization at selected synapses, and how it triggers local SA formation. In this study, we characterized development, localization and mobility of synaptopodin clusters in hippocampal primary neurons, as well as the molecular dynamics within these clusters. Interestingly, synaptopodin at the shaftassociated clusters is less dynamic than at spinous clusters. We identify the actin-based motor proteins myosin V (herein referring to both the myosin Va and Vb forms) and VI as novel interaction partners of synaptopodin, and demonstrate that myosin V is important for the formation and/or maintenance of the SA. We found no evidence of active microtubule-based transport of synaptopodin. Instead, new clusters emerge inside spines, which we interpret as the SA being assembled on-site