Subunit exchange enhances information retention by CaMKII in dendritic spines
| Autor: | Singh, Dilawar, Bhalla, Upinder Singh |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Dendritic spine Long-Term Potentiation Hippocampus Synaptic Transmission memory maintenance Synapse Phosphorylation Biology (General) CaMKII Chemistry musculoskeletal neural and ocular physiology General Neuroscience General Medicine musculoskeletal system cardiovascular system Medicine Research Article Computational and Systems Biology QH301-705.5 Dendritic Spines Science Protein subunit Models Neurological Phosphatase General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Memory Ca2+/calmodulin-dependent protein kinase None Humans Computer Simulation General Immunology and Microbiology Protein turnover Post-Synaptic Density Protein phosphatase 1 bistable Receptors Neuropeptide Y Protein Subunits Cytosol 030104 developmental biology Gene Expression Regulation nervous system Synaptic plasticity Biophysics Calcium-Calmodulin-Dependent Protein Kinase Type 2 Postsynaptic density Neuroscience |
| Zdroj: | eLife, Vol 7 (2018) eLife |
| ISSN: | 2050-084X |
| DOI: | 10.7554/elife.41412 |
| Popis: | Molecular bistables are strong candidates for long-term information storage, for example, in synaptic plasticity. Calcium/calmodulin-dependent protein Kinase II (CaMKII) is a highly expressed synaptic protein which has been proposed to form a molecular bistable switch capable of maintaining its state for years despite protein turnover and stochastic noise. It has recently been shown that CaMKII holoenzymes exchange subunits among themselves. Here, we used computational methods to analyze the effect of subunit exchange on the CaMKII pathway in the presence of diffusion in two different micro-environments, the post synaptic density (PSD) and spine cytosol. We show that CaMKII exhibits multiple timescales of activity due to subunit exchange. Further, subunit exchange enhances information retention by CaMKII both by improving the stability of its switching in the PSD, and by slowing the decay of its activity in the spine cytosol. The existence of diverse timescales in the synapse has important theoretical implications for memory storage in networks. eLife digest The brain stores memories by changing the strength of synapses, the connections between neurons. Synapses that change their strength easily can quickly encode new information. But such synapses are also unstable. They tend to revert back to their original state and so struggle to retain information. By contrast, synapses that are slow to change their strength are slow to learn, but are good at remembering. The difference is a little like that between writing a message in wet sand versus carving it into stone. It is quick and easy to write on sand, but the resulting marks are temporary. Writing on stone is slow and difficult, but the results last far longer. The brain must strike a balance between how fast synapses can learn and how well they can retain that information. One molecule that helps with this is a synaptic protein called CaMKII. Each CaMKII molecule consists of multiple subunits and exists in either an active or inactive state. Experiments have shown that CaMKII molecules can swap subunits. But how does this affect memory? Singh and Bhalla used a computer model to simulate subunit exchange between CaMKII molecules. The results revealed that when active CaMKII molecules swap subunits, synapses become better at retaining information. However, when inactive CaMKII molecules swap subunits, synapses do not become better at encoding information. Subunit exchange by CaMKII thus helps synapses stabilize existing memories, rather than form new ones. This makes it easier for the brain to retain stored information despite threats to stability such as the turnover of proteins. A better knowledge of how the brain balances quick learning and slow forgetting may help us to better understand brain disorders, such as Alzheimer’s disease (in which patients struggle to remember), and post-traumatic stress disorder (in which patients struggle to forget). Biological memory networks can also inspire artificial memory systems. Damaging a few components of a computer memory can erase all the stored information. By contrast, the brain loses many neurons every day without suffering the same catastrophic failure. Mimicking such fault tolerance in an artificial system would be highly valuable for storing critical memories. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|