Homeostasis of dendritic spines in hippocampal CA1 cells.
Doctoral thesis, UCL (University College London).
Synaptic connections in the brain respond throughout their lives to the activity of incoming neurones, adjusting their biological properties to increment activity-dependent changes but also avoid run-away excitation or complete loss of transmission. To ensure synapses remain functional when inputs change over time, compensatory mechanisms, coined homeostatic plasticity, take place either globally or locally. The correlation between synaptic strength and dendritic spine size has been clearly established, and thus imaging dendritic spines under various activity conditions has become accepted as a valid way of studying homeostatic changes of postsynaptic strength. Many neurological diseases demonstrate abnormalities of dendritic spines, directly linking their properties to the efficient functioning of the network. Understanding how dendritic spines are regulated under global changes of network activity is important to unveil clues about how to tackle those deficits in disease. Studying morphology of dendritic spines requires intensive and careful analysis, and a substantial part of this work has been dedicated to finding an appropriate way to analyse the data. Dendritic spines showed a remarkably stable density in CA1 pyramidal neurones during the second week in vitro, when treatments altering plasticity or even deafferentation failed to modify the autonomous development. However, deafferentation carried out a week later decreased the overall spine density and increased spine head size, specifically in the area that normally receives inputs from the transected axons. The strong activity of the Schaffer collateral axons in organotypic slices results in enlarged spines in the apical compared with basal dendrites. This difference between pathways was abolished by inhibition of CaMKII. Activity-dependent and homeostatic plasticities are working intricately to maintain the network efficacy. They operate at a local level in an age-dependent manner and are differentially modulated by the CaMKII or PKA pathways.
|Title:||Homeostasis of dendritic spines in hippocampal CA1 cells|
|Open access status:||An open access version is available from UCL Discovery|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Neuroscience, Physiology and Pharmacology|
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