Large and Small Dendritic Spines Serve Different Interacting Functions in Hippocampal Synaptic Plasticity and Homeostasis

Abstract

The laying down of memory requires strong stimulation resulting in specific changes in synaptic strength and corresponding changes in size of dendritic spines. Strong stimuli can also be pathological, causing a homeostatic response, depressing and shrinking the synapse to prevent damage from too much Ca2+ influx. But do all types of dendritic spines serve both of these apparently opposite functions? Using confocal microscopy in organotypic slices from mice expressing green fluorescent protein in hippocampal neurones, the size of individual spines along sections of dendrite has been tracked in response to application of tetraethylammonium. This strong stimulus would be expected to cause both a protective homeostatic response and long-term potentiation. We report separation of these functions, with spines of different sizes reacting differently to the same strong stimulus. The immediate shrinkage of large spines suggests a homeostatic protective response during the period of potential danger. In CA1, long-lasting growth of small spines subsequently occurs consolidating long-term potentiation but only after the large spines return to their original size. In contrast, small spines do not change in dentate gyrus where potentiation does not occur. The separation in time of these changes allows clear functional differentiation of spines of different sizes.

Dendritic spine geometry and spine apparatus organization govern the spatiotemporal dynamics of calcium

“…We note that in our model, we assume constant pump density, which highlights the volume-to-surface area ratios between various shapes ( Matsuzaki et al, 2001 ; Noguchi et al, 2005 ). Experimental results have already shown different behavior in large versus small dendritic spines ( Paulin et al, 2016 ), and additional studies on dendritic spine geometry have shown that stable, mature spines are usually larger spines that tend toward mushroom shapes as they grow around adjoining axons and are more likely to have a SpApp ( Spacek and Harris, 1997 ). In comparison, younger, less stable spines tend to be smaller and more spherical ( Spacek and Harris, 1997 ; Berry and Nedivi, 2017 ).…”

“…1 c for the different model geometries used in this study. These geometries were inspired by reconstructions ( Bartol et al, 2015a ; Griffith et al, 2016 ; Paulin et al, 2016 ) and were idealized for ease of computation. For the variations of the base of the neck, we also include a condition with an explicit dendrite modeled as a cylinder attached to the spine neck, Figs.…”

DLITE Uses Cell-Cell Interface Movement to Better Infer Cell-Cell Tensions

“…The need for dynamic force-inference tools to understand cell shape and colony rearrangement is driven by their applicability to morphogenic processes from wound healing to germ-band extension to colony reorganization ( 1 , 2 , 3 , 4 ). These processes rely on transient mechanical forces that are ideally detected by the extended nonperturbing observations for which DLITE is designed.…”

“…Cell shape, forces, and function are closely related ( 1 , 2 , 3 , 4 ). Cell shape is known to affect intracellular organization and transmission of cytoskeletal forces ( 5 , 6 , 7 ).…”

Structural and functional plasticity of dendritic spines – root or result of behavior?

“…Synaptic strengthening and long-term potentiation (LTP) are associated with increases in spine density and/or spine head diameter, while synaptic weakening induced by long-term depression (LTD) causes spine retraction (Alvarez and Sabatini 2007;De Roo et al 2008a;Sala and Segal 2014;Segal 2005; van der Zee 2015). However, it should be noted that synaptic overstimulation can also lead to spine shrinkage to prevent damage from excess calcium influx (Paulin et al 2016).…”