Barriers in the brain: resolving dendritic spine morphology and compartmentalization

Abstract

Dendritic spines are micron-sized protrusions that harbor the majority of excitatory synapses in the central nervous system. The head of the spine is connected to the dendritic shaft by a 50-400 nm thin membrane tube, called the spine neck, which has been hypothesized to confine biochemical and electric signals within the spine compartment. Such compartmentalization could minimize interspinal crosstalk and thereby support spine-specific synapse plasticity. However, to what extent compartmentalization is governed by spine morphology, and in particular the diameter of the spine neck, has remained unresolved. Here, we review recent advances in tool development - both experimental and theoretical - that facilitate studying the role of the spine neck in compartmentalization. Special emphasis is given to recent advances in microscopy methods and quantitative modeling applications as we discuss compartmentalization of biochemical signals, membrane receptors and electrical signals in spines. Multidisciplinary approaches should help to answer how dendritic spine architecture affects the cellular and molecular processes required for synapse maintenance and modulation.

Keywords: compartment; dendritic spine; diffusion; modeling; super-resolution microscopy.

Figure 1

Diffusion models for signaling molecules in spines. The spread of active signaling molecules (green) with long activity life-times depends on their diffusion rate. Limiting the activity life time of signaling molecules is an orthogonal approach to confine signaling activity to individual spines.

Figure 2

Correlation of spine morphology and diffusional coupling. (A) Left: Two dendritic spines filled with soluble fluorophores were imaged with STED microscopy and neck diameters measured with line scans. Scale bar 500 nm. Right: The rate of diffusional coupling (τ) of these spines was measured by the recovery of photobleaced fluorophores (FRAP). (B) τ plotted as function of neck width. Gray line indicates inverse-square fit with 95% confidence interval in pink. Reprinted by permission from Macmillan Publishers Ltd: Nature Neuroscience (Tønnesen et al., 2014), copyright 2014.

Figure 3

The dendritic spine as a regulatory system. (A) Schematic view of a dendritic spine containing recycling endosomes, glutamate receptors and actin cytoskeleton. (B) Decreasing the radius of the neck increases the retention of receptors at the synapse, indicated by the time-evolution of the density at the synapse (dashed area) for a planar, stubby and mushroom shaped spine (Kusters et al., 2013). (C) Phase diagram indicating that decreasing the neck radius increases the force necessary to transport recycling endosomes through the actin rich constriction. (D) Typical sequence of shapes during the translocation of an endosome through the neck, obtained with three-dimensional Lattice-Boltzmann simulations (Kusters et al., 2014b).