Precise Temporal Regulation of Molecular Diffusion within Dendritic Spines by Actin Polymers during Structural Plasticity.

The biochemical transduction of excitatory synaptic signals occurs in the cytoplasm within dendritic spines. The associated reaction kinetics are shaped by the mobility of the signaling molecules; however, accurate monitoring of diffusional events within the femtoliter-sized spine structures has not yet been demonstrated. Here, we applied two-photon fluorescence correlation spectroscopy and raster image correlation spectroscopy to monitor protein dynamics within spines, revealing that F-actin restricts the mobility of proteins with a molecular mass of >100 kDa. This restriction is transiently removed during actin remodeling at the initial phase of spine structural plasticity. Photobleaching experiments combined with super-resolution imaging indicate that this increase in mobility facilitates molecular interactions, which may modulate the functions of key postsynaptic signaling molecules, such as Tiam1 and CaMKII. Thus, actin polymers in dendritic spines act as precise temporal regulators of molecular diffusion and modulate signal transduction during synaptic plasticity.

LIS1-dependent retrograde translocation of excitatory synapses in developing interneuron dendrites.

Synaptic remodelling coordinated with dendritic growth is essential for proper development of neural connections. After establishment of synaptic contacts, synaptic junctions are thought to become stationary and provide fixed anchoring points for further dendritic growth. However, the possibility of active translocation of synapses along dendritic protrusions, to guide the proper arrangement of synaptic distribution, has not yet been fully investigated. Here we show that immature dendrites of γ-aminobutyric acid-positive interneurons form long protrusions and that these protrusions serve as conduits for retrograde translocation of synaptic contacts to the parental dendrites. This translocation process is dependent on microtubules and the activity of LIS1, an essential regulator of dynein-mediated motility. Suppression of this retrograde translocation results in disorganized synaptic patterns on interneuron dendrites. Taken together, these findings suggest the existence of an active microtubule-dependent mechanism for synaptic translocation that helps in the establishment of proper synaptic distribution on dendrites.