Activin increases the number of synaptic contacts and the length of dendritic spine necks by modulating spinal actin dynamics

Abstract

Long-lasting modifications in synaptic transmission depend on de novo gene expression in neurons. The expression of activin, a member of the transforming growth factor β (TGF-β) superfamily, is upregulated during hippocampal long-term potentiation (LTP). Here, we show that activin increased the average number of presynaptic contacts on dendritic spines by increasing the population of spines that were contacted by multiple presynaptic terminals in cultured neurons. Activin also induced spine lengthening, primarily by elongating the neck, resulting in longer mushroom-shaped spines. The number of spines and spine head size were not significantly affected by activin treatment. The effects of activin on spinal filamentous actin (F-actin) morphology were independent of protein and RNA synthesis. Inhibition of cytoskeletal actin dynamics or of the mitogen-activated protein (MAP) kinase pathway blocked not only the activin-induced increase in the number of terminals contacting a spine but also the activin-induced lengthening of spines. These results strongly suggest that activin increases the number of synaptic contacts by modulating actin dynamics in spines, a process that might contribute to the establishment of late-phase LTP.

Canonical TGF-β Signaling Is Required for the Balance of Excitatory/Inhibitory Transmission within the Hippocampus and Prepulse Inhibition of Acoustic Startle

“…Inactivation of activin receptor in the forebrain enhanced both GABA A and GABA B currents, but whether this requires canonical signaling was not tested. In contrast, in cultured hippocampal neurons, addition of activin results in spine contact and NMDA receptor changes through protein synthesis-independent (noncanonical) phosphorylation of actin filaments and postsynaptic scaffold proteins (Shoji-Kasai et al, 2007;Kurisaki et al, 2008). Our results suggest that Smad4 regulates GABA A transmission; however, since Smad4 represents a point of convergence between TGF-␤/activin and BMP signaling pathways, it is not clear which set of ligands might be involved in this response.…”

Involvement of the Serum Response Factor Coactivator Megakaryoblastic Leukemia (MKL) in the Activin-regulated Dendritic Complexity of Rat Cortical Neurons*

“…S9). In relation to dendritic spine morphology, activin increases the spine length of hippocampal neurons in a protein and RNA synthesis-independent manner (36). Therefore, our observation that activin promotes dendritic complexity may represent a late phase phenomenon that occurs after an increase in the number or strength of synaptic contacts that are made during the early phase of response to activin.…”

Interfering with the Actin Network and Its Effect on Long-Term Potentiation and Synaptic Tagging in Hippocampal CA1 Neurons in SlicesIn Vitro

“…Thus, it is feasible that the actin network guarantees the molecular/morphological basis for a tag-related housekeeping process, on top of which other key molecules like CaMKII or MAPK are only able to exert their action in synapses specifically marked either for LTP or LTD processes. Furthermore, the actin network could be involved in the PRP capture process itself by providing a distinct geometry for interactions of the kinases with the PRPs such as sculpting active synaptic zones or the whole synaptic spine, guaranteeing, for example, the activation or transport of PRPs into the spine or the transport of new AMPA-receptors to maintain LTP (Fukazawa et al, 2003;Lisman, 2003;Chen et al, 2007;Shoji-Kasai et al, 2007;Yang et al, 2008;Peng et al, 2009). Alternatively, actin filament formation could also be locally involved in PRP synthesis.…”