The goal of this project is to understand mechanisms of trans-synaptic communication during development and
plasticity of synapses. During the past many years, with support from this grant, we have pioneered work with
fundamental implications to our understanding of synaptic plasticity signals, demonstrating an essential role for Wnts
in these processes. The linkage between Wnts and severe neurological conditions, such as Alzheimer’s disease, and
schizophrenia1,2, makes our findings particularly impactful. During the past 5 years, the funding stability provided by
this MERIT award, enabled us to significantly expand our field of expertise, which resulted in several highly
significant and unexpected discoveries, which form the basis of the work proposed over the next 5 years of the award.
In particular, we documented a totally novel mode of intercellular communication, ViSyToR (Viral Synaptic Transfer
of RNA) a retroviral-like mechanism of trans-cellular mRNA transfer. In addition, we provided compelling evidence
that ViSyToR was used to carry mRNA encoding a master regulator of synaptic plasticity, Arc/Arg2.1. In the
proposed extension of this MERIT award we will (a) test the hypothesis that Copia retrotransposon forms have a
physiological role in trans-synaptic communication, (b) determine if other Gag-encoding genes and transposons
function in trans-synaptic communication using the ViSyToR pathway, and (c) unravel mechanisms of ViSyToR
function at synapses, including interactions between Wg and dArc1.