Loss of 4E-BP converts cerebellar long-term depression to long-term potentiation.

Genetic perturbances in translational regulation result in defects in cerebellar motor learning; however, little is known about the role of translational mechanisms in the regulation of cerebellar plasticity. We show that genetic removal of 4E-BP, a translational suppressor and target of mammalian target of rapamycin complex 1, results in a striking change in cerebellar synaptic plasticity. We find that cerebellar long-term depression (LTD) at parallel fiber-Purkinje cell synapses is converted to long-term potentiation in 4E-BP knockout mice.

TIE: A Method to Electroporate Long DNA Templates into Preimplantation Embryos for CRISPR-Cas9 Gene Editing.

Precise genome editing using CRISPR typically requires delivery of guide RNAs, Cas9 endonuclease, and DNA repair templates. Both microinjection and electroporation effectively deliver these components into mouse zygotes provided the DNA template is an oligonucleotide of only a few hundred base pairs. However, electroporation completely fails with longer double-stranded DNAs leaving microinjection as the only delivery option.

Removing 4E-BP Enables Synapses to Refine without Postsynaptic Activity.

Throughout the developing nervous system, considerable synaptic re-organization takes place as postsynaptic neurons extend dendrites and incoming axons refine their synapses, strengthening some and eliminating others. It is well accepted that these processes rely on synaptic activity; however, the mechanisms that lead to this developmental reorganization are not fully understood. Here, we explore the regulation of cap-dependent translation, a mechanism known to play a role in synaptic growth and plasticity.