Modulation of Presynaptic Release Probability by the Vertebrate-Specific Protein Mover

• DOI: 10.1016/j.neuron.2015.07.001
• Publication Date: 2015-07-23T11:46:31Z
• Authors: Christoph Körber; Heinz Horstmann; Varun Venkataramani; Frank Herrmannsdö...; Thomas Kremer; Michaela Kaiser; Darius B. Schwenger; Saheeb Ahmed; Camin Dean; Thomas Dresbach; Thomas Kuner
• Keywords: 0301 basic medicine; Neuroscience(all); Presynaptic Terminals; Excitatory Postsynaptic Potentials; Nerve Tissue Proteins; Rats; Rats, Sprague-Dawley; 03 medical and health sciences; Organ Culture Techniques; Gene Knockdown Techniques; Animals; Brain Stem; Probability

Mover, a member of the exquisitely small group of vertebrate-specific presynaptic proteins, has been discovered as an interaction partner of the scaffolding protein Bassoon, yet its function has not been elucidated. We used adeno-associated virus (AAV)-mediated shRNA expression to knock down Mover in the calyx of Held in vivo. Although spontaneous synaptic transmission remained unaffected, we found a strong increase of the evoked EPSC amplitude. The size of the readily releasable pool was unaltered, but short-term depression was accelerated and enhanced, consistent with an increase in release probability after Mover knockdown. This increase in release probability was not caused by alterations in Ca(2+) influx but rather by a higher Ca(2+) sensitivity of the release machinery, as demonstrated by presynaptic Ca(2+) uncaging. We therefore conclude that Mover expression in certain subsets of synapses negatively regulates synaptic release probability, constituting a novel mechanism to tune synaptic transmission.