TY  - GEN
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/12108/
A1  - Körber, Christoph
N2  - Signal transduction at chemical synapses in the central nervous system relies on the tightly regulated release of neurotransmitter from the active zone of the presynaptic compartment. Although key components of the machinery responsible for transport, docking, priming and fusion of synaptic vesicles have been identified, our understanding of the regulation of this complex process is still incomplete. This is especially true for the probability of release, which determines whether or not one or more synaptic vesicles get released upon arrival of an action potential at the active zone. Albeit the probabilistic nature of neurotransmitter release is one of the key features underlying higher order brain functions such as learning and memory, the mechanisms that regulate this process remain largely elusive. In the present study, we examined the functional properties of the recently identified presynaptic vertebrate-specific protein Mover. Therefore, we generated an in vivo knock-down of Mover using adeno-associated virus mediated shRNA expression in the globular bushy cells of the ventral cochlear nucleus, the projection neurons forming the calyx of Held. 3D immunohistochemistry 10 days after virus injection at postnatal day 2, revealed a strong reduction of Mover expression in identified single calyces expressing mOrange in cis with the shRNA. Electrophysiological characterization of Mover knock-down synapses at postnatal days 12 and 13 revealed increased EPSC amplitudes, increased and accelerated short-term depression and increased recovery from depression as compared to controls. Contrarily, spontaneous release properties, EPSC kinetics, readily-releasable pool size and synaptic vesicle mobilization were not affected by Mover knock-down. These findings are in line with an increased probability of release after Mover knock-down. The increase in release probability was confirmed by presynaptic capacitance recordings in which near-maximal release in Mover knock-down calyces was achieved with shorter depolarization steps as compared to controls. Presynaptic calcium currents were not affected by Mover, assuring that the increase in release probability was not due to alterations in calcium influx. Thus, we examined the calcium sensitivity of release in Mover knock-down synapses by monitoring the EPSC amplitude in different extracellular calcium concentrations. In these experiments, we found EPSC amplitudes in 1.5 mM extracellular calcium significantly increased upon knock-down of Mover suggesting that Mover indeed decreased the calcium sensitivity of release. In summary, our findings show that Mover acts as a negative regulator of release probability, most likely by reducing the calcium sensitivity of release. Taking the previously shown expression pattern of Mover in certain subsets of synapses into account, Mover may constitute a novel mechanism to tune synaptic transmission. 
ID  - heidok12108
Y1  - 2011///
TI  - Functional characterization of the vertebrate-specific presynaptic protein Mover in the calyx of Held
AV  - public
KW  - Held'scher Calyx 
KW  -  Neurotransmitterfreisetzung 
KW  -  präsynaptischsynaptic transmission 
KW  -  calyx of Held 
KW  -  synaptic release 
KW  -  presynaptic
ER  -