AbstractsBiology & Animal Science

Synaptic plasticity is a core feature of neuronal communication. It describes the activity- dependent change of the strength of synaptic transmission. Dependent on the duration of the transmission alteration synaptic plasticity is commonly divided into short-term and long-term plasticity. Whereas long-term plasticity is based on molecular changes at the presynaptic and/or postsynaptic site, factors influencing short-term plasticity are predominantly located at the presynapse. There, basic synaptic transmission and activity-dependent plasticity are governed at the active zone. This is a presynaptic plasma membrane patch with a complex protein network where vesicles are docked and primed, meaning that the required release machinery is assembled together with the vesicle and voltage-dependent Ca2+-channels. This protein network ensures the spatiotemporally highly regulated process of action potential triggered Ca2+-influx and the subsequent exocytosis of neurotransmitter filled vesicles. In this work we focused on the presynaptic protein RIM1alpha, a core component of the multiprotein complex at the active zone. Dependent on the type of synapse tested, previous studies have shown RIM1alpha to either alter short-term plasticity or to be an essential mediator of presynaptic long-term plasticity or both. Combining electrophysiological analysis of release properties and synaptic plasticity with two- photon calcium imaging at the cerebellar granule cell synapse we could show that the loss of the single isoform RIM1alpha already leads to a significant reduction in action potential triggered Ca2+- influx at axonal boutons. As a consequence the release probability is reduced and short-term plasticity is enhanced. In contrast we could not find any difference in the expression of presynaptic long-term plasticity. To further test this finding, we mimicked the reduction of Ca2+- influx found in RIM1alpha KO mice by reducing the external Ca2+-concentration. The resulting lower intracellular Ca2+-concentration does not fall below but comes close to the threshold of inducibility of long-term plasticity. Our results argue against an indispensable role of RIM1alpha in the expression of long-term plasticity but indicate a rather universal role of the protein in interacting with voltage-dependent Ca2+-channels to enable proper synaptic neurotransmitter release. In addition, we found a significant difference between the Ca2+-influx in boutons of the ascending compared to the parallel fiber segment of granule cell axons, which adds additional information to previous studies that showed differential synaptic properties of these two axonal segments as well. Synaptische Plastizität beschreibt die aktivitätsabhängige Änderung der Stärke synaptischer Transmission und stellt ein Hauptmerkmal neuronaler Kommunikation dar. Abhängig von der Dauer der Transmissionsänderungen wird sie in Kurzzeit- und Langzeitplastizität unterteilt. Während Langzeitplastizität auf molekularen Änderungen der prä- und/oder postsynaptischen Seite basiert, sind die…