signaling; auditory system; Drosophila; knockout mice; plasticity; synapse formation; precerebellar system; trans-synaptic signaling
Vickers Evan, Osypenko Denys, Clark Christopher, Okur Zeynep, Scheiffele Peter, Schneggenburger Ralf (2020), LTP of inhibition at PV interneuron output synapses requires developmental BMP signaling, in
Scientific Reports, 10(1), 10047-10047.
Vickers Evan D., Clark Christopher, Osypenko Denys, Fratzl Alex, Kochubey Olexiy, Bettler Bernhard, Schneggenburger Ralf (2018), Parvalbumin-Interneuron Output Synapses Show Spike-Timing-Dependent Plasticity that Contributes to Auditory Map Remodeling, in
Neuron, 1-16.
Xiao Le, Scheiffele Peter (2018), Local and long-range circuit elements for cerebellar function, in
Current Opinion in Neurobiology, 48, 146-152.
Kronander Elin, Michalski Nicolas, Lebrand Cécile, Hornung Jean-Pierre, Schneggenburger Ralf (2017), An organotypic slice culture to study the formation of calyx of Held synapses in-vitro, in
PLOS ONE, 12(4), e0175964-e0175964.
The connectivity and plasticity of neuronal networks underlies movement and more complex behaviors in all animals, including humans. The overarching goal of this project is to understanding the interface between molecular mechanisms and experience-dependent plasticity that shape the specificity and function of synaptic connections in the nervous system. Many examples for functional and structural plasticity have been described in previous studies. However, there is a paucity of knowledge about the molecular and cell biological mechanisms that instruct such plasticity processes. A theme that recently emerged in molecular neuroscience is the “re-use” of neuronal patterning signals (that instruct early development) in later stages of neuronal development. Bone morphogenetic proteins (BMPs) represent one such example. Well-known for their roles in neural induction and patterning BMPs have novel, unexpected roles in synapse development. In this joint project, we will use a combination of genetic, cell biological, imaging, and electrophysiological approaches to test the hypothesis that BMP signaling controls structural and functional plasticity in the developing and mature nervous system. To this end, we will apply complementary expertise in the analysis of synaptic connectivity and function to address the following common goals: Common Goal 1: Probe cellular logic and directionality of synaptic BMP signalingThe first synaptic signaling function of BMPs identified was a retrograde, trans-synaptic signal at the Drosophila neuromuscular junction. However, for most systems and synapses the directionality and function of synaptic BMP signaling are unknown. Using genetic approaches to target specific neuronal cell populations we will dissect the directionality of BMP signaling in several neuronal systems. These efforts should enable us to identify fundamental principles of BMP signaling in synapse specification and synaptic plasticity.Common Goal 2: Identify molecular effectors of synaptic BMP signaling One primary read-out of BMP-signaling is the modification of transcriptional programs. Despite the central importance of such programs only a very small number of transcriptional targets for synaptic BMP signaling have been identified. We will employ a novel, cell type-specific chromatin-immunoprecipitation approach to identify novel transcriptional targets in pre- and postsynaptic cell populations. Function of such targets in synapse formation and synaptic plasticity will then be examined in loss-of-function studies. In addition to the canonical nuclear signaling functions of the BMP-pathway also local, non-canonical signaling mediators have been described. Using a combination of genetic manipulations and functional assays we will determine the relevance of such non-canonical signaling components for synapse formation and plasticity.Common Goal 3: Interplay of neuronal activity and BMP signaling in synaptic plasticity and learningAn emerging theme of recent studies is a coupling of neuronal activity and BMP signaling. We will jointly test such functions at the Drosophila neuromuscular junction, in the pontocerebellar projection system, and in cortical microcircuits. These studies will seek to identify BMP signaling nodes modified by neuronal activity. Finally, we will directly test the relevance of BMP-signaling for activity-dependent structural plasticity and the learning processes.