Projects
Disease mediated modification of neuronal circuits
Neurons share common features, such as electrical excitability and synaptic inter neuron communication. However, the individual entities within a neuronal network exhibit extensive diversity shaped by intrinsic cellular programs and elaborate sequential mechanisms during development, specifying their neuronal identity. Recently, it was shown that transient overexpression of transcription factors can stably reprogram cells from one lineage to another without cell division. This raises the question whether neuronal identity and diversity may be modified outside the context of development of the brain. And, whether reprogramming may occur in neuronal entities of neuronal circuits subsequently to neuro-degeneration, e.g. Parkinson’s disease (PD), allowing for compensation of neuronal loss of their interaction partners within the degenerating neuronal circuit.
Our previous studies show that altered dopamine signaling leads to modifications of serotonin neuron projections onto their target neuropils in the fully developed Drosophila brain. This observation allows for speculations that the identity of a neuronal entity does not solely dependent on intrinsic cellular programs during development but may also depend on environmental cues within its fully developed neuronal network.
Employing a combination of immunohistochemistry, optophysiology, thermogenetic neuron activation, as well as single cell transcriptomics methods our research aims at understanding the molecular mechanisms that underly these observed alterations in the dopaminergic and serotoninergic system.
Studying the neuronal circuits that compensate for alterations in signaling among different neuro-transmitters within the same circuit will help a better understanding maladaptive interneuron communication due to neuro-degeneration, as well as pharmacological treatment of neurodegenerative diseases, such as Parkinson’s disease.
Developmental assembly of mushroom body circuits during metamorphosis
(Collaborative Project with Prof. Oren Schuldiner, Weizmann Institute, Rehovot, Israel)
Targeting of axons and dendrites is critical for circuit formation and its subsequent comme il faut functionality. Studies in the last four decades have shown that post-embryonic remodeling of neural circuits is a key strategy to refine functional circuits across animal kingdoms. Remodeling can be envisioned as the last step in the development of neural circuits but how exactly neuronal circuits wire together and how functional compartmentalization within the same neuronal entity in the circuit during development is achieved is a fundamental problem in neuroscience that is still only partially understood.
The Drosophila mushroom body γ-lobe offers a unique system to study such processes. It harbors five distinct subcellular compartments defined by localized innervations of neuronal sub-types of different functional significance. Propoer γ4/5 compartmentalization depends on proper IgSF protein signaling between the mushroom body γ-lobes and the according IgSF protein interaction partner that is expressed in synaptically across situated subsets of dopamine producing neurons.
Understanding the role interneural communication plays in circuit development and in the subsequent function of the circuit will provide broader insights into circuit formation and function during development and disease. The proposed collaborative project aims at understanding molecular and cellular mechanisms underlying neuronal remodeling and which role IgSF molecules play in interneuronal communication during the reformation of MB circuits during pupal development in Drosophila melanogaster.
