Current Research

Our research targets the physiological, cellular and molecular mechanisms underlying experiencedependent synaptic plasticity in Drosophila. Fundamental for this research are two complementary experimental approaches:
A) The neuromuscular junctions (NMJs) of Drosophila larvae represent exceptionally well accessible glutamatergic synapses, which allow in vivo behavioral stimulation and a highly resolved physiological, morphological and molecular analysis of the mechanisms underlying experience-dependent synaptic potentiation.

Schuster Fig1
Fig. 1: Development of larval NMJs of Drosophila. Developing neuromuscular junction of a Drosophila embryo (A, 12 h after egg laying) and larvae (B-D) at different developmental stages (B: 24 h after egg laying; C: 2 days after egg laying, D: 4 days after egg laying). ( A) Growth cone of the motoneuron aCC extends dorsally towards its target muscle 1. ( B) The growth cone has transformed to presynaptic specialisations of NMJs. These NMJs harbour functionally mature synapses. (C, D) Growth of NMJs during further larval development. NMJs were labelled with an antibody recognising the cell adhesion molecule Fasciclin II. Scale bars: 10 μm (A), (B-C); 20 μm (D). (from Schuster et al., 1996a)


B) Olfactory fear conditioning of adult flies is a well established paradigm to elicit and analyze various forms of memory (including long-term memory; Fig. 2) and memory modification (such as extinction).

Schuster Fig2
Fig. 2.Dissection of memory phases. At the behavioral level, the observed decay of memory appears relatively seamless (black). Experimental disruptions in numerous animal species including humans, however, reveal temporally, mechanistically and anatomically distinct phases underlying memory retention. In Drosophila, at least four mechanistically distinct phases have been described. These are short-term memory (STM; green), middle-term memory (MTM; blue) anesthesia-resistant memory (ARM; purple) and long-term memory (LTM; red).


Both approaches greatly benefit from the powerful genetic tools available in Drosophila and the possibility to transfer the mechanisms identified in the high-resolution model NMJ to higher brain functions and vice versa. Experience-dependent potentiation of synaptic transmission The crawling activities of Drosophila larvae show large individual differences over time. These differences in crawling profiles are associated with differences in the usage of the glutamatergic neuromuscular synapses and can therefore be used to systematically assess potential experience-dependent synaptic changes. Based on this strategy we have recently shown that the strength of glutamatergic transmission can undergo robust and long-lasting potentiation in an experience-dependent manner.

Schuster Fig3
Fig. 3. Phase-I and phase-II of experience-dependent synaptic potentiation. (A) Following the transfer of size-matched fooddigging third instar larvae onto a moist, food-free surface, larvae show variable crawling activities. The crawling profiles of two larvae exhibiting persistently high (filled squares) or low crawling activities (open squares) are shown. (B-C) Representative traces of mEJPs (B) and eEJPs (C). (D-E) Time course of crawling-induced amplitude changes of eEJPs (D) and mEJPs (E) of ‘fast’ and ‘slow’ crawling individuals (filled and open symbols, respectively). The presence or absence of changes in the mEJP amplitude and enhanced eEJPs define phase-I and phase-II of synaptic potentiation. Data represent mean ± S.E.M. of 9-19 larvae per data point. **p<0.01; *p<0.05.


This potentiation is mediated by several different synaptic mechanisms, which based on their temporal appearance define a hierarchy of several discrete phases of experiencedependent synaptic potentiation [4]. In this project we characterize the physiological and molecular mechanisms underlying experience-dependent synaptic potentiation. We are currently focusing on the following topics:
• Experience-dependent regulation of presynaptic quantal size
• Role of presynaptic mGluRs in the regulation and release of large vesicles • Experience-dependent regulation of the functional balance of postsynaptic GluRs
• Experience-dependent regulation of postsynaptic NOsynthase (NOS) activity
• Presynaptic NMDARs and their effect on the probability of vesicle release
• Ca2+-dynamics in the pre- and postsynaptic terminal during experience-dependent potentiation
• Role of NOS-activity in the structural organization of synapses
• Experience-dependent synaptic protein synthesis and morphological consolidation of synaptic potentiation
• Development of a computational model of a simple network of glutamatergic synapses Long-term memory formation and LTM extinction in Drosophila Animals can store information based on their individual experiences. Yet not all information is stored for long periods of time. Rather, it is the most intense or even traumatic events, or the most repeated information, that is eventually encoded in long-term memory (LTM). LTM itself and/or access to the stored information is continually modified by experience, re-enforced through reconsolidation or diminished through extinction. Despite of an increasing general interest in these phenomena the underlying cell biological or molecular mechanisms are poorly understood. The fruit fly Drosophila has served as a model system for studying various forms of learning and memory, particularly for those evoked by Pavlovian conditioning, largely because of the power of its genetic tools, its smaller central nervous system and fewer molecular redundancies when compared to mammals. Identifying the principal mechanisms underlying LTM formation, consolidation, recall and extinction should facilitate a better understanding of similar processes in mammals and may guide towards novel treatments of psychopathological conditions. Based on established olfactory fear conditioning paradigms we are currently focusing on the following topics:
• Signaling events involved in the formation, consolidation and recall of LTM
• Mapping of LTM traces in the fly brain
• Role of NMDARs in LTM
• Characterization of LTM extinction
• Mapping of circuits and neurons involved in LTM extinction
• Signaling pathways involved in the formation of extinction memory
• Pharmacological and molecular interference with LTM extinction

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Latest Revision: 2012-08-02
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