Dlg Is Required for Short-Term Memory and Interacts with NMDAR in the Drosophila Brain

Abstract

The vertebrates’ scaffold proteins of the Dlg-MAGUK family are involved in the recruitment, clustering, and anchoring of glutamate receptors to the postsynaptic density, particularly the NMDA subtype glutamate-receptors (NRs), necessary for long-term memory and LTP. In Drosophila, the only gene of the subfamily generates two main products, dlgA, broadly expressed, and dlgS97, restricted to the nervous system. In the Drosophila brain, NRs are expressed in the adult brain and are involved in memory, however, the role of Dlg in these processes and its relationship with NRs has been scarcely explored. Here, we show that the dlg mutants display defects in short-term memory in the olfactory associative-learning paradigm. These defects are dependent on the presence of DlgS97 in the Mushroom Body (MB) synapses. Moreover, Dlg is immunoprecipitated with NRs in the adult brain. Dlg is also expressed in the larval neuromuscular junction (NMJ) pre and post-synaptically and is important for development and synaptic function, however, NR is absent in this synapse. Despite that, we found changes in the short-term plasticity paradigms in dlg mutant larval NMJ. Together our results show that larval NMJ and the adult brain relies on Dlg for short-term memory/plasticity, but the mechanisms differ in the two types of synapses.

Skewing information flow through pre- and postsynaptic plasticity in the mushroom bodies ofDrosophila

“…A further analogy of plasticity mechanisms is the involvement of Dlg (the conserved PSD-95 ortholog), in regulating α2 protein levels at MBON dendrites ( Pribbenow et al 2022 ), potentially by interacting with the receptors at the postsynapse. Besides PSD-95's involvement in memory-related plasticity at glutamatergic vertebrate synapses, Dlg is involved in glutamate receptor plasticity at the Drosophila neuromuscular junction ( Chen and Featherstone 2005 ; Thomas et al 2010 ) and, in addition, is required in other pathways for associative memory formation in Drosophila ( Bertin et al 2022 ). Of note, at the level of α′3 MBONs (MBON-α′3ap, MBON-α′3m), postsynaptic plasticity induced by familiarity learning also requires the α5 nAChR subunit upstream of the α2 subunit ( Pribbenow et al 2022 ).…”