RRC ID 70722
Author Georganta EM, Moressis A, Skoulakis EMC.
Title Associative Learning Requires Neurofibromin to Modulate GABAergic Inputs to Drosophila Mushroom Bodies.
Journal J Neurosci
Abstract Cognitive dysfunction is among the hallmark symptoms of Neurofibromatosis 1, and accordingly, loss of the Drosophila melanogaster ortholog of Neurofibromin 1 (dNf1) precipitates associative learning deficits. However, the affected circuitry in the adult CNS remained unclear and the compromised mechanisms debatable. Although the main evolutionarily conserved function attributed to Nf1 is to inactivate Ras, decreased cAMP signaling on its loss has been thought to underlie impaired learning. Using mixed sex populations, we determine that dNf1 loss results in excess GABAergic signaling to the central for associative learning mushroom body (MB) neurons, apparently suppressing learning. dNf1 is necessary and sufficient for learning within these non-MB neurons, as a dAlk and Ras1-dependent, but PKA-independent modulator of GABAergic neurotransmission. Surprisingly, we also uncovered and discuss a postsynaptic Ras1-dependent, but dNf1-independnet signaling within the MBs that apparently responds to presynaptic GABA levels and contributes to the learning deficit of the mutants.
Volume 41(24)
Pages 5274-5286
Published 2021-6-16
DOI 10.1523/JNEUROSCI.1605-20.2021
PII JNEUROSCI.1605-20.2021
PMID 33972401
PMC PMC8211548
MeSH Animals Association Learning / physiology* Cyclic AMP / metabolism Drosophila Proteins / metabolism* Drosophila melanogaster Mushroom Bodies / metabolism* Nerve Tissue Proteins / metabolism* Signal Transduction / physiology gamma-Aminobutyric Acid / metabolism* ras GTPase-Activating Proteins / metabolism* ras Proteins / metabolism
IF 5.674
Drosophila DGRC#104937