ON selectivity in Drosophila vision is a multisynaptic process involving both glutamatergic and GABAergic inhibition
Abstract
Sensory systems sequentially extract increasingly complex features. ON and OFF pathways, for example, encode increases or decreases of a stimulus from a common input. This ON/OFF pathway split is thought to occur at individual synaptic connections through a sign-inverting synapse in one of the pathways. Here, we show that ON selectivity is a multisynaptic process in the Drosophila visual system. A pharmacogenetics approach demonstrates that both glutamatergic inhibition through GluClα and GABAergic inhibition through Rdl mediate ON responses. Although neurons postsynaptic to the glutamatergic ON pathway input L1 lose all responses in GluClα mutants, they are resistant to a cell-type-specific loss of GluClα. This shows that ON selectivity is distributed across multiple synapses, and raises the possibility that cell-type-specific manipulations might reveal similar strategies in other sensory systems. Thus, sensory coding is more distributed than predicted by simple circuit motifs, allowing for robust neural processing.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files.
-
RNA sequencing of Drosophila melanogaster optic lobe cell types.NCBI Gene Expression Omnibus, GSE103772.
-
A GENETIC, GENOMIC, AND COMPUTATIONAL RESOURCE FOR EXPLORING NEURAL CIRCUIT FUNCTIONNCBI Gene Expression Omnibus, GSE116969.
Article and author information
Author details
Funding
Deutsche Forschungsgemeinschaft (Emmy Noether SI 1991/1-1)
- Miriam Henning
- Burak Gür
- Junaid Akhtar
- Marion Silies
Deutsche Forschungsgemeinschaft (SFB889)
- Sebastian Molina-Obando
- Juan Felipe Vargas-Fique
Deutsche Forschungsgemeinschaft (Project C08)
- Sebastian Molina-Obando
- Juan Felipe Vargas-Fique
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Claude Desplan, New York University, United States
Version history
- Received: June 16, 2019
- Accepted: September 18, 2019
- Accepted Manuscript published: September 19, 2019 (version 1)
- Version of Record published: November 11, 2019 (version 2)
Copyright
© 2019, Molina-Obando et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 3,743
- views
-
- 525
- downloads
-
- 30
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Neuroscience
Abnormal activity in the cerebellar nuclei can be used to predict motor symptoms and induce them experimentally, pointing to potential therapeutic strategies.
-
- Cell Biology
- Neuroscience
One of the most extensively studied members of the Ras superfamily of small GTPases, Rac1 is an intracellular signal transducer that remodels actin and phosphorylation signaling networks. Previous studies have shown that Rac1-mediated signaling is associated with hippocampal-dependent working memory and longer-term forms of learning and memory and that Rac1 can modulate forms of both pre- and postsynaptic plasticity. How these different cognitive functions and forms of plasticity mediated by Rac1 are linked, however, is unclear. Here, we show that spatial working memory in mice is selectively impaired following the expression of a genetically encoded Rac1 inhibitor at presynaptic terminals, while longer-term cognitive processes are affected by Rac1 inhibition at postsynaptic sites. To investigate the regulatory mechanisms of this presynaptic process, we leveraged new advances in mass spectrometry to identify the proteomic and post-translational landscape of presynaptic Rac1 signaling. We identified serine/threonine kinases and phosphorylated cytoskeletal signaling and synaptic vesicle proteins enriched with active Rac1. The phosphorylated sites in these proteins are at positions likely to have regulatory effects on synaptic vesicles. Consistent with this, we also report changes in the distribution and morphology of synaptic vesicles and in postsynaptic ultrastructure following presynaptic Rac1 inhibition. Overall, this study reveals a previously unrecognized presynaptic role of Rac1 signaling in cognitive processes and provides insights into its potential regulatory mechanisms.