High order unimodal olfactory sensory preconditioning in Drosophila

  1. Juan Martinez-Cervantes
  2. Prachi Shah
  3. Anna Phan
  4. Isaac Cervantes-Sandoval  Is a corresponding author
  1. Georgetown University, United States
  2. University of Alberta, Canada

Abstract

Learning and memory storage is a complex process that has proven challenging to tackle. It is likely that, in nature, the instructive value of reinforcing experiences is acquired rather than innate. The association between seemingly neutral stimuli increases the gamut of possibilities to create meaningful associations and the predictive power of moment-by-moment experiences. Here we report physiological and behavioral evidence of olfactory unimodal sensory preconditioning in fruit flies. We show that the presentation of a pair of odors (S1 and S2) before one of them (S1) is associated with electric shocks elicits a conditional response not only to the trained odor (S1) but to the odor previously paired with it (S2). This occurs even if the S2 odor was never presented in contiguity with the aversive stimulus. In addition, we show that inhibition of the small G protein Rac1, a known forgetting regulator, facilitates the association between S1/S2 odors. These results indicate that flies can infer value to olfactory stimuli based on the previous associative structure between odors, and that inhibition of Rac1 lengthens the time window of the olfactory 'sensory buffer', allowing the establishment of associations between odors presented in sequence.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Juan Martinez-Cervantes

    Department of Biology, Georgetown University, Washington, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Prachi Shah

    Department of Biology, Georgetown University, Washington, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Anna Phan

    Department of Biological Sciences, University of Alberta, Edmonton, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Isaac Cervantes-Sandoval

    Department of Biology, Georgetown University, Washington, United States
    For correspondence
    ic400@georgetown.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6372-7288

Funding

National Institute of Mental Health (R21MH117485-01A1)

  • Isaac Cervantes-Sandoval

Brain and Behavior Research Foundation (30442)

  • Isaac Cervantes-Sandoval

National Institute on Aging (T32AG071745)

  • Prachi Shah

Georgetown University (ID162838)

  • Isaac Cervantes-Sandoval

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Sonia Sen, Tata Institute for Genetics and Society, India

Version history

  1. Preprint posted: November 30, 2021 (view preprint)
  2. Received: March 31, 2022
  3. Accepted: September 18, 2022
  4. Accepted Manuscript published: September 21, 2022 (version 1)
  5. Version of Record published: October 13, 2022 (version 2)

Copyright

© 2022, Martinez-Cervantes 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

  • 1,266
    views
  • 377
    downloads
  • 8
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

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)

  1. Juan Martinez-Cervantes
  2. Prachi Shah
  3. Anna Phan
  4. Isaac Cervantes-Sandoval
(2022)
High order unimodal olfactory sensory preconditioning in Drosophila
eLife 11:e79107.
https://doi.org/10.7554/eLife.79107

Share this article

https://doi.org/10.7554/eLife.79107

Further reading

    1. Developmental Biology
    2. Neuroscience
    Melody C Iacino, Taylor A Stowe ... Mark J Ferris
    Research Article

    Adolescence is characterized by changes in reward-related behaviors, social behaviors, and decision making. These behavioral changes are necessary for the transition into adulthood, but they also increase vulnerability to the development of a range of psychiatric disorders. Major reorganization of the dopamine system during adolescence is thought to underlie, in part, the associated behavioral changes and increased vulnerability. Here, we utilized fast scan cyclic voltammetry and microdialysis to examine differences in dopamine release as well as mechanisms that underlie differential dopamine signaling in the nucleus accumbens (NAc) core of adolescent (P28-35) and adult (P70-90) male rats. We show baseline differences between adult and adolescent stimulated dopamine release in male rats, as well as opposite effects of the a6 nicotinic acetylcholine receptor (nAChR) on modulating dopamine release. The a6-selective blocker, a-conotoxin, increased dopamine release in early adolescent rats, but decreased dopamine release in rats beginning in middle adolescence and extending through adulthood. Strikingly, blockade of GABAA and GABAB receptors revealed that this a6-mediated increase in adolescent dopamine release requires NAc GABA signaling to occur. We confirm the role of a6 nAChR and GABA in mediating this effect in vivo using microdialysis. Results herein suggest a multisynaptic mechanism potentially unique to the period of development that includes early adolescence, involving acetylcholine acting at a6-containing nAChRs to drive inhibitory GABA tone on dopamine release.

    1. Neuroscience
    Jongkyun Kang, Guodong Huang ... Jie Shen
    Research Article

    Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson’s disease (PD). However, whether LRRK2 mutations cause PD and degeneration of dopaminergic (DA) neurons via a toxic gain-of-function or a loss-of-function mechanism is unresolved and has pivotal implications for LRRK2-based PD therapies. In this study, we investigate whether Lrrk2 and its functional homolog Lrrk1 play a cell-intrinsic role in DA neuron survival through the development of DA neuron-specific Lrrk conditional double knockout (cDKO) mice. Unlike Lrrk germline DKO mice, DA neuron-restricted Lrrk cDKO mice exhibit normal mortality but develop age-dependent loss of DA neurons, as shown by the progressive reduction of DA neurons in the substantia nigra pars compacta (SNpc) at the ages of 20 and 24 months. Moreover, DA neurodegeneration is accompanied with increases in apoptosis and elevated microgliosis in the SNpc as well as decreases in DA terminals in the striatum, and is preceded by impaired motor coordination. Taken together, these findings provide the unequivocal evidence for the cell-intrinsic requirement of LRRK in DA neurons and raise the possibility that LRRK2 mutations may impair its protection of DA neurons, leading to DA neurodegeneration in PD.