About

Dr. Ralph J. Greenspan has worked on the genetic basis of behavior and brain function in fruit flies (Drosophila melanogaster) almost since the inception of the field, studying with one of its founders, Jeffery Hall, at Brandeis University in Massachusetts, where he received his Ph.D. in biology in 1979. He is currently the Director of the Center for Brain Activity Mapping of the Kavli Institute for Brain and Mind at the University of California San Diego, and a Professor in the Division of Biology's Neurobiology Section. His research is broadly concerned with genetic aspects and approaches to studying brain and behavior in Drosophila, informed by the recognition that many of the problems require a systems level approach. He has developed apparatuses and strategies for recording real-time activity in the brains of behaving flies, including a light-field microscopy technique for recording from the entire fly brain at all levels simultaneously, and 2-photon recording during visual attention tasks. His work has contributed to understanding activation in specific brain regions related to visual memory formation and its modulation by distracting stimuli. Dr. Greenspan played a role in the White House BRAIN Initiative and spearheaded the establishment of the Cal-BRAIN program, serving as its Co-Director.

Research topics

• Neuroscience
• Biology
• Zoology
• Evolutionary biology
• Mathematics
• Chemistry
• Psychology
• Cognitive psychology
• Ecology
• Genetics

Selected publications

• Memoir of the early years of the CSHL summer <i>Drosophila</i> neurobiology course: 1984-1985

  Journal of Neurogenetics · 2024-09-02

  article1st authorCorresponding
  PublisherDOI

• Differential mechanisms underlie trace and delay conditioning in Drosophila

  Nature · 2022 · 63 citations

  Senior authorCorresponding
  • Neuroscience
  • Psychology
  • Cognitive psychology
  PublisherOA PDFDOI

• Publisher Correction: Differential mechanisms underlie trace and delay conditioning in Drosophila

  Nature · 2022-03-22

  erratumOpen accessSenior author
  PublisherOA PDFDOI

• Valence opponency in peripheral olfactory processing

  Proceedings of the National Academy of Sciences · 2022 · 37 citations

  • Neuroscience
  • Biology
  • Chemistry

  sensory hairs, wherein compartmentalized neurons inhibit each other via ephaptic coupling. Systematic behavioral assays reveal that most paired ORNs antagonistically regulate the same type of behavior. Such valence opponency is relevant in critical behavioral contexts including place preference, egg laying, and courtship. Odor-mixture experiments show that ephaptic inhibition provides a peripheral means for evaluating and shaping countervailing cues relayed to higher brain centers. Furthermore, computational modeling suggests that this organization likely contributes to processing ratio information in odor mixtures. This olfactory valence map may have evolved to swiftly process ethologically meaningful odor blends without involving costly synaptic computation.

  PublisherDOI

• In Vivo Brain Imaging in Freely Moving and Socially Interacting Drosophila

  Neuromethods · 2022-01-01

  book-chapterSenior author
  PublisherDOI

• Learning about quantitative genetics from Marla Sokolowski

  Journal of Neurogenetics · 2021-06-15

  article1st authorCorresponding

  Marla Sokolowski is a true pioneer in behavioral genetics, having made the first molecular delineation of a naturally occurring behavioral polymorphism in her work on the foraging locus in Drosophila melanogaster. The gene was subsequently found to be responsible for behavioral variants and types in many other species, both invertebrate and mammal (human). The path to get there is a paradigmatic example of how to use the power of genetic analysis, including some rather esoteric techniques, to zero in on a gene and delineate its molecular identity and its pleiotropic roles.

  PublisherDOI

• Anti-instinctive Learning Behavior Revealed by Locomotion-Triggered Mild Heat Stress in Drosophila

  Frontiers in Behavioral Neuroscience · 2020-04-07 · 11 citations

  articleOpen accessSenior authorCorresponding

  Anti-instinctive learning, an ability to modify an animal's innate behaviors in ways that go against one's innate tendency, can confer great evolutionary advantages to animals and enable them to better adapt to the changing environment. Yet, our understanding of anti-instinctive learning and its underlying mechanisms is still limited. In this work, we describe a new anti-instinctive learning behavior of fruit flies. This learning paradigm requires the fruit fly to respond to a recurring, aversive, mild heat stress by modifying its innate locomotion behavior. We found that experiencing movement-triggered mild heat stress repeatedly significantly reduced walking activity in wild type fruit flies, indicating that fruit flies are capable of anti-instinctive learning. We also report that such learning ability is reduced in dopamine 1-like receptor 1 (Dop1R1) null mutant and dopamine 2-like receptor (Dop2R) null mutant flies, suggesting that these two dopamine receptors are involved in mediating anti-instinctive learning in flies.

  PublisherOA PDFDOI

• Imaging brain activity during complex social behaviors in Drosophila with Flyception2

  Nature Communications · 2020 · 24 citations

  Senior authorCorresponding
  • Neuroscience
  • Biology
  • Evolutionary biology

  Optical in vivo recordings from freely walking Drosophila are currently possible only for limited behaviors. Here, we expand the range of accessible behaviors with a retroreflective marker-based tracking and ratiometric brain imaging system, permitting brain activity imaging even in copulating male flies. We discover that P1 neurons, active during courtship, are inactive during copulation, whereas GABAergic mAL neurons remain active during copulation, suggesting a countervailing role of mAL in opposing P1 activity during mating.

  PublisherOA PDFDOI

• Decision letter: Transgenerational inheritance of ethanol preference is caused by maternal NPF repression

  2019-02-26

  peer-reviewOpen accessSenior author
  PublisherDOI

• Genes as Bits for Nervous System Development

  Advances in Cognitive Science · 2019-04-23 · 1 citations

  book-chapterOpen access1st authorCorresponding

  Any attempt at constructing hypotheses concerning genetic strategies in nervous system development requires, as a minimal starting point, the defining of the informational units or genetic &quot;bits&quot; which take part in the process. That is, although may know that some number of genes take part, this implies no particular strategy because of the enormous variety of possible gene functions. The nematode nervous system is by far the most &quot;hard wired&quot; in the sense of having an invariant number and pattern of cells, derived by means of strict cell lineages with little or no plasticity or experience dependence in the final cellular patterns. The fly is intermediate, and, in some respects, may be an actual mixture. The zebrafish mutant ndg-1 exerts its effects on CNS neurons as opposed to peripheral ones, but only on certain classes in the CNS. The zebrafish mutant B-39 specifically causes muscle disorganization.

  PublisherDOI

Recent grants

• NIH Grant R01HD020083

  NIH · $493k · 1988

• NIH Grant R01GM087393

  NIH · $1.2M · 2014

• EAGER: Exploring Gene Network States

  NSF · $300k · 2010–2011

• CompBio: Gene Interactions as a Model for Network Architectures

  NSF · $550k · 2004–2007

• Brain Sites for CaM Kinase-Mediated Conditioning Defects in Drosophila

  NSF · $120k · 1996–1998

Frequent coauthors

• Jean‐François Ferveur

  Centre National de la Recherche Scientifique

  37 shared

• Bruno van Swinderen

  University of Queensland

  20 shared

• Zoya Katarova

  HUN-REN Institute of Experimental Medicine

  15 shared

• Gábor Szabó

  14 shared

• Giulio Tononi

  11 shared

• Takeo Katsuki

  University of California, San Diego

  11 shared

• Terrence J. Sejnowski

  11 shared

• Karl Deisseroth

  Stanford University

  10 shared

Labs

• Greenspan LabPI

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Education

• BA and PhD, Biology

  Brandeis University

  1979

Awards & honors

• White House Office of Science and Technology Policy White Pa…
• Co-Director of Cal-BRAIN program (2014)