title: Long-term habituation of the C-start escape response in zebrafish larvae.
abstract: The cellular and molecular basis of long-term memory in vertebrates remains poorly understood. Knowledge regarding long-term memory has been impeded by the enormous complexity of the vertebrate brain, particularly the mammalian brain, as well as by the relative complexity of the behavioral alterations examined in most studies of long-term memory in vertebrates. Here, we demonstrate a long-term form of nonassociative learning-specifically, long-term habituation (LTH)-of a simple reflexive escape response, the C-start, in zebrafish larvae. The C-start is triggered by the activation of one of a pair of giant neurons in the zebrafish's hindbrain, the Mauthner cells. We show that LTH of the C-start requires the activity of NMDA receptors and involves macromolecular synthesis. We further show that the long-term habituated reflex can by rapidly dishabituated by a brief tactile stimulus. Our results set the stage for rigorous, mechanistic investigations of the long-term memory for habituation of a reflexive behavioral response, one that is mediated by a relatively simple, neurobiologically tractable, neural circuit. Moreover, the demonstration of NMDAR and transcriptionally dependent LTH in a translucent vertebrate organism should facilitate the use of optical recording, and optogenetic manipulation, of neuronal activity to elucidate the cellular basis of a long-term vertebrate memory.
authors.affiliation: Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, United States.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Roberts
authors.affiliation: Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, United States.
authors.forename: Kaycey C
authors.initials: KC
authors.lastname: Pearce
authors.affiliation: Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, United States.
authors.forename: Ronny C
authors.initials: RC
authors.lastname: Choe
authors.affiliation: Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, United States.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Alzagatiti
authors.affiliation: Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, United States.
authors.forename: Anthony K
authors.initials: AK
authors.lastname: Yeung
authors.affiliation: Center for Autism Research and Program in Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, United States; Department of Psychiatry, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States; Department of Biology, University of Texas at Tyler, Tyler, TX, United States.
authors.forename: Brent R
authors.initials: BR
authors.lastname: Bill
authors.affiliation: Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, United States; Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States; Integrative Center for Learning and Memory, Brain Research Institute, University of California Los Angeles, Los Angeles, CA, United States. Electronic address: dglanzman@physci.ucla.edu.
authors.forename: David L
authors.initials: DL
authors.lastname: Glanzman
mesh_terms: D000818:Animals; D006185:Habituation, Psychophysiologic / Q000502:physiology*; D007814:Larva; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012018:Reflex / Q000502:physiology*; D015027:Zebrafish / Q000502:physiology*; D029961:Zebrafish Proteins
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D029961:Zebrafish Proteins
keywords: Habituation; Learning; Memory; NMDAR; Zebrafish