title: Neuronal calcium sensor-1 deletion in the mouse decreases motivation and dopamine release in the nucleus accumbens.
abstract: Calcium sensors detect intracellular calcium changes and interact with downstream targets to regulate many functions. Neuronal Calcium Sensor-1 (NCS-1) or Frequenin is widely expressed in the nervous system, and involved in neurotransmission, synaptic plasticity and learning. NCS-1 interacts with and regulates dopamine D2 receptor (D2R) internalization and is implicated in disorders like schizophrenia and substance abuse. However, the role of NCS-1 in behaviors dependent on dopamine signaling in the striatum, where D2R is most highly expressed, is unknown. We show that Ncs-1 deletion in the mouse decreases willingness to work for food. Moreover, Ncs-1 knockout mice have significantly lower activity-dependent dopamine release in the nucleus accumbens core in acute slice recordings. In contrast, food preference, responding for conditioned reinforcement, ability to represent changes in reward value, and locomotor response to amphetamine are not impaired. These studies identify novel roles for NCS-1 in regulating activity-dependent striatal dopamine release and aspects of motivated behavior.
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, M5 G 15 Toronto, Canada; Institute of Medical Science, University of Toronto, M5S 1A8 Toronto, Canada.
authors.forename: Enoch
authors.initials: E
authors.lastname: Ng
authors.affiliation: Departments of Pharmacology and Neurosciences, Université de Montréal, H3C 3J7 Montréal, Canada.
authors.forename: Rafael K
authors.initials: RK
authors.lastname: Varaschin
authors.affiliation: Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, M5T 1R8 Toronto, Canada.
authors.forename: Ping
authors.initials: P
authors.lastname: Su
authors.affiliation: Department of Psychology, University of Toronto, M5S 3G3 Toronto, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, M5T 1R8 Toronto, Canada.
authors.forename: Caleb J
authors.initials: CJ
authors.lastname: Browne
authors.affiliation: Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, D-20251 Hamburg, Germany.
authors.forename: Joanna
authors.initials: J
authors.lastname: Hermainski
authors.affiliation: Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, M5T 1R8 Toronto, Canada; Department of Psychiatry, University of Toronto, M5T 1R8 Toronto, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Le Foll
authors.affiliation: Institute of Physiology, University of the Saarland, 66424 Homburg, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Pongs
authors.affiliation: Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, M5T 1R8 Toronto, Canada; Department of Psychiatry, University of Toronto, M5T 1R8 Toronto, Canada.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Departments of Pharmacology and Neurosciences, Université de Montréal, H3C 3J7 Montréal, Canada.
authors.forename: Louis-Eric
authors.initials: LE
authors.lastname: Trudeau
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, M5 G 15 Toronto, Canada; Department of Molecular Genetics, University of Toronto, M5S 1A8 Toronto, Canada.
authors.forename: John C
authors.initials: JC
authors.lastname: Roder
authors.affiliation: Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, M5T 1R8 Toronto, Canada; Department of Psychiatry, University of Toronto, M5T 1R8 Toronto, Canada. Electronic address: albert.wong@utoronto.ca.
authors.forename: Albert H C
authors.initials: AH
authors.lastname: Wong
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003214:Conditioning, Classical / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D005247:Feeding Behavior / Q000502:physiology; D005518:Food Preferences / Q000502:physiology; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009042:Motivation / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051580:Neuronal Calcium-Sensor Proteins / Q000235:genetics / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000378:metabolism*; D012528:Satiety Response / Q000502:physiology; D046509:Tissue Culture Techniques
chemical_list: D000697:Central Nervous System Stimulants; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; C101464:frequenin calcium sensor proteins; D000661:Amphetamine; D004298:Dopamine
keywords: Dopamine; Effort; Frequenin; Motivation; Neuronal calcium sensor-1; Progressive ratio