title: A Subtype of Olfactory Bulb Interneurons Is Required for Odor Detection and Discrimination Behaviors.
abstract: Neural circuits that undergo reorganization by newborn interneurons in the olfactory bulb (OB) are necessary for odor detection and discrimination, olfactory memory, and innate olfactory responses, including predator avoidance and sexual behaviors. The OB possesses many interneurons, including various types of granule cells (GCs); however, the contribution that each type of interneuron makes to olfactory behavioral control remains unknown. Here, we investigated the in vivo functional role of oncofetal trophoblast glycoprotein 5T4, a regulator for dendritic arborization of 5T4-expressing GCs (5T4 GCs), the level of which is reduced in the OB of 5T4 knock-out (KO) mice. Electrophysiological recordings with acute OB slices indicated that external tufted cells (ETCs) can be divided into two types, bursting and nonbursting. Optogenetic stimulation of 5T4 GCs revealed their connection to both bursting and nonbursting ETCs, as well as to mitral cells (MCs). Interestingly, nonbursting ETCs received fewer inhibitory inputs from GCs in 5T4 KO mice than from those in wild-type (WT) mice, whereas bursting ETCs and MCs received similar inputs in both mice. Furthermore, 5T4 GCs received significantly fewer excitatory inputs in 5T4 KO mice. Remarkably, in olfactory behavior tests, 5T4 KO mice had higher odor detection thresholds than the WT, as well as defects in odor discrimination learning. Therefore, the loss of 5T4 attenuates inhibitory inputs from 5T4 GCs to nonbursting ETCs and excitatory inputs to 5T4 GCs, contributing to disturbances in olfactory behavior. Our novel findings suggest that, among the various types of OB interneurons, the 5T4 GC subtype is required for odor detection and discrimination behaviors.
  
  
  
  Neuronal circuits in the brain include glutamatergic principal neurons and GABAergic interneurons. Although the latter is a minority cell type, they are vital for normal brain function because they regulate the activity of principal neurons. If interneuron function is impaired, brain function may be damaged, leading to behavior disorder. The olfactory bulb (OB) possesses various types of interneurons, including granule cells (GCs); however, the contribution that each type of interneuron makes to the control of olfactory behavior remains unknown. Here, we analyzed electrophysiologically and behaviorally the function of oncofetal trophoblast glycoprotein 5T4, a regulator for dendritic branching in OB GCs. We found that, among the various types of OB interneuron, the 5T4 GC subtype is required for odor detection and odor discrimination behaviors.
authors.affiliation: Laboratory for Molecular Biology of Neural System, Advanced Medical Research Center.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Physiology I, and.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ogawa
authors.affiliation: Laboratory for Molecular Biology of Neural System, Advanced Medical Research Center.
authors.forename: Sei-Ichi
authors.identifier: 0000-0002-8453-1786
authors.initials: S
authors.lastname: Yoshihara
authors.affiliation: Laboratory for Molecular Biology of Neural System, Advanced Medical Research Center.
authors.forename: Ryo
authors.initials: R
authors.lastname: Asahina
authors.affiliation: Laboratory for Molecular Biology of Neural System, Advanced Medical Research Center.
authors.forename: Masahito
authors.initials: M
authors.lastname: Kinoshita
authors.affiliation: Laboratory for Molecular Biology of Neural System, Advanced Medical Research Center.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Kitano
authors.affiliation: Laboratory for Molecular Biology of Neural System, Advanced Medical Research Center.
authors.forename: Michiko
authors.initials: M
authors.lastname: Kitsuki
authors.affiliation: Laboratory for Molecular Biology of Neural System, Advanced Medical Research Center.
authors.forename: Kana
authors.initials: K
authors.lastname: Tatsumi
authors.affiliation: Laboratory for Molecular Biology of Neural System, Advanced Medical Research Center.
authors.forename: Mamiko
authors.initials: M
authors.lastname: Okuda
authors.affiliation: Department of Anatomy II, Nara Medical University School of Medicine, Kashihara, Nara 634-8521, Japan.
authors.forename: Kouko
authors.identifier: 0000-0001-6230-2803
authors.initials: K
authors.lastname: Tatsumi
authors.affiliation: Department of Anatomy II, Nara Medical University School of Medicine, Kashihara, Nara 634-8521, Japan.
authors.forename: Akio
authors.identifier: 0000-0001-9951-9862
authors.initials: A
authors.lastname: Wanaka
authors.affiliation: Department of Neurophysiology, Gunma University Graduate School of Medicine, Gunma 371-8511, Japan, and.
authors.forename: Hirokazu
authors.identifier: 0000-0002-0721-4293
authors.initials: H
authors.lastname: Hirai
authors.affiliation: Institute of Cancer Sciences, Paterson Building, University of Manchester, Manchester M20 4BX, United Kingdom.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Stern
authors.affiliation: Laboratory for Molecular Biology of Neural System, Advanced Medical Research Center, atsuboi@naramed-u.ac.jp.
authors.forename: Akio
authors.identifier: 0000-0002-4790-4512
authors.initials: A
authors.lastname: Tsuboi
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D004193:Discrimination Learning / Q000502:physiology; D007395:Interneurons / Q000145:classification / Q000166:cytology* / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009812:Odorants / Q000032:analysis*; D009830:Olfactory Bulb / Q000166:cytology* / Q000196:embryology / Q000502:physiology*; D055696:Olfactory Perception / Q000502:physiology*
keywords: dendritic arborization; odor detection; odor discrimination; olfactory bulb interneuron; optogenetics; transmembrane protein