title: Haploinsufficiency of VGluT1 but not VGluT2 impairs extinction of spatial preference and response suppression.
abstract: The excitatory neurotransmitter l-glutamate is transported into synaptic vesicles by vesicular glutamate transporters (VGluTs) to transmit glutamatergic signals. Changes in their expression have been linked to various brain disorders including schizophrenia, Parkinson's, and Alzheimer's disease. Deleting either the VGluT1 or VGluT2 gene leads to profound developmental and neurological complications and early death, but mice heterozygous for VGluT1 or VGluT2 are viable and thrive. Acquisition, retention and extinction of conditioned visuospatial and emotional responses were compared between VGluT1(+/-) and VGluT2(+/-) mice, and their wildtype littermates, using different water maze procedures, appetitive scheduled conditioning, and conditioned fear protocols. The distinct brain expression profiles of the VGluT1 and -2 isoforms particularly in telencephalic structures, such as neocortex, hippocampus and striatum, are reflected in very specific behavioral changes. VGluT2(+/-) mice were unimpaired in spatial learning tasks and fear extinction. Conversely, VGluT1(+/-) mice displayed spatial extinction learning deficits and markedly impaired fear extinction. These data indicate that VGluT1, but not VGluT2, plays a role in the neural processes underlying inhibitory learning.
authors: Laboratory of Biological Psychology, University of Leuven, B-3000 Leuven, Belgium. zsuzsanna.vegh@ppw.kuleuven.be
authors: Zsuzsanna
authors: Z
authors: Callaerts-Vegh
authors: Diederik
authors: D
authors: Moechars
authors: Nathalie
authors: N
authors: Van Acker
authors: Guy
authors: G
authors: Daneels
authors: Ilse
authors: I
authors: Goris
authors: Sandra
authors: S
authors: Leo
authors: Arne
authors: A
authors: Naert
authors: Theo
authors: T
authors: Meert
authors: Detlef
authors: D
authors: Balschun
authors: Rudi
authors: R
authors: D'Hooge
mesh_terms: D000818:Animals; D001066:Appetite; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D001923:Brain Chemistry / Q000235:genetics; D004644:Emotions / Q000502:physiology; D005108:Extinction, Psychological / Q000502:physiology*; D007150:Immunohistochemistry; D007858:Learning / Q000502:physiology; D018782:Maze Learning / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D012055:Reinforcement Schedule; D013028:Space Perception / Q000502:physiology*; D050598:Vesicular Glutamate Transport Protein 1 / Q000172:deficiency / Q000235:genetics*; D050599:Vesicular Glutamate Transport Protein 2 / Q000172:deficiency / Q000235:genetics*
chemical_list: C493477:Slc17a6 protein, mouse; C493465:Slc17a7 protein, mouse; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2