title: Deletion of forebrain glycine transporter 1 enhances conditioned freezing to a reliable, but not an ambiguous, cue for threat in a conditioned freezing paradigm.
abstract: Enhanced expression of Pavlovian aversive conditioning but not appetitive conditioning may indicate a bias in the processing of threatening or fearful events. Mice with disruption of glycine transporter 1 (GlyT1) in forebrain neurons exhibit such a bias, but they are at the same time highly sensitive to manipulations that hinder the development of the conditioned response (CR) suggesting that the mutation may modify higher cognitive processes that extract predictive information between environmental cues. Here, we further investigated the development of fear conditioning in forebrain neuronal GlyT1 knockout mice when the predictiveness of a tone stimulus for foot-shock was rendered ambiguous by interspersing [tone→no shock] trials in-between [tone→shock] trials during acquisition. The CR to the ambiguous tone CS (conditioned stimulus) was compared with that generated by an unambiguous CS that was always followed by the shock US (unconditioned stimulus) during acquisition. We showed that rendering the CS ambiguous as described significantly attenuated the CR in the mutants, but it was not sufficient to modify the CR in the control mice. It is concluded that disruption of GlyT1 in forebrain neurons does not increase the risk of forming spurious and potentially maladaptive fear associations.
authors.affiliation: Laboratory of Behavioural Neurobiology, Swiss Federal Institute of Technology, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland; Laboratory of Behavioral Neuroscience, Legacy Research Institute, 1225 NE Second Avenue, Portland, OR 97232, United States.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Dubroqua
authors.affiliation: Laboratory of Behavioural Neurobiology, Swiss Federal Institute of Technology, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland; Laboratory of Behavioral Neuroscience, Legacy Research Institute, 1225 NE Second Avenue, Portland, OR 97232, United States.
authors.forename: Philipp
authors.initials: P
authors.lastname: Singer
authors.affiliation: Laboratory of Behavioural Neurobiology, Swiss Federal Institute of Technology, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland; Laboratory of Behavioral Neuroscience, Legacy Research Institute, 1225 NE Second Avenue, Portland, OR 97232, United States. Electronic address: benjamin.yee@trinity.oxon.org.
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Yee
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology*; D003463:Cues; D005239:Fear / Q000502:physiology*; D005260:Female; D017353:Gene Deletion; D050487:Glycine Plasma Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D016548:Prosencephalon / Q000502:physiology*
chemical_list: D050487:Glycine Plasma Membrane Transport Proteins; C493267:Slc6a9 protein, mouse
keywords: Fear; Glutamate; Glycine reuptake; Learning; NMDA receptor; Pavlovian conditioning