Forebrain glycine transporter 1 deletion enhances sensitivity to CS-US discontiguity in classical conditioning.
The deletion of glycine transporter 1 (GlyT1) in forebrain neurons can apparently strengthen Pavlovian aversive conditioning, but this phenotype is not expressed if conditioning followed non-reinforced pre-exposures of the to-be-conditioned stimulus (CS). To examine whether GlyT1 disruption may only enhance aversive associative learning under conditions that most favour the formation of CS-US excitatory link, we evaluated the impact of GlyT1 disruption on the trace conditioning procedure whereby a trace interval between a tone CS and a shock US was introduced during conditioning. CS and US occurrences were thus rendered discontiguous, which was expected to impede conditioning compared with contiguous CS-US pairing. Conditioned freezing to the CS was measured in a retention test conducted 48 h after conditioning. The genetic disruption significantly modified the temporal dynamics of the freezing response over the course of the 8-min presentation of the CS, although the immediate conditioned response to the CS was unaffected. The separation between "trace" and "no-trace" conditions was augmented in the mutant mice, but this only became apparent in mid-session; and the augmentation can be attributed to the combined effects of (i) weaker conditioned freezing in the mutant relative to control subjects in the "trace" condition, and (ii) stronger conditioned freezing in mutants relative controls in the "no-trace" condition. The demonstrated increased sensitivity to the effect of CS-US temporal discontiguity further highlights the importance of GlyT1-dependent mechanisms in the regulation of associative learning.
Laboratory of Behavioural Neurobiology, Swiss Federal Institute of Technology (ETH) Zurich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland; Legacy Research Institute, 1225 NE 2nd Avenue, Portland, OR 97232, United States.
Philipp
P
Singer
Laboratory of Behavioural Neurobiology, Swiss Federal Institute of Technology (ETH) Zurich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland; Legacy Research Institute, 1225 NE 2nd Avenue, Portland, OR 97232, United States.
Sylvain
S
Dubroqua
Laboratory of Behavioural Neurobiology, Swiss Federal Institute of Technology (ETH) Zurich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland; Legacy Research Institute, 1225 NE 2nd Avenue, Portland, OR 97232, United States. Electronic address: byee@downeurobiology.org.
Benjamin K
BK
Yee
D000818:Animals; D001245:Association Learning / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology*; D005239:Fear / Q000502:physiology; D005260:Female; D050487:Glycine Plasma Membrane Transport Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D016548:Prosencephalon / Q000378:metabolism*
D050487:Glycine Plasma Membrane Transport Proteins
Conditioned freezing; GlyT1; Memory; NMDA receptor; SLC6A9; Trace conditioning