Trinette Dirikx

Deficits in acquisition and extinction of conditioned responses in mGluR7 knockout mice

Metabotropic glutamate receptor 7 (mGluR7) is expressed in brain regions implicated in emotional learning and working memory, and previous behavioral experiments indicated contributions of mGluR7 to various complex behaviors. In the present study, we investigated the specific effects of mGluR7 deletion on a variety of conditioning paradigms that model crucial neurocognitive and psychopathological behavioral phenomena. Null-mutant mGluR7(-/-) mice displayed defects during scheduled appetitive conditioning, acquisition and extinction of appetitive odor conditioning, extinction of response suppression-based conditioned emotional responding (CER), acquisition of discriminative CER, and contextual fear conditioning. mGluR7(-/-) animals were slower to acquire the association between a conditioned stimulus and a positive or negative reinforcer, but eventually reached similar performance levels to their wildtype littermates. Notably, extinction learning of conditioned responses was slower in mGluR7(-/-) compared to wildtype animals. The observed delays in the acquisition of complicated stimulus associations across conditioning procedures may suggest a critical role for mGluR7 in neurocognitive functions and psychopathology.

Differential acquisition, extinction, and reinstatement of conditioned suppression in mice

In animals, the reappearance of conditioned fear responses after extinction has been primarily investigated using single-cue conditioning paradigms. However, a differential paradigm can overcome several of the disadvantages associated with a single-cue procedure. In the present study, the reinstatement phenomenon was assessed in mice using a differential conditioned suppression paradigm. In a first phase, one conditioned stimulus (CS +) was consistently paired with an unconditioned stimulus (US; footshock) while another CS (CS–) was not, resulting in selective suppression of previously trained instrumental behaviour during the CS +. After the extinction phase, half of the animals (reinstatement group) were presented with unsignalled USs, while the other half were not (control group). A differential return of conditioned responding was observed in the reinstatement group, but not in the control group. The implications of these findings for future conditioning research are discussed.

Assessing valence indirectly and online

In the present experiment, participants performed a reaction time task that was modelled after the affective priming procedure and was designed to track (changes in) the evaluative meaning of the conditioned stimuli (CSs) in a differential fear acquisition and subsequent extinction procedure indirectly and online. We asked participants to classify a visual probe that could appear during the reinforced CS and the unreinforced CS. The visual probe consisted of five positive or five negative smiley faces. Results indicated that the online task succeeded in tracing (shifts in) valence; superior performance was observed when CS and probe were congruent in affective meaning as compared to when they were incongruent. This congruency effect was not only observed at the end of the acquisition phase but also at the beginning and end of the extinction phase, which suggests that the acquired valence of the CSs survived extinction.

On what we cannot learn from proximity data

Different issues raised in the commentaries are elaborated in this reply. The focus was on the following five topics: (a) the nature of storage deficits in the patient groups and the different meanings that can be attached to it, (b) the possible explanations for the disordered responses of the patients, (c) suggestions for the use of other techniques to study semantic deficits, (d) the Warrington and Shallice criteria to distinguish between access and storage problems, and (e) some technical (statistical) issues raised in the commentaries. The reply concludes by highlighting the key findings reported in the target article that seem to be accepted by the large majority of the commentators.