Lesions to the ventral, but not the dorsal, medial prefrontal cortex enhance latent inhibition

Abstract

The acquisition of a conditioned response to a stimulus when it is paired with a reinforcer is retarded if the stimulus has previously been repeatedly pre-exposed in the absence of the reinforcer. This effect, called latent inhibition, has previously been found to be insensitive to lesions of the medial prefrontal cortex (mPFC) in rats. Using an on-baseline conditioned emotional response procedure, which is especially sensitive to small variations in the absolute magnitude of latent inhibition, we found increased latent inhibition following excitotoxic lesions of the mPFC (Experiment 1) or the ventral mPFC alone (Experiment 2) as compared with sham-operated control rats. Lesions restricted to the dorsal mPFC, however, were without effect (Experiment 2). These results are consistent with those of experiments employing another type of interference procedure, extinction. Together, these findings suggest that when different contingencies between a stimulus and a reinforcer are established in separate learning phases, lesions to the ventral mPFC result in increased interference between first-learned and second-learned contingencies. As a consequence, retrieval of the second-learned contingency is impaired, and performance is dominated by the first-learned contingency. These findings are discussed in light of the use of latent inhibition to model cognitive deficits in schizophrenia.

Early Prefrontal Functional Blockade in Rats Results in Schizophrenia-Related Anomalies in Behavior and Dopamine

“…These data could be interpreted to mean the prelimbic/ infralimbic subregion of the PFC is involved in the latent inhibition phenomenon, which would be consistent with recent studies carried out with focal lesions in adults (George et al, 2010;Nelson et al, 2010), rather than previous works performed with more dorsal lesioning sites in the anteromedian PFC (Lacroix et al, 2000;Schiller and Weiner, 2004). However, lesions in the prelimbic/infralimbic subregion of the PFC in adults resulted in enhanced latent inhibition (George et al, 2010;Nelson et al, 2010), whereas what we observed was that latent inhibition disappeared after postnatal TTX microinjection in the same PFC subregion, suggesting that different mechanisms are involved after intervention in adults and during the postnatal developmental period. The disappearance of the behavioral expression of latent inhibition obtained after neonatal TTX blockade of the PFC is similar to that observed after an identical blockade of the entorhinal cortex or ventral subiculum (Peterschmitt et al, 2007;Meyer et al, 2009;Meyer and Louilot, 2011).…”

Estrogen receptors in the central nervous system and their implication for dopamine-dependent cognition in females

“…Latent inhibition, a measure of selective attention, is dependent on dopamine transmission within the mesocorticolimbic pathway. Lesions and local infusion of a dopamine antagonist in the PFC enhance latent inhibition (Broersen et al 1996, George et al 2010) whereas lesions of the NAc or hippocampus abolish latent inhibition (Gal et al 1997, Kaye and Pearce,1987, Oswald et al, 2002). Moreover, dopaminergic activity in the anterior STR is positively correlated with behaviour in a latent inhibition task (Jeanblanc et al 2003).…”

From attention to memory along the dorsal-ventral axis of the medial prefrontal cortex: some methodological considerations

“…The functional heterogeneity of mPFC also needs to be taken into account and lesions restricted to IL mPFC have more recently been reported to potentiate latent inhibition (George et al, 2010). This study used 30 stimulus pre-exposures in a within-subject aversive on-the-baseline procedure, under which experimental conditions enhanced latent inhibition was demonstrated in a group with excitotoxic lesions restricted to IL mPFC but not PL mPFC.…”

“…The serial reaction time task measures early attentional processing and a key role for mPFC has been established using excitotoxic lesion approaches (Passetti et al, 2002; Pezze et al, 2009). Studies using excitotoxic lesions have also been conducted to examine the role of mPFC in latent inhibition (Lacroix et al, 1998, 2000b; Schiller and Weiner, 2004; George et al, 2010). Earlier studies of trace conditioning used aspiration (Kronforst-Collins and Disterhoft, 1998; Weible et al, 2000) and electrolytic lesions (McLaughlin et al, 2002; Runyan et al, 2004), both of which methods also destroy fibers of passage.…”