Prelimbic Infralimbic Cortex Research Articles

Olfactory Information Storage Engages Subcortical and Cortical Brain Regions That Support Valence Determination.

The olfactory bulb (OB) delivers sensory information to the piriform cortex (PC) and other components of the olfactory system. OB-PC synapses have been reported to express short-lasting forms of synaptic plasticity, whereas long-term potentiation (LTP) of the anterior PC (aPC) occurs predominantly by activating inputs from the prefrontal cortex. This suggests that brain regions outside the olfactory system may contribute to olfactory information processing and storage. Here, we compared functional magnetic resonance imaging BOLD responses triggered during 20 or 100 Hz stimulation of the OB. We detected BOLD signal increases in the anterior olfactory nucleus (AON), PC and entorhinal cortex, nucleus accumbens, dorsal striatum, ventral diagonal band of Broca, prelimbic–infralimbic cortex (PrL-IL), dorsal medial prefrontal cortex, and basolateral amygdala. Significantly stronger BOLD responses occurred in the PrL-IL, PC, and AON during 100 Hz compared with 20 Hz OB stimulation. LTP in the aPC was concomitantly induced by 100 Hz stimulation. Furthermore, 100 Hz stimulation triggered significant nuclear immediate early gene expression in aPC, AON, and PrL-IL. The involvement of the PrL-IL in this process is consistent with its putative involvement in modulating behavioral responses to odor experience. Furthermore, these results indicate that OB-mediated information storage by the aPC is embedded in a connectome that supports valence evaluation.

Double dissociation and hierarchical organization of strategy switches and reversals in the rat PFC.

Prelimbic-infralimbic cortex (PL-IL) and orbitofrontal cortex (OFC) influence behavioral flexibility in the rat. The authors tested the effects of PL-IL or OFC infusion with the GABA agonist muscimol in the context of 2 flexible responding tasks: strategy switching and reversal. Muscimol infusion into PL-IL impaired retention of strategy switches but not reversals, whereas muscimol infusion into OFC impaired retention of reversals but not switches. However, whereas training in repeated reversals did not remove the requirement of PL-IL for switch retention (E. L. Rich & M. L. Shapiro, 2007), training in repeated switches did remove the requirement of OFC for reversal retention. Thus, activity during strategy switches was sufficient to initiate learning and remove the requirement of OFC in later reversals.

Effects of medial prefrontal cortex and dorsal striatum lesions on retrieval processes in rats

Exposure to training-related cues is known to reactivate associated memory and improves subsequent retention performance under various circumstances. The present studies investigated the neural basis of retrieval cue effects, by studying in two separate experiments, the involvement of the medial prefrontal cortex and of the dorsal striatum. Rats with lesions to the prelimbic-infralimbic cortex (PL-IL), to the anterior dorsal cingulate (ACd), and to the lateral and medial parts of the dorsal striatum (lDS and mDS) were first trained in a brightness discrimination avoidance task. One day later, rats were tested after being placed in the cueing box with either no training-related cue or with additional exposures to the light discriminative stimulus. None of the lesions affected the acquisition performance. During the retention test, control rats cued with the light in the box exhibited significantly better retention performance than those simply placed in the box, confirming our previous results. While mDS lesions did not modify effects of the retrieval cue, lDS as well as both PL-IL and ACd lesions blocked the facilitative effects of the discriminative stimulus. The present data indicate that ACd, PL-IL and lDS are involved in processes promoted by exposure to training cues, the nature of which are reviewed and discussed. This study in conjunction with previous ones suggests that retrieval cues activate several subcircuits mainly based on an amygdalo–prefrontal–striatum network. Activation of this network results in an improvement of the expression of the associated conditioned response, and may thus be viewed as increasing the efficacy of the retrieval processes.

Functional Specialization within Medial Frontal Cortex of the Anterior Cingulate for Evaluating Effort-Related Decisions

The rat medial frontal cortex (MFC) has been implicated in allowing animals to work harder to receive larger rewards. However, it is unknown what role the individual MFC regions [anterior cingulate cortex (ACC) and prelimbic-infralimbic cortex (PL-IL)] play in such decision making. To investigate this, we trained rats on a T-maze cost-benefit task with two possible courses of action, shown previously to be affected by complete MFC lesions. One response involved climbing a 30 cm barrier to obtain a large quantity of reward (high cost-high reward), whereas the other had a lower energetic demand but also a smaller reward gain (low cost-low reward). Before surgery, all animals preferred to select the high cost-high reward option. However, after excitotoxic ACC lesions, there was a complete reversal of behavior, with the ACC group selecting the low cost-low reward response on nearly every trial. In contrast, both control animals and rats with PL-IL lesions continued to choose to climb the barrier for the larger reward. When the same rats were tested on a delayed match-to-sample paradigm however, it was the PL-IL group that was significantly impaired at learning the response rule, with the performance of ACC rats being comparable with controls. This double dissociation indicates that the ACC is the important region within the MFC when evaluating how much effort to expand for a specific reward.

Excitotoxic lesions of the prelimbic‐infralimbic areas of the rodent prefrontal cortex disrupt motor preparatory processes

The medial prefrontal cortex (mPFC) is involved in a variety of cognitive and emotional processes; in rodents its implication in motor planning is less known, however. We therefore investigated how the mPFC contributes to the information processes involved in the execution of a reaction time task in rats. Subjects were trained to rapidly release a lever at the onset of a cue light, which was presented after an unpredictable period of variable duration (500, 750, 1000 and 1250 ms). Excitotoxic lesions of the whole mPFC or two mPFC subregions [e.g. the dorsal anterior cingulate and the prelimbic-infralimbic (PL-IL) areas] were achieved by intracerebral infusions of ibotenic acid (9.4 micro g/ micro L) at different volumes. Extensive mPFC lesions produced increased premature responding and disrupted motor readiness, e.g. the distribution of preparatory patterns during the variable preparatory periods. The deficits lasted for 3 weeks and could be reinstated 2 months after the lesion by varying the duration of the preparatory periods to increase time uncertainty. Furthermore, lesions restricted to the PL-IL cortex areas reproduced all the deficits of mPFC lesions, whereas pregenual anterior cingulate cortex lesions had no effect. The results emphasize a critical role of the rat PL-IL region in motor preparatory processes. Hence, discrete lesions of this area reproduce some deficits such as impairment of time estimation and disinhibitory behaviours observed in humans with frontal hypoactivity.

The Effects of Prelimbic and Infralimbic Lesions on Working Memory for Visual Objects in Rats

The present experiment investigated the effects of quinolinic acid (90 mM) lesions of the prelimbic-infralimbic cortices on working memory for visual objects and on acquisition of a visual object discrimination. In both tests a GO/NO-GO procedure was used. In the working memory task, rats were tested before and after surgery. A continuous recognition procedure was used to assess working memory, which involved successive exposure to different three-dimensional objects that could be displaced to receive a cereal reinforcement. Of the 12 object presentations/session, 4 objects were presented for a second time in which displacing the object did not result in a reinforcement. The number of trials between the first and second presentations of an object ranged from 0 to 3 (lags). Memory was assessed by the latency to displace an object during the second presentation. In the visual object discrimination, rats had successive exposure to two different objects. Displacement of one object resulted in a cereal reinforcement, while displacement of the other did not. The findings indicated that prelimbic-infralimbic lesions significantly impaired memory for visual objects across all lags. Prelimbic-infralimbic lesions did not impair acquisition of the visual object discrimination. The results suggest that the prelimbic-infralimbic areas are part of neural system important in the short-term memory for visual objects.

Effects of selective excitotoxic prefrontal lesions on acquisition of nonmatching- and matching-to-place in the T-maze in the rat: differential involvement of the prelimbic-infralimbic and anterior cingulate cortices in providing behavioural flexibility.

The present study investigated the contributions of the medial prefrontal cortex and its major subdivisions, the dorsal anterior cingulate (ACd) and prelimbic-infralimbic (PL) cortices, to spatial working memory and inhibitory control processes. In experiment 1, excitotoxic lesions centred in the ACd or PL cortex did not affect acquisition of a nonmatching-to-place task in the T-maze with a retention interval of 10 s. However, the same reinforced alternation task was impaired by larger prefrontal lesions that combined ACd and PL cortices. In experiment 2, new animals were trained on a matching-to-place task in the T-maze that uses a rule counter to the animals' innate bias to alternate spontaneously. Now, discrete lesions of both the ACd and PL cortices impaired acquisition, but in different ways. Both animals with PL and with ACd lesions perseverated by nonmatching for more sessions than the controls, but only the PL animals also showed a more general increase in perseveration reflected in a further, extended period of applying an inefficient response rule (e.g. always turn right) and a deficit at reversing from matching to nonmatching. Acquisition of the matching-to-place task was also impaired by combined lesions of ACd and PL cortices. Overall, whilst spatial working memory processes appear to remain intact in those animals with discrete prefrontal lesions, the present findings provide strong evidence for the differential involvement of the prelimbic-infralimbic and anterior cingulate regions in providing behavioural flexibility.

Functional dissociation between dorsal and ventral regions of the medial prefrontal cortex in rats

In order to investigate the respective roles of dorsal and ventral parts of the medial prefrontal cortex (mPFC) on a delayed alternation task, the acquisition of which is disrupted by large mPFC lesions (Winocur, 1991), rats with circumscribed lesions to the anterior cingulate (ACd) or the prelimbicinfralimbic (PL-IL) cortex were compared. As was predicted, ACd lesions severely impaired performance, and an analysis of the results suggests an involvement of this region in sequencing temporally ordered behavior. On the other hand, PL-IL lesions had no effect, a finding that was in contrast with previous evidence that PL-IL lesions induced delay-dependent deficits on a similar task (Delatour & Gisquet-Verrier, 1999). However, an important difference between the tasks related to the scheduling of critical delays. Whereas in the previous experiment, delay intervals were increased progressively in a block design, variable intertrial intervals were a constant feature of training in the present Experiment 1. In Experiment 2, rats with PL-IL lesions were administered Delatour and Gisquet-Verrier’s (1999) alternation task, but modified to incorporate Winocur’s (1991) variable-interval procedure that required less response adjustment. Under these conditions, the PL-IL group performed normally, as in Experiment 1. Taken together, the results provide evidence that the PL-IL cortex is implicated in processes that support attentional mechanisms and behavioral flexibility. Overall, the present results support the general hypothesis of subregionalization of mPFC functions.

Functional role of rat prelimbic-infralimbic cortices in spatial memory: evidence for their involvement in attention and behavioural flexibility

The involvement of the medial prefrontal cortex (mPFC), and more particularly the prelimbic and infralimbic cortices (PL-IL area), in spatial memory remains controversial. The present study investigates the effects of neurotoxic lesions restricted to the PL-IL area of the mPFC in rats trained in two different spatial tasks. In experiment 1, PL-IL lesioned rats showed normal acquisition of a delayed non-matching to position task. They were also able to plan their responses for a prospective strategy but were transiently disrupted when the initial delay was extended. In experiment 2, rats were trained to locate one baited box among 13 identical boxes distributed on a circular arena. Lesioned rats performed normally when trained from a single start position but were severely disrupted when four start positions were used. A probe trial showed this deficit was not due to failure to learn the goal location. The addition of a proximal cue signalling the goal box helped lesioned rats to directly open the goal box, but did not compensate for greater distances that they travelled to reach it. Results from both experiments indicate that the PL-IL area is directly involved neither in allocentric spatial representations nor prospective memory and is not specifically involved in working memory. This area seems more likely to be involved in both attentional processes and behavioural flexibility that may be important for processing information for working memory as well as for spatial memory.

Lesions of the prelimbic-infralimbic cortices in rats do not disrupt response selection processes but induce delay-dependent deficits: evidence for a role in working memory?

Effects of neurotoxic lesions of the prelimbic-infralimbic cortex (PL-IL) were examined in rats performing 2 conditional tasks. PL-IL-lesioned rats showed normal acquisition of a visuospatial conditional discrimination in a Y maze as well as a tone-light conditional discrimination in an operant chamber, indicating that the PL-IL is not necessary for response selection processes. When the working memory load was subsequently increased in the tone-light conditional discrimination, rats with PL-IL lesions showed a delay-dependent disruption of performance. This suggests a role of the PL-IL in some working memory processes. However, the present results, considered along with previous studies, suggest that the PL-IL does not seem to be directly involved in the processes necessary to maintain specific items over a delay period but rather in the planning of forthcoming behavioral responses on the basis of previously acquired information.

Differential involvement of the dorsal anterior cingulate and prelimbic-infralimbic areas of the rodent prefrontal cortex in spatial working memory.

The present study examined the effects of quinolinic acid lesions of the dorsal anterior cingulate and prelimbic-infralimbic cortices on spatial working memory and spatial discrimination using go/no-go procedures. All testing occurred in a 12-arm radial maze. In a working memory task, rats were allowed to enter 12 arms for a cereal reward. Three or 4 arms were presented for a 2nd time in a session, which did not result in a reward. In a spatial discrimination task, rats had successive access to 2 different arms. One arm always contained a reward, and the other never contained a reward. Prelimbic-infralimbic lesions impaired spatial working memory but only produced a transient spatial discrimination deficit. Dorsal anterior cingulate lesions did not induce a deficit in either task. These findings suggest that the prelimbic-infralimbic cortices, but not the anterior cingulate cortex, are important in spatial working memory.

Responses of the medial prefrontal cortex to stimulation of the amygdala in the rat: a study with laminar field potential recording

Responses generated in the prelimbic-infralimbic cortices (areas 32 and 25) by stimulation of the basolateral amygdala were studied by means of laminar field potential recordings. Based on the analysis of wave forms and depth potential profiles of the responses, three constituent responses were identified: (1) a surface-positive potential with a short onset latency (mean, 4.5 ms) and a long duration (ca. 70 ms) that reversed the polarity at a depth of 400 μm; (2) a surface-positive potential with a mean onset latency of 15 ms and a duration of 20 ms that reversed to a negative potential at a depth of 300 μm; and (3) a long-latency (ca. 20 ms) superficial-negative potential that reversed to a positive potential at depths below 400 μm. Lesion experiments ruled out the possibility that impulse traffic via the thalamic mediodorsal nucleus (MD) contributed to the responses. Amygdala stimulation also produced responses in the insular cortex, but they did not contaminate the responses in the mesial cortex. It is proposed that impulses originating from the amygdala provide excitation for cortical pyramidal cells at a short latency at deeper layers, but with considerable delays at upper and superficial layers, in the medial prefrontal cortex (mPFC).