Perirhinal cortex lesions in rats: Novelty detection and sensitivity to interference.
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ABSTRACT:
SUBMITTER: Albasser MM
PROVIDER: S-EPMC4450885 | biostudies-other | 2015 Jun
REPOSITORIES: biostudies-other
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Project description:The present study examined why perirhinal cortex lesions in rats impair the spontaneous ability to select novel objects in preference to familiar objects, when both classes of object are presented simultaneously. The study began by repeating this standard finding, using a test of delayed object recognition memory. As expected, the perirhinal cortex lesions reduced the difference in exploration times for novel vs. familiar stimuli. In contrast, the same rats with perirhinal cortex lesions appeared to perform normally when the preferential exploration of novel vs. familiar objects was tested sequentially, i.e. when each trial consisted of only novel or only familiar objects. In addition, there was no indication that the perirhinal cortex lesions reduced total levels of object exploration for novel objects, as would be predicted if the lesions caused novel stimuli to appear familiar. Together, the results show that, in the absence of perirhinal cortex tissue, rats still receive signals of object novelty, although they may fail to link that information to the appropriate object. Consequently, these rats are impaired in discriminating the source of object novelty signals, leading to deficits on simultaneous choice tests of recognition.
| S-EPMC4737320 | biostudies-other
Project description:Rats that have self-administered methamphetamine (meth) under long access, but not short access, conditions do not recognize novel objects. The perirhinal cortex is critical for novelty detection, and perirhinal metabotropic glutamate 5 receptors (mGlu5) are downregulated after long-access meth. The novel positive allosteric modulator (PAM) 1-(4-(2,4-difluorophenyl) piperazin-1-yl)-2-((4-fluorobenzyl)oxy)-ethanone, or DPFE, demonstrates improved solubility compared with other mGlu5 PAMs, thus allowing brain-site-specific pharmacological studies. Infusion of DPFE into perirhinal cortex restored novel object recognition in long-access meth rats. To investigate the impact of these cognitive enhancing effects on relapse, we tested the effects of DPFE infusions into perirhinal cortex on meth-seeking under two different test conditions. In the standard cue relapse test, perirhinal DPFE infusions did not alter meth-seeking in the presence of meth cues. However, in a novel cue relapse test, wherein animals were allowed to allocate responding between a novel cue and meth-conditioned cue, perirhinal DPFE infusions shifted the pattern of responding in long-access rats toward a profile resembling short-access rats, which respond equally for novel and meth cues. Perirhinal mGlu5 are thus a promising pharmacological target for the restoration of cognitive function in meth addicts. Targeting these receptors may also reduce relapse, particularly in situations where novel stimuli compete with conditioned stimuli for control over meth seeking.
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Project description:"Novelty-seeking" behavior describes the variability of rats' locomotor response, namely high and low responders (HR and LR respectively), when exposed to a novel environment. Novelty-seeking in the rat is considered to model "sensation-seeking" in humans, a personality trait related to substance abuse. It is assumed that HR rats and LR rats differ in their emotional reactivity because of the disparate incentive value of contextual stimulus, thus differentially interacting with their environment. However, little is known about how HR and LR rats recognize novelty arising from the environment. The present study evaluates whether phenotype may affect spontaneous, non-spatial novelty discrimination. Selectively bred HR and LR rats were submitted to the novel-object recognition test. The task involved a delay of 3h after a first encounter with an object ("old"), which had to be discriminated from a second object ("new"). Object discrimination was assessed minute-by-minute during a 3-min choice session. Amnesic effects of scopolamine (0.5mg/kg, intraperitoneal) were also analyzed. HR-bred rats showed sustained novel-object recognition throughout the 3-min choice session, whereas LR-bred rats began to discriminate between objects only in the last minute. Surprisingly, level of discrimination in scopolamine-treated HR-bred rats was significant during the first minute of the choice test and diminished thereafter, presumably because both objects became equally familiar as they were explored. Additionally, scopolamine induced changes in muscarine M(2) receptor gene expression in a phenotype-dependent manner. Because consistent object discrimination mainly arises during the first minute, these findings may reflect differential novelty detection in HR-bred respect to LR-bred rats.
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Project description:The lateral prefrontal cortex is known for its contribution to working memory (WM) processes in both humans and animals. Yet, recent studies indicate that the prefrontal cortex is part of a broader network of interconnected brain areas involved in WM. Within the medial temporal lobe (MTL) structures, the perirhinal cortex, which has extensive direct interactions with the lateral and orbital prefrontal cortex, is required to form active/flexible representations of familiar objects. However, its participation in WM processes has not be fully explored. The goal of this study was to assess the effects of neonatal perirhinal lesions on maintenance and monitoring WM processes. As adults, animals with neonatal perirhinal lesions and their matched controls were tested in three object-based (non-spatial) WM tasks that tapped different WM processing domains, e.g., maintenance only (Session-unique Delayed-nonmatching-to Sample, SU-DNMS), and maintenance and monitoring (Object-Self-Order, OBJ-SO; Serial Order Memory Task, SOMT). Neonatal perirhinal lesions transiently impaired the acquisition of SU-DNMS at a short (5 s) delay, but not when re-tested with a longer delay (30 s). The same neonatal lesions severely impacted acquisition of OBJ-SO task, and the impairment was characterized by a sharp increase in perseverative errors. By contrast, neonatal perirhinal lesion spared the ability to monitor the temporal order of items in WM as measured by the SOMT. Contrary to the SU-DNMS and OBJ-SO, which re-use the same stimuli across trials and thus produce proactive interference, the SOMT uses novel objects on each trial and is devoid of interference. Therefore, the impairment of monkeys with neonatal perirhinal lesions on SU-DNMS and OBJ-SO tasks is likely to be caused by an inability to solve working memory tasks with high proactive interference. The sparing of performance on the SOMT demonstrates that neonatal perirhinal lesions do not alter working memory processes per se but rather impact processes modulating impulse control and/or behavioral flexibility.
| S-EPMC4700260 | biostudies-literature
Project description:The perirhinal cortex (PRC) is a medial temporal lobe (MTL) structure known to be involved in assessing whether an object is familiar (i.e., meaningful) or novel. Recent evidence shows that the PRC is sensitive to the familiarity of both whole object configurations and their parts, and suggests the PRC may modulate part familiarity responses in V2. Here, using functional magnetic resonance imaging (fMRI), we investigated age-related decline in the PRC's sensitivity to part/configuration familiarity and assessed its functional connectivity to visual cortex in young and older adults. Participants categorized peripherally presented silhouettes as familiar ("real-world") or novel. Part/configuration familiarity was manipulated via three silhouette configurations: Familiar (parts/configurations familiar), Control Novel (parts/configurations novel), and Part-Rearranged Novel (parts familiar, configurations novel). "Real-world" judgments were less accurate than "novel" judgments, although accuracy did not differ between age groups. The fMRI data revealed differential neural activity, however: In young adults, a linear pattern of activation was observed in left hemisphere (LH) PRC, with Familiar > Control Novel > Part-Rearranged Novel. Older adults did not show this pattern, indicating age-related decline in the PRC's sensitivity to part/configuration familiarity. A functional connectivity analysis revealed a significant coupling between the PRC and V2 in the LH in young adults only. Older adults showed a linear pattern of activation in the temporopolar cortex (TPC), but no evidence of TPC-V2 connectivity. This is the first study to demonstrate age-related decline in the PRC's representations of part/configuration familiarity and its covariance with visual cortex.
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Project description:Visual recognition memory is subserved by a distributed set of neural circuits, which include structures of the temporal lobe. Conflicting experimental results regarding the role of the hippocampus in nonspatial forms of such memories have been attributed to species, task, and lesion discrepancies. We have overcome obstacles that have prevented a direct evaluation of the role of the hippocampus in this type of memory by developing for rats a nonspatial, picture-based, trial-unique, delayed matching-to-sample task that is a procedural analogue of standard visual recognition memory tasks used in primates. With this task, we demonstrate that rats have a visual memory profile, which is analogous to that in primates and depends on the function of perirhinal cortex. We also find that selective lesions of hippocampus impair delay-dependent visual memory with a profile different from that produced by damage to the perirhinal cortex. These data demonstrate that rats have a visual recognition memory system fundamentally similar to primates that depends on the function of the hippocampus.
| S-EPMC387374 | biostudies-literature
Project description:Exposure to methamphetamine (meth) can produce lasting memory impairments in humans and rodents. We recently demonstrated that extended access meth self-administration results in novel object recognition (NOR) memory deficits in rats. Recognition of novelty depends upon intact perirhinal (pRh) cortex function, which is compromised by meth-induced downregulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors. NMDA receptors containing this subunit have a critical role in pRh long-term depression (LTD), one of the primary physiological processes thought to underlie object recognition memory. We hypothesized that meth-induced downregulation of GluN2B receptors would compromise pRh LTD, leading to loss of NOR memory. We found that meth self-administration resulted in an inability to induce pRh LTD following 1 Hz stimulation, an effect that was reversed with bath application of the NMDA receptor partial agonist D-cycloserine (DCS). In addition, pRh microinfusion of DCS restored meth-induced memory deficits. Furthermore, blockade of GluN2B-containing NMDA receptors with Ro 25-6981 prevented DCS restoration of pRh LTD in meth subjects. Thus, targeting pRh LTD may be a promising strategy to treat meth-induced cognitive impairment.
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Project description:Our brain disambiguates the objects in our cluttered visual world seemingly effortlessly, enabling us to understand their significance and to act appropriately. The role of anteromedial temporal structures in this process, particularly the perirhinal cortex, is highly controversial. In some accounts, the perirhinal cortex is necessary for differentiating between perceptually and semantically confusable objects. Other models claim that the perirhinal cortex neither disambiguates perceptually confusable objects nor plays a unique role in semantic processing. One major hurdle to resolving this central debate is the fact that brain damage in human patients typically encompasses large portions of the anteromedial temporal lobe, such that the identification of individual substructures and precise neuroanatomical locus of the functional impairments has been difficult. We tested these competing accounts in patients with Alzheimer's disease with varying degrees of atrophy in anteromedial structures, including the perirhinal cortex. To assess the functional contribution of each anteromedial temporal region separately, we used a detailed region of interest approach. From each participant, we obtained magnetic resonance imaging scans and behavioural data from a picture naming task that contrasted naming performance with living and non-living things as a way of manipulating perceptual and semantic confusability; living things are more similar to one another than non-living things, which have more distinctive features. We manually traced neuroanatomical regions of interest on native-space cortical surface reconstructions to obtain mean thickness estimates for the lateral and medial perirhinal cortex and entorhinal cortex. Mean cortical thickness in each region of interest, and hippocampal volume, were submitted to regression analyses predicting naming performance. Importantly, atrophy of the medial perirhinal cortex, but not lateral perirhinal cortex, entorhinal cortex or hippocampus, significantly predicted naming performance on living relative to non-living things. These findings indicate that one specific anteromedial temporal lobe region-the medial perirhinal cortex-is necessary for the disambiguation of perceptually and semantically confusable objects. Taken together, these results support a hierarchical account of object processing, whereby the perirhinal cortex at the apex of the ventral object processing system is required to bind properties of not just perceptually, but also semantically confusable objects together, enabling their disambiguation from other similar objects and thus comprehension. Significantly, this model combining a hierarchical object processing architecture with a semantic feature statistic account explains why category-specific semantic impairments for living things are associated with anteromedial temporal lobe damage, and pinpoints the root of this syndrome to perirhinal cortex damage.
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Project description:The hippocampus is well-known to be critical for trace fear conditioning, but nothing is known about the importance of perirhinal cortex (PR), which has reciprocal connections with hippocampus. PR damage severely impairs delay fear conditioning to ultrasonic vocalizations (USVs) and discontinuous tones (pips), but has no effect on delay conditioning to continuous tones. Here we demonstrate that trace auditory fear conditioning also critically depends on PR function. The trace interval between the CS offset and the US onset was 16s. Pre-training neurotoxic lesions were produced through multiple injections of N-methyl-D-aspartate along the full length of PR, which was directly visualized during the injections. Control animals received injections with phosphate-buffered saline. Three-dimensional reconstructions of the lesion volumes demonstrated that the neurotoxic damage was well-localized to PR and included most of its anterior-posterior extent. Automated video analysis quantified freezing behavior, which served as the conditional response. PR-damaged rats were profoundly impaired in trace conditioning to either of three different CSs (a USV, tone pips, and a continuous tone) as well as conditioning to the training context. Within both the lesion and control groups, the type of cue had no effect on the mean CR. The overall PR lesion effect size was 2.7 for cue conditioning and 3.9 for context conditioning. We suggest that the role of PR in trace fear conditioning may be distinct from some of its more perceptual functions. The results further define the essential circuitry underlying trace fear conditioning to auditory cues.
| S-EPMC2629995 | biostudies-literature
Project description:Knowledge of objects in the world is stored in our brains as rich, multimodal representations. Because the neural pathways that process this diverse sensory information are largely anatomically distinct, a fundamental challenge to cognitive neuroscience is to explain how the brain binds the different sensory features that comprise an object to form meaningful, multimodal object representations. Studies with nonhuman primates suggest that a structure at the culmination of the object recognition system (the perirhinal cortex) performs this critical function. In contrast, human neuroimaging studies implicate the posterior superior temporal sulcus (pSTS). The results of the functional MRI study reported here resolve this apparent discrepancy by demonstrating that both pSTS and the perirhinal cortex contribute to crossmodal binding in humans, but in different ways. Significantly, only perirhinal cortex activity is modulated by meaning variables (e.g., semantic congruency and semantic category), suggesting that these two regions play complementary functional roles, with pSTS acting as a presemantic, heteromodal region for crossmodal perceptual features, and perirhinal cortex integrating these features into higher-level conceptual representations. This interpretation is supported by the results of our behavioral study: Patients with lesions, including the perirhinal cortex, but not patients with damage restricted to frontal cortex, were impaired on the same crossmodal integration task, and their performance was significantly influenced by the same semantic factors, mirroring the functional MRI findings. These results integrate nonhuman and human primate research by providing converging evidence that human perirhinal cortex is also critically involved in processing meaningful aspects of multimodal object representations.
| S-EPMC1461402 | biostudies-literature