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The postrhinal cortex (POR), the rodent homologue of the primate parahippocampal cortex (PHC), has been implicated in contextual and spatial processing. For instance, prior studies have demonstrated that permanent lesions of POR impair contextual fear conditioning. In contrast, permanent lesions of POR, specifically prior to training, do not impact auditory fear conditioning. In the current experiments, we examined the role of POR in the expression of auditory fear conditioning by using chemogenetics to silence neural activity in POR at the time of retrieval testing. Considering that extinction is context-dependent, and POR contributes to contextual memory, we hypothesized that POR would be necessary for expression of auditory fear conditioning following extinction. We found that POR inactivation during retrieval impaired freezing to an auditory cue that was tested in the conditioning context (A) after it had been extinguished in a different context (B). However, the involvement of POR was not specific to extinction. POR inactivation also impaired freezing to an auditory fear cue that had not undergone extinction. Thus, while prior studies have identified a role for POR in contextual fear conditioning, the current findings extend the functional role of POR to include the expression of auditory fear conditioning., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The retrosplenial cortex (RSC) is positioned at the interface between cortical sensory regions and the hippocampal/parahippocampal memory system. As such, it has been theorized that RSC may have a fundamental role in linking sensory stimuli together in the service of forming complex representations. To test this, three experiments were carried out to determine the effects of RSC damage or temporary inactivation on learning or performing a negative patterning discrimination. In this procedure, two conditioned stimuli are reinforced when they are presented individually (i.e., stimulus elements) but are non-reinforced when they are presented simultaneously as a compound stimulus. Normal rats successfully discriminate between the two types of trials as evidenced by more responding to the elements compared to the compound stimulus. This is thought to reflect the formation of a configural representation of the compound stimulus; that is, the two cues are linked together in such a fashion that the compound stimulus is a wholly different, unique stimulus. Permanent lesions of RSC made prior to training (Experiment 1) had no effect on learning the discrimination. However, lesions (Experiment 2) or temporary chemogenetic inactivation (Experiment 3) of RSC made after training impaired subsequent performance of the discrimination. We argue that this pattern of results indicates that RSC may normally be involved in forming the configural representations manifested in negative patterning, but that absent the RSC, other brain systems or structures can compensate sufficiently to result in normal behavior., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Although the retrosplenial cortex (RSC) is necessary for the retrieval of remotely acquired fear to a discrete auditory cue, it is not necessary for the retrieval of recently acquired cued-fear memories. Thus, the RSC's role in memory retrieval for discrete cues is time-dependent. The purpose of the current experiment was to identify the larger cortical circuit involved in the retrieval of remotely-acquired auditory fear memories. One candidate circuit involves the RSC and secondary auditory cortex; the secondary auditory cortex is also necessary for the retrieval of remotely acquired auditory fear memories (Sacco & Sacchetti, 2010), and sends direct projections to the RSC. To test this possibility, we assessed retrieval of remote memory following functional disconnection of the RSC and secondary auditory cortex. Complete disconnection of these regions produced a larger impairment in fear expression to a remotely acquired auditory cue compared to partial disconnection of these regions. These results are consistent with the notion that RSC and secondary auditory cortex form a functional circuit involved in the retrieval of remotely acquired fear to a discrete auditory cue. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

This special issue on the cognitive functions of the retrosplenial cortex highlights progress that has been made in recent years in understanding the anatomy and function of the retrosplenial cortex in both animals and humans. The articles in this issue of Behavioral Neuroscience use a number of different approaches that together provide an up-to-date account of recent progress in understanding how the retrosplenial cortex contributes to cognition, with an emphasis on its functional role in spatial navigation and learning and memory. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Although the retrosplenial cortex (RSC) is critically involved in spatial learning and memory, it appears to have more selective contributions to learning and memory for discrete cues. For example, damage to the RSC does not impair Pavlovian delay fear conditioning to a discrete auditory cue (e.g., tone), when RSC manipulation occurs just prior to, or shortly after, conditioning. In contrast, when lesions of the RSC occur following a substantial retention interval (e.g., 28 days), the RSC is necessary for retrieval of fear to the tone. Thus, the RSC makes time-dependent contributions to memory retrieval for discrete auditory cues. The purpose of the current experiment was to assess if the time-dependent involvement of the RSC in cue-specific fear memory extended to cues of other sensory modalities. Rats firsts underwent fear conditioning to a visual stimulus, and lesions of the RSC subsequently occurred 1 or 28 days later. Lesions of the RSC impaired fear expression when made 28 days after conditioning, but not when made 1 day following conditioning. Coupled with previous findings, the current results suggest the RSC is necessary for retrieval of remotely acquired cued fear memories across multiple modalities. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Extinction of fear to a Pavlovian conditioned stimulus (CS) is known to be context-specific. When the CS is tested outside the context of extinction, fear returns, or renews. Several studies have demonstrated that renewal depends upon the hippocampus, although there are also studies where renewal was not impacted by hippocampal damage, suggesting that under some conditions context encoding and/or retrieval of extinction depends upon other regions. One candidate region is the retrosplenial cortex (RSC), which is known to contribute to contextual and spatial learning and memory. Using a conditioned-suppression paradigm, Experiment 1 tested the impact of pre-training RSC lesions on renewal of extinguished fear. Consistent with previous studies, lesions of the RSC did not impact acquisition or extinction of conditioned fear to the CS. Further, there was no evidence that RSC lesions impaired renewal, indicating that contextual encoding and/or retrieval of extinction does not depend upon the RSC. In Experiment 2, post-extinction lesions of either the RSC or dorsal hippocampus (DH) also had no impact on renewal. However, in Experiment 3, both RSC and DH lesions did impair performance in an object-in-place procedure, an index of place memory. RSC and DH contributions to extinction and renewal are discussed., (Copyright © 2016 Elsevier B.V. All rights reserved.)

It has been suggested that contextual fear conditioning can be supported by either an elemental system, where individual features of the environment are associated with shock, or a configural system, where environmental features are bound together and associated with shock. Although the retrosplenial cortex (RSC) is known to be involved in contextual fear conditioning, it is not clear whether it contributes to the elemental or configural system. To isolate the role of the RSC in contextual fear conditioning, the current experiments examined the influence of RSC lesions on the context preexposure facilitation effect, a procedure known to produce conditioning to a configural representation of context. In Experiment 1, rats that were preexposed to the conditioning context froze more compared to rats that were not, replicating the context preexposure facilitation effect. Although pretraining lesions of the RSC had no impact on the context preexposure facilitation effect (Experiment 2a), posttraining lesions attenuated the effect (Experiment 2b), suggesting that the RSC normally contributes to a configural context representation. Retrohippocampal contributions to contextual fear conditioning are discussed. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

The restrosplenial cortex (RSC) has a well-established role in contextual and spatial learning and memory, consistent with its known connectivity with visuo-spatial association areas. In contrast, RSC appears to have little involvement with delay fear conditioning to an auditory cue. However, all previous studies have examined the contribution of the RSC to recently acquired auditory fear memories. Since neocortical regions have been implicated in the permanent storage of remote memories, we examined the contribution of the RSC to remotely acquired auditory fear memories. In Experiment 1, retrieval of a remotely acquired auditory fear memory was impaired when permanent lesions (either electrolytic or neurotoxic) were made several weeks after initial conditioning. In Experiment 2, using a chemogenetic approach, we observed impairments in the retrieval of remote memory for an auditory cue when the RSC was temporarily inactivated during testing. In Experiment 3, after injection of a retrograde tracer into the RSC, we observed labeled cells in primary and secondary auditory cortices, as well as the claustrum, indicating that the RSC receives direct projections from auditory regions. Overall our results indicate the RSC has a critical role in the retrieval of remotely acquired auditory fear memories, and we suggest this is related to the quality of the memory, with less precise memories being RSC dependent., (© 2016 Todd et al.; Published by Cold Spring Harbor Laboratory Press.)

The retrosplenial cortex (RSC) has an important role in contextual learning and memory. While the majority of experiments have focused on the physical context, the present study asked whether the RSC is involved in processing the temporal context. Rats were trained in a temporal discrimination procedure where the duration of the intertrial interval (ITI) signaled whether or not the next tone conditioned stimulus would be paired with food pellet reinforcement. When the tone was presented after a 16-min ITI it was reinforced, but when it was presented after a 4-min ITI it was not. Rats demonstrated successful discrimination in this procedure by responding more to the tone on reinforced trials than on non-reinforced trials. Pre-training electrolytic lesions of the RSC attenuated acquisition of the temporal discrimination. The results are the first to demonstrate a role for the RSC in processing temporal information and in turn extend the role of the RSC beyond the physical context to now include the temporal context., (© 2014 Wiley Periodicals, Inc.)

The retrosplenial cortex (RSC) is reciprocally connected with the hippocampus and various parahippocampal cortical regions, suggesting that RSC is well-positioned to contribute to hippocampal-dependent memory. Consistent with this, substantial behavioral evidence indicates that RSC is essential for consolidating and/or retrieving contextual and spatial memories. In addition, there is growing evidence that RSC neurons undergo activity-dependent plastic changes during memory formation and retrieval. In this paper we review both the behavioral and cellular/molecular data and posit that the RSC has a particularly important role in the storage and retrieval of spatial and contextual memories perhaps due its involvement in binding together multiple cues in the environment. We identify remaining questions and avenues for future research that take advantage of emerging methods to selectively manipulate RSC neurons both spatially and temporally and to image the RSC in awake, behaving animals.

An essential aspect of episodic memory is the formation of associations between neutral sensory cues in the environment. In light of recent evidence that this critical aspect of learning does not require the hippocampus, we tested the involvement of the retrosplenial cortex (RSC) in this process using a chemogenetic approach that allowed us to temporarily silence neurons along the entire rostrocaudal extent of the RSC. A viral vector containing the gene for a synthetic inhibitory G-protein-coupled receptor (hM4Di) was infused into RSC. When the receptor was later activated by systemic injection of clozapine-N-oxide, neural activity in RSC was transiently silenced (confirmed using a patch-clamp procedure). Rats expressing hM4Di and control rats were trained in a sensory preconditioning procedure in which a tone and light were paired on some trials and a white noise stimulus was presented alone on the other trials during the Preconditioning phase. Thus, rats were given the opportunity to form an association between a tone and a light in the absence of reinforcement. Later, the light was paired with food. During the test phase when the auditory cues were presented alone, controls exhibited more conditioned responding during presentation of the tone compared with the white noise reflecting the prior formation of a tone-light association. Silencing RSC neurons during the Preconditioning phase prevented the formation of an association between the tone and light and eliminated the sensory preconditioning effect. These findings indicate that RSC may contribute to episodic memory formation by linking essential sensory stimuli during learning., (Copyright © 2014 the authors 0270-6474/14/3410982-07$15.00/0.)

The retrosplenial cortex (RSP) and postrhinal cortex (POR) are heavily interconnected with medial temporal lobe structures involved in learning and memory. Previous studies indicate that RSP and POR are necessary for contextual fear conditioning, but it remains unclear whether these regions contribute individually or instead work together as a functional circuit to modulate learning and/or memory. In Experiment 1, learning-related neuronal activity was assessed in RSP from home cage, shock-only, context-only, or fear-conditioned rats using real-time PCR and immunohistochemical methods to quantify immediate-early gene expression. A significant increase in activity-regulated cytoskeleton-associated protein (Arc) mRNA and Arc and c-Fos protein expression was detected in RSP from fear-conditioned rats compared with all other groups. In Experiment 2, retrograde tracing combined with immunohistochemistry revealed that, compared with controls, a significant proportion of cells projecting from RSP to POR were immunopositive for c-Fos in fear-conditioned rats. These results demonstrate that neurons projecting from RSP to POR are indeed active during fear conditioning. In Experiment 3, a functional disconnection paradigm was used to further examine the interaction between RSP and POR during fear conditioning. Compared with controls, rats with unilateral lesions of RSP and POR on opposite sides of the brain exhibited impaired contextual fear memory, whereas rats with unilateral lesions in the same hemisphere displayed intermediate levels of freezing compared with controls and rats with contralateral lesions. Collectively, these results are the first to show that RSP and POR function as a cortical network necessary for contextual fear learning and memory.

The retrosplenial cortex (RSP) is highly interconnected with medial temporal lobe structures, yet relatively little is known about its specific contributions to learning and memory. One possibility is that RSP is involved in forming associations between multiple sensory stimuli. Indeed, damage to RSP disrupts learning about spatial or contextual cues and also impairs learning about co-occurring conditioned stimuli (CSs). Two experiments were conducted to test this notion more rigorously. In Experiment 1, rats were trained in a serial feature negative discrimination task consisting of reinforced presentations of a tone alone and nonreinforced serial presentations of a light followed by the tone. Thus, in contrast to prior studies, this paradigm involved serial presentation of conditioned stimuli (CS), rather than simultaneous presentation. Rats with damage to RSP failed to acquire the discrimination, indicating that RSP is required for forming associations between sensory stimuli regardless of whether they occur serially or simultaneously. In Experiment 2, a sensory preconditioning task was used to determine if RSP was necessary for forming associations between stimuli even in the absence of reinforcement. During the first phase of this procedure, one auditory stimulus was paired with a light while a second auditory stimulus was presented alone. In the next phase of training, the same light was paired with food. During the final phase of the procedure both auditory stimuli were presented alone during a single session. Control, but not RSP-lesioned rats, exhibited more food cup behavior following presentation of the auditory cue that was previously paired with light compared with the unpaired auditory stimulus, indicating that a stimulus-stimulus association was formed during the first phase of training. These results support the idea that RSP has a fundamental role in forming associations between environmental stimuli., ((PsycINFO Database Record (c) 2011 APA, all rights reserved).)

Physical exercise induces widespread neurobiological adaptations and improves learning and memory. Most research in this field has focused on hippocampus-based spatial tasks and changes in brain-derived neurotrophic factor (BDNF) as a putative substrate underlying exercise-induced cognitive improvements. Chronic exercise can also be anxiolytic and causes adaptive changes in stress-reactivity. The present study employed a perirhinal cortex-dependent object recognition task as well as the elevated plus maze to directly test for interactions between the cognitive and anxiolytic effects of exercise in male Long Evans rats. Hippocampal and perirhinal cortex tissue was collected to determine whether the relationship between BDNF and cognitive performance extends to this non-spatial and non-hippocampal-dependent task. We also examined whether the cognitive improvements persisted once the exercise regimen was terminated. Our data indicate that 4weeks of voluntary exercise every-other-day improved object recognition memory. Importantly, BDNF expression in the perirhinal cortex of exercising rats was strongly correlated with object recognition memory. Exercise also decreased anxiety-like behavior, however there was no evidence to support a relationship between anxiety-like behavior and performance on the novel object recognition task. There was a trend for a negative relationship between anxiety-like behavior and hippocampal BDNF. Neither the cognitive improvements nor the relationship between cognitive function and perirhinal BDNF levels persisted after 2weeks of inactivity. These are the first data demonstrating that region-specific changes in BDNF protein levels are correlated with exercise-induced improvements in non-spatial memory, mediated by structures outside the hippocampus and are consistent with the theory that, with regard to object recognition, the anxiolytic and cognitive effects of exercise may be mediated through separable mechanisms., (Copyright 2010 Elsevier Inc. All rights reserved.)

Mounting evidence indicates that the retrosplenial cortex (RSP) has a critical role in spatial navigation. The goal of the present study was to characterize the specific nature of spatial memory deficits that are observed following damage to RSP. Rats with RSP lesions or sham lesions were first trained in a working memory task using an 8-arm radial arm maze. Rats were allowed 5min to visit each arm and retrieve food pellets and a 5-s delay was imposed between arm choices. Consistent with previous research, rats with RSP damage committed more errors than controls. In particular, RSP-lesioned rats committed more errors of omission (failing to visit an arm of the maze), but there were no lesion effects on errors of commission (revisiting an arm). Neither group of rats exhibited a turn bias (i.e., always turning a certain direction when choosing an arm). At the end of the training phase of the experiment, both groups had reached asymptote and committed very few errors. In the subsequent test phase, a longer delay (30-s) was imposed during some sessions. Both control and RSP-lesioned rats continued to make few errors during sessions with the standard 5-s delay, but RSP-lesioned rats were impaired at the 30-s delay and committed more errors of commission, consistent with an increase in taxing spatial working memory.

The authors used an associative learning paradigm to assess the effects of perirhinal or postrhinal damage on attentional orienting. Control rats and rats with lesions of either the perirhinal or postrhinal cortex initially displayed high levels of orienting behavior (rearing) to presentations of a light cue. Continued nonreinforced presentations resulted in normal habituation of the response. In addition, orienting reemerged in control rats, indicating increased attentional processing of the cue. This conditioned orienting did not reemerge in rats with either perirhinal or postrhinal lesions, providing direct evidence that the rat perirhinal and postrhinal cortices each play a role in attention. These results are consistent with an emerging view that some structures within the medial temporal lobe have nonmnemonic functions., (Copyright 2004 APA.)

Spatial and contextual learning are considered to be dependent on the hippocampus, but the extent to which other structures in the medial temporal lobe memory system support these functions is not well understood. This study examined the effects of individual and combined lesions of the perirhinal, postrhinal, and entorhinal cortices on spatial and contextual learning. Lesioned subjects were consistently impaired on measures of contextual fear learning and consistently unimpaired on spatial learning in the Morris water maze. Neurotoxic lesions of perirhinal or postrhinal cortex that were previously shown to impair contextual fear conditioning (Bucci et al., 2000) or contextual discrimination (Bucci et al., 2002) caused little or no impairment in place learning and incidental learning in the water maze. Combined lesions of perirhinal plus lateral entorhinal or postrhinal plus medial entorhinal cortices resulted in deficits in acquisition of contextual discrimination but had no effect on place learning in the water maze. Finally, a parahippocampal lesion comprising combined neurotoxic damage to perirhinal, postrhinal, and entorhinal cortices resulted in profound impairment in acquisition of a standard passive avoidance task but failed to impair place learning. In the same experiment, rats with hippocampal lesions were impaired in spatial navigation. These results indicate that tasks requiring the association between context and an aversive stimulus depend on corticohippocampal circuitry, whereas place learning in the water maze can be accomplished without the full complement of highly processed information from the cortical regions surrounding the hippocampus. The evidence that different brain systems underlie spatial navigation and contextual learning has implications for research on memory when parahippocampal regions are involved.

The posterior parietal cortex (PPC) is a component of a major cortico-hippocampal circuit that is involved in relational learning, yet the specific contribution of PPC to hippocampal-dependent learning is unresolved. To address this, two experiments were carried out to test the effects of PPC damage on tasks that involve forming associations between multiple sensory stimuli. In Experiment 1, sham or electrolytic lesions of the PPC were made before rats were tested on a three-phase sensory preconditioning task. During the first phase, half of the training trials consisted of pairings of an auditory stimulus followed by a light. During the other trials, a second auditory stimulus was presented alone. In the next phase of training, the same light was paired with food, but no auditory stimuli were presented. During the final phase of the procedure both auditory stimuli were presented in the absence of reinforcement during a single test session. As is typically observed during the test session, control rats exhibited greater conditioned responding to the auditory cue that was previously paired with light compared to the unpaired cue. In contrast, PPC-lesioned rats responded equally to both auditory cues. In Experiment 2, PPC-lesioned and control rats were trained in a compound feature negative discrimination task consisting of reinforced presentations of a tone-alone and non-reinforced simultaneous presentations of a light-tone compound stimulus. Control rats but not rats with damage to the PPC successfully learned the discrimination. Collectively, these results support the idea that the PPC contributes to relational learning involving multimodal sensory stimuli, perhaps by regulating the attentional processing of conditioned stimuli [ABSTRACT FROM AUTHOR]

Abstract: The posterior parietal cortex (PPC) of rats has most recently been defined based on patterns of thalamic and cortical connectivity. The anatomical characteristics of this area suggest that it may be homologous to the PPC of primates and contribute to similar functions. This review summarizes evidence for and against a role for the rat PPC in attention and working memory and evaluates how the function of the rat PPC compares to that of primates on these dimensions. Theories of how the rat PPC contributes to behavior are presented, including the notion that PPC may serve as an interface between attention and learning. Finally, several avenues for future research are considered. [Copyright &y& Elsevier]

The majority of research regarding contextual learning and memory has focused on the contributions of the hippocampus and related medial temporal lobe structures. However, little is known about other possible cortical contributions to these processes. Our laboratory recently demonstrated that electrolytic lesions of the retrosplenial cortex (RSP), a posterior region of cingulate cortex, impaired contextual but not cue-specific fear conditioning. The present experiments further examined the role of RSP in contextual fear memory using fiber-sparing neurotoxic lesions and both signaled and unsignaled fear conditioning paradigms. Despite comparable acquisition of the conditioned fear response, rats with neurotoxic lesions of RSP exhibited impaired contextual memory relative to control animals in both the signaled and unsignaled paradigms. These results further suggest an important role for RSP in contextual learning and memory. [ABSTRACT FROM AUTHOR]

The retrosplenial cortex (RSP) and the posterior parietal cortex (PPC) are the primary sources of cortical sensory input to the postrhinal cortex (POR) in rodents. Together, these areas compose a major corticohippocampal circuit that is involved in processing visuospatial information. The POR has been implicated in contextual learning and memory, consistent with the type of information presumably being processed by this region. By comparison, little is known about the role of the RSP or the PPC in contextual learning. In the present study, rats were trained either before or after surgery in a standard signaled fear conditioning task in which an auditory cue was paired with foot shock. Contextual fear and tone-specific fear were assessed in subsequent test sessions. In Experiment 1, electrolytic damage to the RSP either before or immediately after training impaired the expression of contextual fear but not tone-specific fear. In contrast, electrolytic damage to the PPC had no effect on conditional fear to the context or the tone in Experiment 2. These findings indicate that the RSP, but not the PPC, contributes to the processing of contextual information by the POR corticohippocampal processing stream. [ABSTRACT FROM AUTHOR]

Features a study which examined the role of the postrhinal cortex (POR) and the perirhinal cortex (PER) in processing relational or contextual information with Pavlovian fear conditioning. Role of the operations performed on sensory information by the POR and PER; Methodology; Results and discussion.

The perirhinal (PER) and postrhinal (POR) cortices, two components of the medial temporal lobe memory system, are reciprocally connected with the hippocampus both directly and via the entorhinal cortex. Damage to PER or POR before or shortly after training on a contextual fear conditioning task causes deficits in the subsequent expression of contextual fear, implicating these regions in the acquisition or expression of contextual memory. Here, we examined the contribution of PER and POR to the processing of remotely learned contextual information. Male Long-Evans rats were trained in an unsignaled contextual fear conditioning paradigm. After training, rats received bilateral neurotoxic lesions to PER or POR or sham control surgeries at three different training-to-lesion intervals: 1,28, or 100 d after training. Two weeks after surgery, lesioned and control rats were returned to the training context to assess contextual fear as measured by freezing. Rats with PER or POR damage froze significantly less in the training context than control rats but were not different from each other. The severity of the deficit did not differ across training-to- lesion intervals for any group. This pattern of deficits differs from that of posttraining hippocampal lesions, for which longer training-to- lesion intervals produce significantly more fear-conditioned contextual freezing than shorter training-to-lesion intervals. In the absence of such a retrograde gradient in the present study, our interpretation is that PER and POR have an ongoing role in the storage or retrieval of representations for context. Alternatively, these regions may be involved in a more extended consolidation process that becomes apparent beyond 100 d after learning. [ABSTRACT FROM AUTHOR]

The article presents a study that investigates posterior parietal cortex's cognitive functions of individuals in the U.S. Results of experiments done on non-human primates reveal similar activation of cognitive functions of the posterior parietal cortex. Moreover, results of neurophysiological experiments that investigates the difference between the different cortical areas and the posterior parietal cortex are also mentioned.