Postrhinal cortex contributions to the expression of auditory fear conditioning.

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.

Examining a role for the retrosplenial cortex in age-related memory impairment.

Aging is often characterized by changes in the ability to form and accurately recall episodic memories, and this is especially evident in neuropsychiatric conditions including Alzheimer's disease and dementia. Memory impairments and cognitive decline associated with aging mirror the impairments observed following damage to the retrosplenial cortex, suggesting that this region might be important for continued cognitive function throughout the lifespan. Here, we review lines of evidence demonstrating that degeneration of the retrosplenial cortex is critically involved in age-related memory impairment and suggest that preservation of function in this region as part of a larger circuit that supports memory maintenance will decrease the deleterious effects of aging on memory processing.

Retrosplenial cortex inactivation during retrieval, but not encoding, impairs remotely acquired auditory fear conditioning in male rats.

Prior studies with permanent lesion methods have demonstrated a role for the retrosplenial cortex (RSC) in the retrieval of remotely, but not recently, acquired delay fear conditioning. To extend the generalizability of these prior findings, the present experiments used chemogenetics to temporarily inactivate the RSC during either retrieval or encoding of delay auditory fear conditioning. Inactivation of the RSC at the time of test impaired retrieval of a remotely conditioned auditory cue, but not a recently conditioned one. In addition, inactivation of the RSC during encoding had no impact on freezing during later retrieval testing for both a remotely and recently conditioned auditory cue. These findings indicate that the RSC contributes to the retrieval, but not encoding, of remotely acquired auditory fear conditioning, and suggest it has less of a role in both retrieval and encoding of recently acquired auditory fear conditioning.

Cortical Contributions to Higher-Order Conditioning: A Review of Retrosplenial Cortex Function.

In higher-order conditioning paradigms, such as sensory preconditioning or second-order conditioning, discrete (e.g., phasic) or contextual (e.g., static) stimuli can gain the ability to elicit learned responses despite never being directly paired with reinforcement. The purpose of this mini-review is to examine the neuroanatomical basis of high-order conditioning, by selectively reviewing research that has examined the role of the retrosplenial cortex (RSC) in sensory preconditioning and second-order conditioning. For both forms of higher-order conditioning, we first discuss the types of associations that may occur and then review findings from RSC lesion/inactivation experiments. These experiments demonstrate a role for the RSC in sensory preconditioning, suggesting that this cortical region might contribute to higher-order conditioning via the encoding of neutral stimulus-stimulus associations. In addition, we address knowledge gaps, avenues for future research, and consider the contribution of the RSC to higher-order conditioning in relation to related brain structures.

Reduced renewal of conditioned suppression following lesions of the dorsal hippocampus in male rats.

Extinguished responding will renew when the conditioned stimulus occurs outside the extinction context. Although studies of conditioned freezing have consistently demonstrated a role for the hippocampus in renewal, several studies have demonstrated intact renewal of conditioned suppression despite damage to the hippocampus (Frohardt, Guarraci, & Bouton, 2000; Todd, Jiang, DeAngeli, & Bucci, 2017; Wilson, Brooks, & Bouton, 1995). Because these prior studies have examined renewal when testing occurred in the original conditioning context ("Context A"), the present conditioned suppression experiments examined the role of the hippocampus when testing occurred in a context not associated with prior conditioning ("Context C"). In Experiments 1 and 2, conditioning occurred in Context A, and extinction in Context B. Renewal of conditioned suppression was observed when the extinguished conditioned stimulus (CS) was tested in Context C. However, renewal was attenuated in rats with lesions of the dorsal hippocampus (DH). Summation testing failed to detect conditioned inhibition in the extinction context, suggesting instead that the context acquired negative occasion-setting properties. Attenuated renewal was not due to an inability of DH lesioned rats to discriminate contexts (Experiment 3). These experiments thus demonstrate a role for the DH in renewal of conditioned suppression when testing occurs in a neutral context. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Retrosplenial cortex damage impairs unimodal sensory preconditioning.

The retrosplenial cortex (RSC) is positioned at the interface between cortical sensory regions and the structures that compose the medial temporal lobe memory system. It has recently been suggested that 1 functional role of the RSC involves the formation of associations between cues in the environment (stimulus-stimulus [S-S] learning; Bucci & Robinson, 2014). This suggestion is based, in part, on the finding that lesions or temporary inactivation of the RSC impair sensory preconditioning. However, all prior studies examining the role of the RSC in sensory preconditioning have used cues from multiple modalities (both visual and auditory stimuli). The purpose of the present experiment was to determine whether the RSC contributes to unimodal sensory preconditioning. In the present study we found that both electrolytic and neurotoxic lesions of the RSC impaired sensory preconditioning with auditory cues. Together with previous experiments, these findings indicate that the RSC contributes to both multisensory and unimodal sensory integration, which suggests a general role for the RSC in linking sensory cues in the environment. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Permanent damage or temporary silencing of retrosplenial cortex impairs the expression of a negative patterning discrimination.

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.

Retrosplenial cortex damage produces retrograde and anterograde context amnesia using strong fear conditioning procedures.

Contextual fear conditioning relies upon a network of cortical and subcortical structures, including the hippocampus and the retrosplenial cortex (RSC). However, the contribution of the hippocampus is parameter-dependent. For example, with "weak" training procedures, lesions of the hippocampus produce both retrograde and anterograde context amnesia. However, with "strong" training procedures (e.g., more trials and/or higher levels of footshock), lesions of the hippocampus produce retrograde context amnesia but not anterograde amnesia (Wiltgen et al., 2006). Likewise, prior studies have shown that with weak training, RSC lesions produce both retrograde and anterograde context amnesia (Keene & Bucci, 2008). The purpose of the current study was to examine the effects of RSC damage on contextual fear conditioning following strong training. In Experiment 1, lesions of the RSC resulted in both retrograde and anterograde context amnesia following strong training using the same unsignaled fear conditioning procedures described by Wiltgen et al. (2006). In Experiment 2, using a signaled fear conditioning procedure, we replicated these effects on context memory observing both retrograde and anterograde context amnesia. In contrast, there were no lesion effects on tone-fear memory. Thus, unlike lesions of the hippocampus, lesions of RSC produce both retrograde and anterograde context amnesia even when rats undergo strong fear conditioning. These findings suggest that the RSC has an essential role in contextual fear conditioning and that other systems or pathways are unable to compensate for the loss of RSC function.

Retrosplenial cortex and its role in cue-specific learning and memory.

The retrosplenial cortex (RSC) contributes to spatial navigation, as well as contextual learning and memory. However, a growing body of research suggests that the RSC also contributes to learning and memory for discrete cues, such as auditory or visual stimuli. In this review, we summarize and assess the Pavlovian and instrumental conditioning experiments that have examined the role of the RSC in cue-specific learning and memory. We use the term cue-specific to refer to these putatively non-spatial conditioning paradigms that involve discrete cues. Although these paradigms emphasize behavior related to cue presentations, we note that cue-specific learning and memory always takes place against a background of contextual stimuli. We review multiple ways by which contexts can influence responding to discrete cues and suggest that RSC contributions to cue-specific learning and memory are intimately tied to contextual learning and memory. Indeed, although the RSC is involved in several forms of cue-specific learning and memory, we suggest that many of these can be linked to processing of contextual stimuli.