Memory impairment induced by an interfering task is reverted by pre-frontal cortex lesions: A possible role for an inhibitory process in memory suppression in mice (original) (raw)
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Hippocampus, 2014
Inhibition is an important component of many cognitive functions, including memory. For example, the retrieval-induced forgetting (RIF) effect occurs when extra practice with some items from a study list inhibits the retrieval of the non-practiced items relative to a baseline condition that does not involve extra practice. Though counterintuitive, the RIF phenomenon may be important for resolving interference by inhibiting potentially competing retrieval targets. Neuroimaging studies suggest that the hippocampus and prefrontal cortex (PFC) are involved in the RIF effect, but controlled lesion studies have not yet been performed. We developed a rodent model of the RIF training procedure and trained control rats and rats with temporary inactivation of the hippocampus or mPFC. Rats were trained on a list of odor cues, presented in cups of digging medium with a buried reward, followed by additional practice trials with a subset of the cues. We then tested the rats' memories for the cues and their association with reward by presenting them with unbaited cups containing the test odorants and measuring how long they persisted in digging. Control rats exhibited a robust RIF effect in which memory for the nonpracticed odors was significantly inhibited. Thus, extra practice with some odor cues inhibited memory for the others, relative to a baseline condition that involved an identical amount of training. Inactivation of either the hippocampus or the mPFC blocked the RIF effect. We also constructed a computational model of a representational learning circuit to simulate the RIF effect. We show in this model that 'sideband suppression' of similar memory representations can reproduce the RIF effect and that alteration of the suppression parameters and learning rate can reproduce the lesion effects seen in our rats. Our results suggest that the RIF effect is widespread and that inhibitory processes are an important feature of memory function.
Behavioural Brain Research, 2010
The aim of this study was to determine if the memory of the association between a step-down response and a foot-shock can be dissociated from the memory of the context in which the shocking experience occurred. To test this, two versions of the step-down inhibitory avoidance task were used: a standard version, in which animals were given one trial with a weak exposure to the context and a new version, in which animals were given a stronger exposure to the context. A retention test was performed with the platform placed either in the same conditioning chamber as during the acquisition phase or in a new context. Our results demonstrate that the step-down inhibitory avoidance can actually be solved without a functional hippocampus. Specifically, the results show that hippocampus-lesioned mice and sham controls can express similar level of memory performance but use two different strategies which were distinguished by assessing retention in a new context. Hippocampus-lesioned mice and mice injected with forskolin (adenylyl cyclase activator) 3 h after acquisition use a memory strategy which is independent of the context of acquisition. In addition, our results confirm that the cAMP signaling pathway is a key step in memory consolidation processing.
The medial prefrontal cortex is critical for memory retrieval and resolving interference
Learning & Memory, 2013
The prefrontal cortex (PFC) is known to be critically involved in strategy switching, attentional set shifting, and inhibition of prepotent responses. A central feature of this kind of behavioral flexibility is the ability to resolve conflicting response tendencies, suggesting a general role of the PFC in resolving interference. If so, the PFC should also be involved in memory retrieval, which involves competition between potential retrieval targets. Moreover, the PFC should be needed whenever interference is high, regardless of the strategic or attentional requirements of the task. To test this hypothesis, we temporarily inactivated the mPFC with muscimol and tested rats on several olfactory learning tasks. Rats given muscimol were able to learn a few discrimination problems when they were learned one at a time. However, they were severely impaired when they had to learn and remember many odors concurrently. Rats given muscimol also suffered greater interference when learning two l...
Reconsideration of the role of the hippocampus in learned inhibition
Behavioural Brain Research, 2001
The purpose of this article is to reconsider the role of the hippocampus in learning tasks that require suppression or prevention of memories or responses. This type of learning has generally been referred to as inhibitory learning. Although early theories proposed that the hippocampus was important for inhibitory learning, these ideas have generally fallen out of favor. However, new developments in the conceptual understanding of inhibition along with recent experimental evidence require that we review these conceptual changes with regard to hippocampal function. We review three general categories of 'inhibition' that have been used with reference to hippocampal function: neural inhibition, inhibition of attention and associative or learned inhibition. We then consider recent developments in the field of animal learning that call for changes in the early conceptualizations of learned inhibition. Specifically, current findings suggest that different types of learning paradigms can yield conditioned inhibitors that are embedded in different associative structures, at least some of which can co-exist with conditioned excitation. Next we proceed to review a number of recent experiments from our laboratory as well as others that encouraged renewed interest in the role for the hippocampus in inhibitory learning. We then conclude by considering some of the implications of the idea that the hippocampus is involved with performance of conditioned responses based on cues that are concurrently embedded in inhibitory and excitatory associations.
Experimental Brain Research, 2003
Rats were trained on an inhibitory avoidance task to study the effects of post-training administration of tetrodotoxin (TTX, which temporarily inactivates neural activity) on memory consolidation. During training, independent groups of rats received either a mild foot shock (0.8 mA) or a stronger (1.0 mA) foot shock. TTX was administered bilaterally into the dorsal hippocampus immediately after training, and memory of the task was measured 48 h later. We corroborated the typical amnesic effect of intrahippocampal infusions of TTX in those rats trained with the mild-intensity foot shock. More importantly, with the stronger foot shock, the same treatment was ineffective in producing amnesia. These results suggest that, after an enhanced learning experience, other brain regions are also activated, which may compensate for the amnesic effect of TTX infusions into the hippocampus.
Placing memories in context: Hippocampal representations promote retrieval of appropriate memories
Hippocampus, 2016
Returning to a familiar context triggers retrieval of relevant memories, making memories from other contexts less likely to intrude and cause interference. We investigated the physiology that underlies the use of context to prevent interference by recording hippocampal neurons while rats learned two conflicting sets of discrimination problems, either in the same context or in two distinct contexts. Rats that learned the conflicting problem sets in the same context maintained similar neural representations, and performed poorly because conflicting memories interfered with new learning. In contrast, rats that learned in different contexts formed distinct ensemble representations and performed significantly better. We also measured trial-to-trial variation in representations and found that hippocampal activity was directly linked with performance: on trials where an old representation was active, rats were far more likely to make errors. These results show that the formation of distinc...
On the role of inhibitory control in forgetting unwanted memories: A consideration of three methods
When confronted with reminders to things that we would prefer not to think about, we often attempt to put the unwanted memories out of awareness. Here, I argue that the ability to control memory is a special case of a broad class of situations thought to require executive control: response override. In such situations, one must stop a strong habitual response to a stimulus due to situational demands, a function thought to be accomplished by inhibitory processes that suppress the response, enabling more flexible, context-sensitive control over behavior. Recent behavioral studies show that inhibitory mechanisms that control overt behavior are also targeted at declarative memories to control retrieval. Recent neuroimaging findings (Anderson et al., 2004) further establish that controlling awareness of unwanted memories is associated with increased dorsolateral prefrontal cortex activation, reduced hippocampal activation, and impaired retention of the unwanted trace and that the magnitude of activation in prefrontal cortex predicts memory suppression. These findings indicate that cognitive and neural systems that support our ability to override prepotent responses can be recruited to override declarative memory retrieval, and that this cognitive act leads to memory failure. The relation between these findings and those obtained with the directed forgetting procedure is also discussed.
2001
The purpose of this article is to reconsider the role of the hippocampus in learning tasks that require suppression or prevention of memories or responses. This type of learning has generally been referred to as inhibitory learning. Although early theories proposed that the hippocampus was important for inhibitory learning, these ideas have generally fallen out of favor. However, new developments in the conceptual understanding of inhibition along with recent experimental evidence require that we review these conceptual changes with regard to hippocampal function. We review three general categories of 'inhibition' that have been used with reference to hippocampal function: neural inhibition, inhibition of attention and associative or learned inhibition. We then consider recent developments in the field of animal learning that call for changes in the early conceptualizations of learned inhibition. Specifically, current findings suggest that different types of learning paradigms can yield conditioned inhibitors that are embedded in different associative structures, at least some of which can co-exist with conditioned excitation. Next we proceed to review a number of recent experiments from our laboratory as well as others that encouraged renewed interest in the role for the hippocampus in inhibitory learning. We then conclude by considering some of the implications of the idea that the hippocampus is involved with performance of conditioned responses based on cues that are concurrently embedded in inhibitory and excitatory associations.
Early prefrontal activation as a mechanism to prevent forgetting in the context of interference
The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2013
To determine whether activation of brain compensatory mechanisms occur during the encoding process in older people. Moreover, two different levels of interference (distraction and interruption) were presented during the maintenance period to examine how they modulate brain activity profiles. Design: A delayed match-to-sample task with two experimental conditions: distraction and interruption. Participants: Twenty-seven young adults from Complutense University of Madrid and 20 healthy older adults from Complutense Elderly University of Madrid. Measurements: Magnetoencephalography scans were recorded during the execution of a working memory interference task. Brain activity sources from younger and older adults during the encoding stage were compared in each condition using minimum norm estimation analyses. Results: The elderly showed enhancement of prefrontal activity during early latencies of the encoding process in both conditions. In the distraction condition, enhanced activity was located in left ventrolateral prefrontal regions, whereas in the interruption condition, enhanced activity was observed in the right ventral prefrontal areas and anterior cingulate cortex. Conclusion: Increased recruitment of prefrontal regions in the elderly might be related to the processing depth of information, encoding of new information and semantic associations that are successfully recalled, and with interference resolution and preparatory control when the level of interference becomes higher. These prefrontal modulations during early latencies might reflect a higher top-down control of the encoding process in normal aging to prevent forgetting. (Am J