Recollection‐related hippocampal activity during continuous recognition: A high‐resolution fMRI study

We used high‐resolution functional magnetic resonance imaging to investigate whether successful recollection during continuous recognition is associated with relative enhancement of hippocampal activity, consistent with prior findings from experiments employing separate study and test phases. While being scanned, subjects discriminated between new and repeated pictures. Each picture, which was repeated once after an interval of between 10 and 30 items, was surrounded by a frame that was colored gray, blue, or orange. When an item repeated, its frame color determined the correct response. Repeated items surrounded by a gray frame always required an “old” judgment. A repeated item surrounded by a blue or an orange frame required a different response depending whether it was represented in the same (Target) or a different (Nontarget) color from the first presentation. Consistent with the results from previous continuous recognition experiments, robust new > old effects were found in bilateral hippocampus. In addition, an across‐subjects correlational analysis identified a cluster of voxels in right hippocampus where recollection‐related activity (operationalized by the contrast between correctly vs. incorrectly judged Nontargets) was positively correlated with recollection performance. Thus, successful recollection during continuous recognition is associated with a relative enhancement of hippocampal activity. © 2010 Wiley‐Liss, Inc.     

The human perirhinal cortex and recognition memory

The importance of the perirhinal cortex for visual recognition memory performance is undisputed. However, it has not been clear whether its contribution to performance is mainly perceptual, or mainly mnemonic, or whether the perirhinal cortex contributes to both perception and memory. We determined the effects of medial temporal lobe damage that includes complete damage to the perirhinal cortex in two amnesic patients by assessing recognition memory for complex visual stimuli across delays from 0 to 40 s. These patients, as well as six other amnesic patients with damage limited to the hippocampal formation or diencephalic structures, exhibited intact recognition memory at delays of 0–2 s and a delay-dependent memory impairment at delays of 6 s and longer. Additionally, the patients with damage to the perirhinal cortex performed worse than the other amnesic patients at delays of 25 s and longer. The findings suggest that the perirhinal cortex is not important for visual perception or immediate memory. In this respect, the findings for perirhinal cortex resemble the findings for other medial temporal lobe structures, including the hippocampus. Hippocampus 1998;8:330–339. © 1998 Wiley-Liss, Inc.     

The retrieval of learned sequences engages the hippocampus: Evidence from fMRI

Computational models suggest that the hippocampus plays an important role in the retrieval of sequences. However, empirical evidence supporting hippocampal involvement during sequence retrieval is lacking. The current study used functional magnetic resonance imaging (fMRI) to examine the role of the human hippocampus during the learning and retrieval of sequences. Participants were asked to learn four sequences comprised of six faces each. An overlapping condition, where sequences shared common elements, was comprised of two sequences in which two identical faces were shown as the middle images of both sequences. A nonoverlapping condition contained two sequences that did not share any faces between them. A third random condition contained two sets of six faces that were always presented in a random order. The fMRI data were split into a learning phase and an experienced phase based upon each individual's behavioral performance. Patterns of hippocampal activity during presentation, delay, and choice periods were assessed both during learning (learning phase) and after subjects learned the sequences to criteria (experienced phase). The results revealed hippocampal activation during sequence learning, consistent with previous findings in rats and humans. Critically, the current results revealed hippocampal activation during the retrieval of learned sequences. No difference in hippocampal activation was seen between the overlapping and nonoverlapping sequences during either sequence learning or retrieval of sequences. The results extend our current knowledge by providing evidence that the hippocampus is active during the retrieval of learned sequences, consistent with current computational models of sequence learning and retrieval. © 2009 Wiley‐Liss, Inc.     

Dissociable neural responses in the hippocampus to the retrieval of facial identity and emotion: an event-related fMRI study

In studies with brain-damaged patients and experimental animals, the medial temporal lobe, including the hippocampus and parahippocampal gyrus, has been found to play a critical role in establishing declarative or episodic memory. We measured the neural response in these structures, using event-related functional magnetic resonance imaging, while six healthy subjects performed the retrieval task for facial identity and emotion, respectively. Under the identity condition, the subjects participated in a yes/no recognition test for neutral faces learned before the scanning. Under the emotion condition, the subjects learned the faces with positive or negative expression and retrieved their expressions from neutral cue faces. The results showed that the left hippocampus is primarily involved in the identification of learned faces, and that the adjacent parahippocampal gyrus responds more to target than to distracter events. These results indicate a specific engagement of the left hippocampal regions in conscious recollection and identification of physiognomic facial features. The activity in the right hippocampus increased under both the identity and emotion conditions. The present results may relate with the functional model of face recognition in which the left hemisphere contributes to the processing of detailed features and the right hemisphere is efficient in the processing of global features.     

High-resolution fMRI investigation of the medial temporal lobe

The medial temporal lobe (MTL) is critical for declarative memory formation. Several theories of MTL function propose functional distinctions between the different structures of the MTL, namely the hippocampus and the surrounding cortical areas. Furthermore, computational models and electrophysiological studies in animals suggest distinctions between the subregions of the hippocampus itself. Standard fMRI resolution is not sufficiently fine to resolve activity on the scale of hippocampal subregions. Several approaches to scanning the MTL at high resolutions have been made, however there are limitations to these approaches, namely difficulty in conducting group-level analyses. We demonstrate here techniques for scanning the MTL at high resolution and analyzing the high-resolution fMRI data at the group level. To address the issue of cross-participant alignment, we employ the ROI-LDDMM alignment technique, which is demonstrated to result in smaller alignment errors when compared with several other common normalization techniques. Finally, we demonstrate that the pattern of activation obtained in the high-resolution functional data is similar to that obtained at lower resolution, although the spatial extent is smaller and the percent signal change is greater. This difference in the pattern of activation may be due to less partial volume sampling in the high-resolution data, resulting in more accentuated regions of activation.     

Distributed category‐specific recognition‐memory signals in human perirhinal cortex

Evidence from a large body of research suggests that perirhinal cortex (PrC), which interfaces the medial temporal lobe with the ventral visual pathway for object identification, plays a critical role in item‐based recognition memory. The precise manner in which PrC codes for the prior occurrence of objects, however, remains poorly understood. In the present functional magnetic resonance imaging (fMRI) study, we used multivoxel pattern analyses to examine whether the prior occurrence of faces is coded by distributed patterns of PrC activity that consist of voxels with decreases as well as increases in signal. We also investigated whether pertinent voxels are preferentially tuned to the specific object category to which judged stimuli belong. We found that, when no a priori constraints were imposed on the direction of signal change, activity patterns that allowed for successful classification of recognition‐memory decisions included some voxels with decreases and others with increases in signal in association with perceived prior occurrence. Moreover, successful classification was obtained in the absence of a mean difference in activity across the set of voxels in these patterns. Critically, we observed a positive relationship between classifier accuracy and behavioral performance across participants. Additional analyses revealed that voxels carrying diagnostic information for classification of memory decisions showed category specificity in their tuning for faces when probed with an independent functional localizer in a nonmnemonic task context. These voxels were spatially distributed in PrC, and extended beyond the contiguous voxel clusters previously described as the anterior temporal face patch. Our findings provide support for proposals, recently raised in the neurophysiological literature, that the prior occurrence of objects is coded by distributed PrC representations. They also suggest that the stimulus category to which an item belongs shapes the organization of these distributed representations. © 2015 Wiley Periodicals, Inc.     

Hippocampal lesions that abolish spatial maze performance spare object recognition memory at delays of up to 48 hours

The hippocampus is widely considered to be a critical component of a medial temporal lobe memory system, necessary for normal performance on tests of declarative memory. Object recognition memory is thought to be a classic test of declarative memory function. However, previous tests of the effects of hippocampal lesions on object recognition memory have not always supported this view. One possible reason for this inconsistency is that previously reported effects of hippocampal lesions on object recognition memory tasks may have stemmed not from a deficit in object recognition memory per se, but as a result of spatial and contextual confounds in the task. Thus, in the present study, we used a spontaneous object recognition test in a modified apparatus designed to minimize spatial and contextual factors. A group of rats with complete excitotoxic lesions of the hippocampus and a group of control rats were tested on this modified spontaneous object recognition task with retention delays of up to 48 h. These rats were also tested on a spatial nonmatching-to-place task. Spatial memory performance was abolished following hippocampal lesions, whereas performance on the recognition memory task was intact at all delays tested.     

Medial temporal lobe activation during context-dependent relational processes in episodic retrieval: an fMRI study. Functional magnetic resonance imaging

Previous studies have reported that the medial temporal lobe (MTL) structures contribute to the processing of relations among multiple stimuli in episodic encoding. There have been few studies, however, on the episodic retrieval requiring processing of relations among multiple components that was involved in our events. We used functional magnetic resonance imaging (fMRI) to investigate neural activities during the retrieval of relations within an organized episode and the recognition of an episodic component. Healthy, normal participants memorized 50 four-scene comic strips before fMRI scanning. In the retrieval phase with fMRI scanning, participants were engaged in three tasks: a visual identification (VI) task, a story recall (SR) task, and a picture recognition (PRe) task. In the VI task, participants were asked to judge whether they could identify at least one female character in the two scenes presented vertically. In the SR task, participants were shown the first and last scenes from strips memorized previously and asked to judge whether or not the two scenes were from the same strip. In the PRe task, participants were shown two scenes and asked to judge whether they both belonged to the memorized scenes. The two contrasts of SR with VI and PRe with VI demonstrated some commonly activated areas, such as the bilateral middle frontal gyrus and cerebellum. More importantly, the SR task differentially activated the bilateral parahippocampal gyrus, whereas the PRe task differentially activated right prefrontal areas, including the inferior frontal and precentral gyri. The results suggest that the activity of the MTL structures may be strongly associated with episodic memory retrieval requiring context-dependent relational processing.     

Encoding and retrieval along the long axis of the hippocampus and their relationships with dorsal attention and default mode networks: The HERNET model

The encoding of sensory input is intertwined with external attention, whereas retrieval is intrinsically related to internal attention. This study proposes a model in which the encoding of sensory input involves mainly the anterior hippocampus and the external attention network, whereas retrieval, the posterior hippocampus and the internal attention network. This model is referred to as the HERNET (hippocampal encoding/retrieval and network) model. Functional neuroimaging studies have identified two intrinsic large‐scale networks closely associated with external and internal attention, respectively. The dorsal attention network activates during any externally oriented mental activity, whereas the default mode network shows increased activity during internally oriented mental activity. Therefore, the HERNET model may predict the activation of the anterior hippocampus and the dorsal attention network during the encoding and activation of the posterior hippocampus and the default mode network during retrieval. To test this prediction, this study provides a meta‐analysis of three memory‐imaging paradigms: subsequent memory, laboratory‐based recollection, and autobiographical memory retrieval. The meta‐analysis included 167 individual studies and 2,856 participants. The results provide support for the HERNET model and suggest that the anterior–posterior gradient of encoding and retrieval includes amygdala regions. More broadly, humans continuously oscillate between external and internal attention and thus between encoding and retrieval processes. These oscillations may involve repetitive and spontaneous activity switching between the anterior hippocampus/dorsal attention network and the posterior hippocampus/default mode network. © 2014 Wiley Periodicals, Inc.     

Two separate,but interacting,neural systems for familiarity and novelty detection: A dual‐route mechanism

It has long been assumed that familiarity‐ and novelty‐related processes fall on a single continuum drawing on the same cognitive and neural mechanisms. The possibility that familiarity and novelty processing involve distinct neural networks was explored in a functional magnetic resonance imaging study (fMRI), in which familiarity and novelty judgments were made in contexts emphasizing either familiarity or novelty decisions. Parametrically modulated BOLD responses to familiarity and novelty strength were isolated in two separate, nonoverlapping brain networks. The novelty system involved brain regions along the ventral visual stream, the hippocampus, and the perirhinal and parahippocampal cortices. The familiarity system, on the other hand, involved the dorsomedial thalamic nucleus, and regions within the medial prefrontal cortex and the medial and lateral parietal cortex. Convergence of the two networks, treating familiarity and novelty as a single continuum was only found in a fronto‐parietal network. Finally, the orbitomedial prefrontal cortex was found to be sensitive to reported strength/confidence, irrespective of stimulus' familiarity or novelty. This pattern of results suggests a dual‐route mechanism supported by the existence of two distinct but interacting functional systems for familiarity and novelty. Overall, these findings challenge current assumptions regarding the neural systems that support the processing of novel and familiar information, and have important implications for research into the neural bases of recognition memory. © 2014 Wiley Periodicals, Inc.     

Differential responsivity of neurons in perirhinal cortex,lateral entorhinal cortex,and dentate gyrus during time‐bridging learning

Many studies have focused on the function of hippocampal region CA1 as a critical site for associative memory, but much less is known about changes in the afferents to CA1. Here we report the activity of multiple single neurons from perirhinal and entorhinal cortex and from dentate gyrus during trace eyeblink conditioning as well as consolidated recall, and in pseudo‐conditioned control rabbits. We also report an analysis of theta activity filtered from the local field potential (LFP). Our results show early associative changes in single‐neuron firing rate as well as theta oscillations in lateral entorhinal cortex (EC) and dentate gyrus (DG), and increases in the number of responsive neurons in perirhinal cortex. In both EC and DG, a subset of neurons from conditioned animals exhibited an elevated baseline firing rate and large responses to the conditioned stimulus and trace period. A similar population of cells has been seen in DG and in medial, but not lateral, EC during spatial tasks, suggesting that lateral EC contains cells responsive to a temporal associative task. In contrast to recent studies in our laboratory that found significant CA1 contributions to long‐term memory, the activity profiles of neurons within EC and DG were similar for conditioned and pseudoconditioned rabbits during post‐consolidation sessions. Collectively these results demonstrate that individual subregions of medial temporal lobe differentially support new and remotely acquired memories. Neuron firing profiles were similar on training trials when conditioned responses were and were not exhibited, demonstrating that these temporal lobe regions represent the CS–US association and do not control the behavioral response. The analysis of theta activity revealed that theta power was modulated by the conditioning stimuli in both the conditioned and pseudoconditioned groups and that although both groups exhibited a resetting of phase to the corneal airpuff, only the conditioned group exhibited a resetting of phase to the whisker conditioned stimulus.     

Evidence for semantic learning in profound amnesia: an investigation with patient H.M

Until recently, it seemed unlikely that any semantic knowledge could be acquired following extensive bilateral damage to the medial temporal lobes (MTL). Although recent studies have demonstrated some semantic learning in amnesic patients, questions remain regarding the limits of this capacity and the extent to which it relies on those patients' residual MTL function. The present study examined whether detailed, semantic memory could be acquired by a patient with no functioning hippocampus. We used cued recall and forced-choice recognition tasks to investigate whether the patient H.M. had acquired knowledge of people who became famous after the onset of his amnesia. Results revealed that, with first names provided as cues, he was able to recall the corresponding famous last name for 12 of 35 postoperatively famous personalities. This number nearly doubled when semantic cues were added, suggesting that his knowledge of the names was not limited to perceptual information, but was incorporated in a semantic network capable of supporting explicit recall. In forced-choice recognition, H.M. discriminated 87% of postmorbid famous names from foils. Critically, he was able to provide uniquely identifying semantic facts for one-third of these recognized names, describing John Glenn, for example, as "the first rocketeer" and Lee Harvey Oswald as a man who "assassinated the president." Although H.M.'s semantic learning was clearly impaired, the results provide robust, unambiguous evidence that some new semantic learning can be supported by structures beyond the hippocampus proper.     

Perceptual learning, awareness, and the hippocampus

Declarative memory depends on the hippocampus and related medial temporal lobe and diencephalic structures. Declarative memory has usually been found to be available to conscious recollection. A recent study (Chun and Phelps, Nat Neurosci 1999;2:844-847) found that damage to the medial temporal lobe (including the hippocampus) impaired performance on a perceptual learning task, yet the learning was accomplished in the absence of memory for the stimuli. This finding raised the possibility that some hippocampus-dependent tasks may be inaccessible to awareness and may be performed without evoking conscious memory processes. Using the same task, we show that when damage is confined largely to the hippocampal formation, perceptual learning is intact. Thus, the available data suggest that damage limited to the hippocampal formation does not impair nonconscious (nondeclarative) memory. Further, the data do not contradict the idea that hippocampus dependent memory is accessible to conscious recollection. Finally, perceptual learning was impaired in patients, with extensive damage to the medial temporal lobe and with additional variable damage to lateral temporal cortex.     

Fronto-temporal dysregulation in remitted bipolar patients: an fMRI delayed-non-match-to-sample (DNMS) study

Objectives:  Bipolar disorder is associated with working memory (WM) impairments that persist during periods of symptomatic remission. However, the neural underpinnings of these deficits are not well understood.
Methods:  Fifteen clinically remitted bipolar patients and 15 demographically matched healthy controls underwent functional magnetic resonance imaging while performing a novel delayed-non-match-to-sample (DNMS) task. This nonverbal DNMS task involves two conditions, one requiring the organization of existing memory traces ('familiarity'), and one involving the formation of new memory traces ('novelty'). These processes are thought to differentially engage the prefrontal cortex and medial temporal lobe, respectively.
Results:  Although behavioral performance did not differ between groups, bipolar patients and controls exhibited significantly different patterns of neural activity during task performance. Patients showed relative hyperactivation in the right prefrontal gyrus and relative hypoactivation in visual processing regions compared to healthy subjects across both task conditions. During the novelty condition, patients showed a pattern of hypoactivation relative to controls in medial temporal regions, with relative hyperactivation in the anterior cingulate.
Conclusions:  These findings suggest that disruption in fronto-temporal neural circuitry may underlie memory difficulties frequently observed in patients with bipolar disorder.     

Dopamine D1 receptor activity modulates object recognition memory consolidation in the perirhinal cortex but not in the hippocampus

It has been proposed that distributed neuronal networks in the medial temporal lobe process different characteristics of a recognition event; the hippocampus has been associated with contextual recollection while the perirhinal cortex has been linked with familiarity. Here we show that D1 dopamine receptor activity in these two structures participates differentially in object recognition memory consolidation. The D1 receptor antagonist SCH23390 was infused bilaterally 15 min before a 5 min sample phase in either rats' perirhinal cortex or dorsal hippocampus, and they were tested 90 min for short‐term memory or 24 h later for long‐term memory. SCH23390 impaired long‐term memory when infused in the perirhinal cortex but not when infused in the hippocampus. Conversely, when the D1 receptor agonist SKF38393 was infused 10 min before a 3 min sample phase in the perirhinal cortex, long‐term memory was enhanced, however, this was not observed when the D1 agonist was infused in the hippocampus. Short‐term memory was spared when SCH23390 or SKF38393 were infused in the perirhinal cortex or the dorsal hippocampus suggesting that acquisition was unaffected. These results suggest that dopaminergic transmission in these medial temporal lobe structures have a differential involvement in object recognition memory consolidation. © 2013 Wiley Periodicals, Inc.     

The hippocampus is involved in mental navigation for a recently learned, but not a highly familiar environment: a longitudinal fMRI study

Functional magnetic resonance imaging (MRI) was used to investigate the hypothesis that memory for a large-scale environment is initially dependent on the hippocampus but is later supported by extra-hippocampal structures (e.g., precuneus, posterior parahippocampal cortex, and lingual gyrus) once the environment is well-learned. Participants were scanned during mental navigation tasks initially when they were newly arrived to the city of Toronto, and later after having lived and navigated within the city for 1 yr. In the first session, activation was observed in the right hippocampus, left precuneus, and postcentral gyrus. The second session revealed activation in the caudate and lateral temporal cortex, but not in the right hippocampus; additional activation was instead observed in the posterior parahippocampal cortex, lingual gyrus, and precuneus. These findings suggest that the right hippocampus is required for the acquisition of new spatial information but is not needed to represent this information when the environment is highly familiar.     

Medial temporal lobe activity for recognition of recent and remote famous names: an event-related fMRI study

Previous neuroimaging studies examining recognition of famous faces have identified activation of an extensive bilateral neural network [Gorno Tempini, M. L., Price, C. J., Josephs, O., Vandenberghe, R., Cappa, S. F., Kapur, N. et al. (1998). The neural systems sustaining face and proper-name processing. Brain, 121, 2103-2118], including the medial temporal lobe (MTL) and specifically the hippocampal complex [Haist, F., Bowden, G. J., & Mao, H. (2001). Consolidation of human memory over decades revealed by functional magnetic resonance imaging. Nature Neuroscience, 4, 1139-1145; Leveroni, C. L., Seidenberg, M., Mayer, A. R., Mead, L. A., Binder, J. R., & Rao, S. M. (2000). Neural systems underlying the recognition of familiar and newly learned faces. Journal of Neuroscience, 20, 878-886]. One model of hippocampal functioning in autobiographical, episodic memory retrieval argues that the hippocampal complex remains active in retrieval tasks regardless of time or age of memory (multiple trace theory, MTT), whereas another proposal posits that the hippocampal complex plays a time-limited role in retrieval of autobiographical memories. The current event-related fMRI study focused on the medial temporal lobe and its response to recognition judgments of famous names from two distinct time epochs (1990s and 1950s) in 15 right-handed healthy older adults (mean age=70 years). A pilot study with an independent sample of young and older subjects ensured that the stimuli were representative of a recent and remote time period. Increased MR signal activity was observed on a bilateral basis for both the hippocampus and parahippocampal gyrus (PHG) during recognition of familiar names from both the recent and remote time periods when compared to non-famous names. However, the impulse response functions in the right hippocampus and right PHG demonstrated a differential response to stimuli from different time epochs, with the 1990s names showing the greatest MR signal intensity change, followed by the 1950s names, followed by foils. The finding that recognition of famous names produced significant bilateral MTL activation regardless of time epoch relative to foils provides support for the MTT model. However, the finding of a temporal gradient in the right MTL also provides support for the HC model, given the greater MTL response associated with recently famous names relative to remotely famous names.     

Evidence for a specific role of the anterior hippocampal region in successful associative encoding

It has been well established that the hippocampal formation plays a critical role in the formation of memories. However, functional specialization within the hippocampus remains controversial. Using functional magnetic resonance imaging (fMRI) during a face-name associative encoding task, followed by a postscan recognition test for face memory and face-name pair memory, we investigated the roles of anterior and posterior hippocampal regions in successful encoding of associations and items. Whole-brain and region of interest (ROI) analyses revealed that the anterior hippocampal formation showed increased activation for subsequently remembered face-name associations compared with pairs that were forgotten. In contrast, the posterior hippocampal formation showed activation above baseline during attempted encoding of face-name pairs, but no evidence of differential activation based on subsequent memory. Furthermore, exploratory whole-brain analyses revealed that a parahippocampal region, most likely corresponding to perirhinal cortex, showed subsequent memory effects for faces. These data provide evidence for functional specialization within the hippocampal formation based on the associative nature of the stimuli and subsequent memory.     

"I have often walked down this street before": fMRI studies on the hippocampus and other structures during mental navigation of an old environment

The role of the hippocampus in recent spatial memory has been well documented in patients with damage to this structure, but there is now evidence that the hippocampus may not be needed for the storage and recovery of a spatial layout that was experienced long before injury. Such preservation may rely, instead, on a network of dissociable, extra-hippocampal regions implicated in topographical orientation. Using functional magnetic resonance imaging (fMRI), we investigated this hypothesis in healthy individuals with extensive experience navigating in a large-scale urban environment (downtown Toronto). Participants were scanned as they performed mental navigation tasks that emphasized different types of spatial representations. Tasks included proximity judgments, distance judgments, landmark sequencing, and blocked-route problem-solving. The following regions were engaged to varying degrees depending on the processing demands of each task: retrosplenial cortex, believed to be involved in assigning directional significance to locales within a relatively allocentric framework; medial and posterior parietal cortex, concerned with processing space within egocentric coordinates during imagined movement; and regions of prefrontal cortex, present in tasks heavily dependent on working memory. In a second, event-related experiment, a distinct area of inferotemporal cortex was revealed during identification of familiar landmarks relative to unknown buildings in addition to activation of many of those regions identified in the navigation tasks. This result suggests that familiar landmarks are strongly integrated with the spatial context in which they were experienced. Importantly, right medial temporal lobe activity was observed, its magnitude equivalent across all tasks, though the core of the activated region was in the parahippocampal gyrus, barely touching the hippocampus proper.     

Interfering with Fos expression in rat perirhinal cortex impairs recognition memory

Previous work has shown that immunohistochemical imaging of Fos protein is a reliable marker for changes in activity related to recognition memory in the perirhinal (PRH) cortex of the medial temporal lobe; however, whether PRH Fos expression is necessary for recognition memory had not been established. To investigate this potential requirement, antisense Fos oligodeoxynucleotide (ODN) was infused locally into PRH cortex to interfere with Fos production. As in previous studies, differential Fos expression produced by viewing novel or familiar visual stimuli was measured by immunohistochemistry: antisense Fos ODN infusion into PRH cortex disrupted the normal pattern of differential Fos expression in PRH cortex. The effect of antisense Fos ODN infusion into PRH cortex was therefore sought on recognition memory. Infusion before or immediately after acquisition impaired recognition memory for objects when the memory delay was 3 or 24 h, but not when the delay was 20 min, or when the ODN was infused before retrieval after a 24‐h delay. The findings indicate a role for Fos in consolidation processes underlying long‐term recognition memory for objects and establish that interfering with its expression impairs recognition memory. Antisense Fos ODN infusion also impaired object‐in‐place recognition memory. The results demonstrate that Fos is necessary for neuronal mechanisms in PRH cortex essential to recognition memory. © 2012 Wiley Periodicals, Inc.