Non-spatial Recognition Memory Research Articles

Quercetin Inhibits Neuronal Pyroptosis and Ferroptosis by Modulating Microglial M1/M2 Polarization in Atherosclerosis.

Atherosclerosis (AS) with iron and lipid overload and systemic inflammation is a risk factor for Alzheimer's disease. M1 macrophage/microglia participate in neuronal pyroptosis and recently have been reported to be the ferroptosis-resistant phenotype. Quercetin plays a prominent role in preventing and treating neuroinflammation, but the protective mechanism against neurodegeneration caused by iron deposition is poorly understood. ApoE-/- mice were fed a high-fat diet with or without quercetin treatment. The Morris water maze and novel object recognition tests were conducted to assess spatial learning and memory, and nonspatial recognition memory, respectively. Prussian blue and immunofluorescence staining were performed to assess the iron levels in the whole brain and in microglia, microglia polarization, and the degree of microglia/neuron ferroptosis. In vitro, we further explored the molecular biological alterations associated with microglial polarization, neuronal pyroptosis, and ferroptosis via Western blot, flow cytometry, CCK8, LDH, propidium iodide, and coculture system. We found that quercetin improved brain lesions and spatial learning and memory in AS mice. Iron deposition in the whole brain or microglia was reversed by the quercetin treatment. In the AS group, the colocalization of iNOS with Iba1 was increased, which was reversed by quercetin. However, the colocalization of iNOS with PTGS2/TfR was not increased in the AS group, suggesting a character resisting ferroptosis. Quercetin induced the expression of Arg-1 and decreased the colocalizations of Arg-1 with PTGS2/TfR. In vitro, ox-LDL combined with ferric ammonium citrate treatment (OF) significantly shifted the microglial M1/M2 phenotype balance and increased the levels of free iron, ROS, and lipid peroxides, which was reversed by quercetin. M1 phenotype induced by OF caused neuronal pyroptosis and was promoted to ferroptosis by L-NIL treatment, which contributed to neuronal ferroptosis as well. However, quercetin induced the M1 to M2 phenotype and inhibited M2 macrophages/microglia and neuron pyroptosis or ferroptosis. In summary, quercetin alleviated neuroinflammation by inducing the M1 to M2 phenotype to inhibit neuronal pyroptosis and protected neurons from ferroptosis, which may provide a new idea for neuroinflammation prevention and treatment.

The Nitric Oxide (NO) Donor Molsidomine Attenuates Memory Impairments Induced by the D1/D2 Dopaminergic Receptor Agonist Apomorphine in the Rat.

Several lines of evidence suggest that scarcity of the gaseous molecule nitric oxide (NO) is associated with the pathogenesis of schizophrenia. Therefore, compounds, such as NO donors, that can normalize NO levels might be of utility for the treatment of this pathology. It has been previously shown that the NO donor molsidomine attenuated schizophrenia-like behavioral deficits caused by glutamate hypofunction in rats. The aim of the current study was to investigate the efficacy of molsidomine and that of the joint administration of this NO donor with sub-effective doses of the non-typical antipsychotics clozapine and risperidone to counteract memory deficits associated with dysregulation of the brain dopaminergic system in rats. Molsidomine (2 and 4 mg/kg) attenuated spatial recognition and emotional memory deficits induced by the mixed dopamine (DA) D1/D2 receptor agonist apomorphine (0.5 mg/kg). Further, the joint administration of sub-effective doses of molsidomine (1 mg/kg) with those of clozapine (0.1 mg/kg) or risperidone (0.03 mg/kg) counteracted non-spatial recognition memory impairments caused by apomorphine. The present findings propose that molsidomine is sensitive to DA dysregulation since it attenuates memory deficits induced by apomorphine. Further, the current findings reinforce the potential of molsidomine as a complementary molecule for the treatment of schizophrenia.

The Nitric Oxide (NO) Donor Molsidomine Counteract Social Withdrawal and Cognition Deficits Induced by Blockade of the NMDA Receptor in the Rat

The deficiency of the gaseous molecule nitric oxide (NO) seems to be critically involved in the pathogenesis of schizophrenia. Thus, molecules that can normalize NO levels, as are NO donors, might be of utility for the medication of this psychiatric disease. The aim of the present study was to detect the ability of the NO donor molsidomine to reduce schizophrenia-like impairments produced by the blockade of the N-methyl-D-aspartate (NMDA) receptor in rats. Molsidomine's ability to attenuate social withdrawal and spatial recognition memory deficits induced by the NMDA receptor antagonist ketamine were assessed using the social interaction and the object location test, respectively. Further, the efficacy of the combination of sub-effective doses of molsidomine with sub-effective doses of the atypical antipsychotic clozapine in alleviating non-spatial recognition memory deficits was evaluated utilizing the object recognition task. Molsidomine (2 and 4 mg/kg) attenuated social withdrawal and spatial recognition memory deficits induced by ketamine. Co-administration of inactive doses of molsidomine (1 mg/kg) and clozapine (0.1 mg/kg) counteracted delay-dependent and ketamine-induced non-spatial recognition memory deficits. The current findings suggest that molsidomine is sensitive to glutamate hypofunction since it attenuated behavioral impairments in animal models mimicking the negative symptoms and cognitive deficits of schizophrenia. Additionally, the present results support the potential of molsidomine as an adjunctive drug for the therapy of schizophrenia.

Dietary Methionine via Dose-Dependent Inhibition of Short-Chain Fatty Acid Production Capacity Contributed to a Potential Risk of Cognitive Dysfunction in Mice.

High-methionine diets induce impaired learning and memory function, dementia-like neurodegeneration, and Alzheimer's disease, while low-methionine diets improve learning and memory function. We speculated that variations in intestinal microbiota may mediate these diametrically opposed effects; thus, this study aimed to verify this hypothesis. The ICR mice were fed either a low-methionine diet (LM, 0.17% methionine), normal methionine diet (NM, 0.86% methionine), or high-methionine diet (HM, 2.58% methionine) for 11 weeks. We found that HM diets damaged nonspatial recognition memory, working memory, and hippocampus-dependent spatial memory and induced anxiety-like behaviors in mice. LM diets improved nonspatial recognition memory and hippocampus-dependent spatial memory and ameliorated anxiety-like behavior, but the differences did not reach a significant level. Moreover, HM diets significantly decreased the abundance of putative short-chain fatty acid (SCFA)-producing bacteria (Roseburia, Blautia, Faecalibaculum, and Bifidobacterium) and serotonin-producing bacteria (Turicibacter) and significantly increased the abundance of proinflammatory bacteria Escherichia-Shigella. Of note, LM diets reversed the results. Consequently, the SCFA and serotonin levels were significantly decreased with HM diets and significantly increased with LM diets. Furthermore, HM diets induced hippocampal oxidative stress and inflammation and selectively downregulated the hippocampus-dependent memory-related gene expression, whereas LM diets selectively upregulated the hippocampus-dependent memory-related gene expression. In conclusion, dietary methionine via dose-dependent inhibition of SCFA production capacity contributed to a potential risk of cognitive dysfunction in mice.

Crocins, the Bioactive Components of Crocus sativus L., Counteract the Disrupting Effects of Anesthetic Ketamine on Memory in Rats.

Consistent experimental evidence suggests that anesthetic doses of the non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist ketamine cause severe memory impairments in rodents. Crocins are among the various bioactive ingredients of the plant Crocus sativus L., and their implication in memory is well-documented. It has not yet been elucidated if crocins are able to attenuate the memory deficits produced by anesthetic ketamine. The present study was undertaken aiming to clarify this issue in the rat. For this aim, the object recognition, the object location and the habituation tests, reflecting non-spatial recognition memory, spatial recognition memory and associative memory, respectively, were utilized. A post-training challenge with crocins (15–30 mg/kg, intraperitoneally (i.p.), acutely) counteracted anesthetic ketamine (100 mg/kg, i.p.)-induced performance impairments in all the above-mentioned behavioral memory paradigms. The current findings suggest that crocins modulate anesthetic ketamine’s amnestic effects.

Spatial Coding in the Subiculum Requires Anterior Thalamic Inputs

Hippocampal function relies on the anterior thalamic nuclei, yet the reasons remain poorly understood. While anterior thalamic lesions disrupt parahippocampal spatial signalling, their impact on the subiculum is unknown, despite the importance of this area for hippocampal networks. We recorded subiculum cells in rats with either permanent (N-methyl-D-aspartic acid) or reversible (muscimol) anterior thalamic lesions. The diverse spatial signals normally found in the subiculum, including place cells, disappeared following permanent thalamic lesions and showed marked disruption during transient lesions. Meanwhile, permanent anterior thalamic lesions had no discernible impact on CA1 place fields. Thalamic lesions reduced spatial alternation performance (permanently or reversibly) to chance levels, while leaving a non-spatial recognition memory task unaffected. These findings, which help to explain why anterior thalamic damage is so deleterious for spatial memory, cast a new spotlight on the importance of subiculum function, and reveal its dependence on anterior thalamic signalling.

Enhancement of cognitive functions by rice bran extract in a neuroinflammatory mouse model via regulation of PPARγ

Activation of the peroxisome proliferator-activated receptor gamma (PPARγ), has been recently demonstrated to attenuate inflammatory response and improve cognitive dysfunction in neurodegenerative diseases. RBE is rich in polyunsaturated fatty acids, which were recently considered as new PPARγ modulators. Accordingly, the effect of RBE on memory and cognition in a neuroinflammatory mouse model was examined to investigate whether RBE improves cognition through modulating PPARγ. RBE administration significantly improved the spatial working, reference memory and non-spatial recognition memory where the effect was abolished in the presence of a PPARγ antagonist (GW9662). Moreover, nuclear brain extracts obtained from mice treated with RBE showed increase in the PPARγ binding to its response element, indicating activation of the receptor, which was attenuated in the presence of GW9662. These findings demonstrate that the involvement of RBE in the beneficial effects on cognitive performance is correlated with its action on PPARγ receptors.

Beneficial effects of environmental enrichment on behavior, stress reactivity and synaptophysin/BDNF expression in hippocampus following early life stress

Exposure to environmental enrichment can beneficially influence the behavior and enhance synaptic plasticity. The aim of the present study was to investigate the mediated effects of environmental enrichment on postnatal stress-associated impact with regard to behavior, stress reactivity as well as synaptic plasticity changes in the dorsal hippocampus. Wistar rat pups were submitted to a 3 h maternal separation (MS) protocol during postnatal days 1–21, while another group was left undisturbed. On postnatal day 23, a subgroup from each rearing condition (maternal separation, no-maternal separation) was housed in enriched environmental conditions until postnatal day 65 (6 weeks duration). At approximately three months of age, adult rats underwent behavioral testing to evaluate anxiety (Elevated Plus Maze), locomotion (Open Field Test), spatial learning and memory (Morris Water Maze) as well as non-spatial recognition memory (Novel Object Recognition Test). After completion of behavioral testing, blood samples were taken for evaluation of stress-induced plasma corticosterone using an enzyme-linked immunosorbent assay (ELISA), while immunofluorescence was applied to evaluate hippocampal BDNF and synaptophysin expression in dorsal hippocampus. We found that environmental enrichment protected against the effects of maternal separation as indicated by the lower anxiety levels and the reversal of spatial memory deficits compared to animals housed in standard conditions. These changes were associated with increased BDNF and synaptophysin expression in the hippocampus. Regarding the neuroendocrine response to stress, while exposure to an acute stressor potentiated corticosterone increases in maternally-separated rats, environmental enrichment of these rats prevented this effect. The current study aimed at investigating the compensatory role of enriched environment against the negative outcomes of adverse experiences early in life concurrently on emotional and cognitive behaviors, HPA function and neuroplasticity markers.

Carbonic anhydrase activation enhances object recognition memory in mice through phosphorylation of the extracellular signal-regulated kinase in the cortex and the hippocampus

Rats injected with by d-phenylalanine, a carbonic anhydrase (CA) activator, enhanced spatial learning, whereas rats given acetazolamide, a CA inhibitor, exhibited impairments of fear memory consolidation. However, the related mechanisms are unclear. We investigated if CAs are involved in a non-spatial recognition memory task assessed using the object recognition test (ORT). Systemic administration of acetazolamide to male CD1 mice caused amnesia in the ORT and reduced CA activity in brain homogenates, while treatment with d-phenylalanine enhanced memory and increased CA activity. We provided also the first evidence that d-phenylalanine administration rapidly activated extracellular signal-regulated kinase (ERK) pathways, a critical step for memory formation, in the cortex and the hippocampus, two brain areas involved in memory processing. Effects elicited by d-phenylalanine were completely blunted by co-administration of acetazolamide, but not of 1-N-(4-sulfamoylphenyl-ethyl)-2,4,6-trimethylpyridinium perchlorate (C18), a CA inhibitor that, differently from acetazolamide, does not cross the blood brain barrier. Our results strongly suggest that brain but not peripheral CAs activation potentiates memory as a result of ERK pathway enhanced activation.

The novel dehydroepiandrosterone (DHEA) derivative BNN27 counteracts delay-dependent and scopolamine-induced recognition memory deficits in rats

Experimental evidence indicates that the neurosteroids dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) are involved in cognition. BNN27 is a novel 17C spiroepoxy-DHEA derivative, which devoid of steroidogenic activity. The neuroprotective effects of BNN27 have been recently reported. The present study was designed to investigate the effects of BNN27 on recognition memory in rats. For this purpose, the novel object task (NOT), a procedure assessing non-spatial recognition memory and the novel location task (NLT), a procedure evaluating spatial recognition memory were used. Intraperitoneal (i.p.) administration of BNN27 (3 and 10mg/kg) antagonized delay-dependent deficits in the NOT in the normal rat, suggesting that this DHEA derivative affected acquisition, storage and retrieval of information. In addition, BNN27 (3 and 10mg/kg, i.p.) counteracted the scopolamine [0.2mg/kg, subcutaneously (s.c.)]-induced non-spatial and spatial recognition memory deficits. These findings suggest that BNN27 may modulate different aspects of recognition memory, potentially interacting with the cholinergic system, relevant to cognition.

Crocins, the active constituents of Crocus sativus L., counteracted apomorphine-induced performance deficits in the novel object recognition task, but not novel object location task, in rats

Schizophrenia is a chronic mental disease that affects nearly 1% of the population worldwide. Several lines of evidence suggest that the dopaminergic (DAergic) system might be compromised in schizophrenia. Specifically, the mixed dopamine (DA) D1/D2 receptor agonist apomorphine induces schizophrenia-like symptoms in rodents, including disruption of memory abilities. Crocins are among the active components of saffron (dried stigmas of Crocus sativus L. plant) and their implication in cognition is well documented. The present study investigated whether crocins counteract non-spatial and spatial recognition memory deficits induced by apomorphine in rats. For this purpose, the novel object recognition task (NORT) and the novel object location task (NOLT) were used. The effects of compounds on mobility in a locomotor activity chamber were also investigated in rats. Post-training peripheral administration of crocins (15 and 30mg/kg) counteracted apomorphine (1mg/kg)-induced performance deficits in the NORT. Conversely, crocins did not attenuate spatial recognition memory deficits produced by apomorphine in the NOLT. The present data show that crocins reversed non-spatial recognition memory impairments produced by dysfunction of the DAergic system and modulate different aspects of memory components (storage and/or retrieval). The effects of compounds on recognition memory cannot be attributed to changes in locomotor activity. Further, our findings illustrate a functional interaction between crocins and the DAergic system that may be of relevance for schizophrenia-like behavioral deficits. Therefore, the utilization of crocins as an adjunctive agent, for the treatment of cognitive deficits observed in schizophrenic patients should be further investigated.

The Effect of Curcumin on Anxiety and Recognition Memory in Kainate Model of Epileptic Rats

The effect of curcumin had been studied on anxiety and recognition memory in kainic acid-induced epilepsy. A single dose of intraperitoneal kainic acid (10 mg/kg) was used to induce status epilepticus in female Wistar rats, followed by respective treatments (vehicle dimethyl sulfoxide 50%, curcumin 100 mg/kg/d or levetiracetam 100 mg/kg/d) on the next day for 7 d, with minimum of six rats per group. The behavioural tests were performed before seizure induction and after treatment. Vehicle-treated epileptic rats showed an increase in anxiety-like behaviours in the open field test, which less observed in the light/dark box test. Levetiracetam-treated epileptic rats exhibited anxiolytic behaviours in both the tests. Curcumin-treated epileptic rats exhibited not much difference in anxiety-like behaviour before and after the treatment in open field test, but exhibited anxiolytic behaviours in light/dark box test. Kainic acid impaired the both spatial and non-spatial recognition memories of the rats. Curcumin treatment showed reversal in the non-spatial recognition impaired by kainic acid. In conclusion, kainic acid increases anxiety-like behaviours and impaired recognition memories during the early phase of epileptogenesis and curcumin was potentially improved anxiety and non-spatial recognition memory impaired by kainic acid. These benefits highlighted the potential effect of curcumin to improve psychiatric disorders in epilepsy.

Evidences of the role of the rodent hippocampus in the non-spatial recognition memory

The hippocampus is a key region responsible for processing spatial information. However, the role of the hippocampus in non-spatial recognition memory is still controversial. In the present study, we performed hippocampal lesioning to address this controversy. The hippocampi of mice were disrupted with bilateral cytotoxic lesions, and standard object recognition (non-spatial) and object location recognition (spatial) were tested. In the habituation period, mice with hippocampal lesions needed a significantly longer time to fully habituate to the test box. Interestingly, after 4 days of habituation (insufficient habituation), the recognition index was similar in the sham and hippocampal lesion groups. However, exploration time was significantly shorter in mice with hippocampal lesions compared with that in control mice. Interestingly, if mice were subjected to a 10-days-long period of habituation (full habituation), the recognition index was significantly lower in mice with hippocampal lesions compared with that in control mice; however, total exploration time was similar in both groups. Furthermore, the object recognition test after full habituation occluded hippocampal long-term potentiation, a cellular model of memory. These results indicate that sufficient habituation is required to observe the effects of hippocampal lesions on object recognition memory.

Cerebrolysin improves cognitive performance in rats after mild traumatic brain injury

Long-term memory deficits occur after mild traumatic brain injuries (mTBIs), and effective treatment modalities are currently unavailable. Cerebrolysin, a peptide preparation mimicking the action of neurotrophic factors, has beneficial effects on neurodegenerative diseases and brain injuries. The present study investigated the long-term effects of Cerebrolysin treatment on cognitive function in rats after mTBI. Rats subjected to closed-head mTBI were treated with saline (n = 11) or Cerebrolysin (2.5 ml/kg, n = 11) starting 24 hours after injury and then daily for 28 days. Sham animals underwent surgery without injury (n = 8). To evaluate cognitive function, the modified Morris water maze (MWM) test and a social odor-based novelty recognition task were performed after mTBI. All rats were killed on Day 90 after mTBI, and brain sections were immunostained for histological analyses of amyloid precursor protein (APP), astrogliosis, neuroblasts, and neurogenesis. Mild TBI caused long-lasting cognitive memory deficits in the MWM and social odor recognition tests up to 90 days after injury. Compared with saline treatment, Cerebrolysin treatment significantly improved both long-term spatial learning and memory in the MWM test and nonspatial recognition memory in the social odor recognition task up to 90 days after mTBI (p < 0.05). Cerebrolysin significantly increased the number of neuroblasts and promoted neurogenesis in the dentate gyrus, and it reduced APP levels and astrogliosis in the corpus callosum, cortex, dentate gyrus, CA1, and CA3 regions (p < 0.05). These results indicate that Cerebrolysin treatment of mTBI improves long-term cognitive function, and this improvement may be partially related to decreased brain APP accumulation and astrogliosis as well as increased neuroblasts and neurogenesis.

Processing of spatial and non-spatial information reveals functional homogeneity along the dorso-ventral axis of CA3, but not CA1

The ventral hippocampus is thought to principally contribute to emotional memory, while its dorsal part would be more involved in spatial processes. However, few studies have investigated ventral hippocampal function in spatial or non-spatial memories devoid of strong emotional components, and conflicting results have emerged regarding the role of the dorsal hippocampus in non-spatial (object) recognition memory. Moreover, even fewer reports have dissociated the contribution of the hippocampal subfields CA1 and CA3 to those processes, despite growing evidence of a functional segregation between these subfields. In a recent study, we detected the immediate-early gene Arc, used as a marker of neuronal activity, during spontaneous spatial and non-spatial recognition memory tasks, and showed that dorsal CA3 was spatially tuned while dorsal CA1 processed spatial and non-spatial information to the same extent (Beer, Chwiesko, Kitsukawa, & Sauvage, 2013). Here, we analyze the pattern of Arc expression detected in ventral CA1 and CA3 to determine their role in spatial or non-spatial recognition memory, and investigate whether ventral CA1 and CA3 activation differs from that of their dorsal counterparts. We report that ventral CA1 and CA3 are recruited for both spatial and non-spatial memories, but more strongly for spatial memory (e.g. were spatially tuned), and that CA3 is functionally homogeneous along the dorso-ventral axis, but not CA1.

Proximodistal Segregation of Nonspatial Information in CA3: Preferential Recruitment of a Proximal CA3-Distal CA1 Network in Nonspatial Recognition Memory

A prevailing view in memory research is that CA3 principally supports spatial processes. However, few studies have investigated the contribution of CA3 to nonspatial memory function. Interestingly, the proximal part of CA3 (close to the dentate gyrus) predominantly projects to distal CA1 (away from the dentate gyrus), which preferentially processes nonspatial information. Moreover, the cytoarchitecture and connectivity patterns in the proximal and distal parts of CA3 strongly differ, suggesting a functional segregation in this area. Here, we tested whether CA3 is recruited during nonspatial recognition memory, and whether nonspatial information is differentially represented along the proximodistal axis of CA3. Furthermore, we investigated whether the pattern of activation within CA3 would mirror that of CA1. We used a high-resolution imaging technique specifically designed to analyze brain activity in distant areas that is based on the detection of the expression of the immediate-early gene Arc, used as a marker of neuronal activation. We showed that proximal CA3 is strongly recruited during a nonspatial delayed nonmatching-to-sample recognition memory task in rats, while distal CA3 is not. In addition, distal CA1 was more activated than proximal CA1 in the same task. These findings suggest a functional segregation of CA3 that mirrors that of CA1, and potentially indicate the existence of a proximal CA3-distal CA1 hippocampal subnetwork that would preferentially process nonspatial information during recognition memory.

Repeated mild hypoxic exposures decrease anxiety-like behavior in the adult mouse together with an increased brain adrenomedullin gene expression

Whereas severe hypoxia is known to contribute to neuronal death and to lead to neurological disturbances, mild hypoxia can also induce beneficial effects through endogenous adaptive responses. The aim of this study was to investigate the effects of mild hypoxia (8% O2) on cognitive and emotional behavior in the adult mouse. To this end, mice were submitted to repeated mild hypoxia exposure or normoxia during 6 weeks and underwent behavioral testing during the last 3 weeks. Hypoxia decreased anxiety-like behavior in the light/dark transition test, enhanced, albeit modestly, non-spatial recognition memory, but did not alter spontaneous locomotor activity, nor spatial learning. On additional mice, whole brain adrenomedullin mRNA expression was found to be increased at D1, D25 and D41 after hypoxia initiation and vascular endothelial growth factor (VEGF) mRNA expression was increased at only on D41. This work shows that repeated mild hypoxic exposure decreases anxiety-related behavior and points out hypoxia inducible factor-1 (HIF-1) target genes, particularly adrenomedullin, as potential mediator candidate.

Deletion of the GluA1 AMPA receptor subunit impairs recency-dependent object recognition memory

Deletion of the GluA1 AMPA receptor subunit impairs short-term spatial recognition memory. It has been suggested that short-term recognition depends upon memory caused by the recent presentation of a stimulus that is independent of contextual–retrieval processes. The aim of the present set of experiments was to test whether the role of GluA1 extends to nonspatial recognition memory. Wild-type and GluA1 knockout mice were tested on the standard object recognition task and a context-independent recognition task that required recency-dependent memory. In a first set of experiments it was found that GluA1 deletion failed to impair performance on either of the object recognition or recency-dependent tasks. However, GluA1 knockout mice displayed increased levels of exploration of the objects in both the sample and test phases compared to controls. In contrast, when the time that GluA1 knockout mice spent exploring the objects was yoked to control mice during the sample phase, it was found that GluA1 deletion now impaired performance on both the object recognition and the recency-dependent tasks. GluA1 deletion failed to impair performance on a context-dependent recognition task regardless of whether object exposure in knockout mice was yoked to controls or not. These results demonstrate that GluA1 is necessary for nonspatial as well as spatial recognition memory and plays an important role in recency-dependent memory processes.

The Caudal Medial Entorhinal Cortex: a Selective Role in Recollection-Based Recognition Memory

Recent studies have suggested that the caudal medial entorhinal cortex (cMEC) is specialized for path integration and spatial navigation. However, cMEC is part of a brain system that supports episodic memory for both spatial and nonspatial events, and so may play a role in memory function that goes beyond navigation. Here, we used receiver operating characteristic analysis to investigate the role of the cMEC in familiarity and recollection processes that underlie nonspatial recognition memory in rats. The results indicate that cMEC plays a critical and selective role in recollection-based performance, supporting the view that cMEC supports memory for the spatial and temporal context in which events occur.

Environmental Enrichment Influences BDNF and NR1 Levels in the Hippocampus and Restores Cognitive Impairment in Chronic Cerebral Hypoperfused Rats

An enriched environment (EE) is beneficial in modifying behaviors, particularly in tasks involving complex cognitive functions. However, the impact of EE on cognitive impairment induced by chronic cerebral hypoperfusion (CCH) has not been studied. We investigated the effects of EE on cognitive impairment caused by CCH and examined whether CCH altered the protein levels of brain-derived neurotrophic factor (BDNF) and N-methyl-D-aspartate (NMDA) receptor subunit 1 (NR1) and subunit 2B (NR2B) in the hippocampus of rats and whether EE exposure attenuated the effects. Rats were divided into four groups that received either permanent bilateral ligation of the common carotid arteries (2-vessel occlusion) surgery or sham surgery followed by either EE housing or standard environment housing for 4 weeks. We examined non-spatial recognition memory in the novel object recognition task, spatial learning, and memory ability in the Morris water maze as well as the protein levels of BDNF, NR1, and NR2B in the hippocampus. CCH impaired both spatial and non-spatial cognitive functions, and EE exposure reversed the spatial cognitive performance and improved non-spatial memory performance. CCH resulted in decreased levels of BDNF and NR1 protein in the hippocampus, and EE exposure restored the decreased expression. Our results demonstrate for the first time that EE exposure restores cognitive impairment induced by CCH and up-regulates the decreased protein levels of BDNF and NR1. Inversely, BDNF and NR1 may contribute to the beneficial effects of EE on CCH in rats.