Object Recognition Memory Task Research Articles

Chemogenetic activation or inhibition of histaminergic neurons bidirectionally modulates recognition memory formation and retrieval in male and female mice.

Several lines of evidence demonstrate that the brain histaminergic system is fundamental for cognitive processes and the expression of memories. Here, we investigated the effect of acute silencing or activation of histaminergic neurons in the hypothalamic tuberomamillary nucleus (TMNHA neurons) in vivo in both sexes in an attempt to provide direct and causal evidence of the necessary role of these neurons in recognition memory formation and retrieval. To this end, we compared the performance of mice in two non-aversive and non-rewarded memory tests, the social and object recognition memory tasks, which are known to recruit different brain circuitries. To directly establish the impact of inactivation or activation of TMNHA neurons, we examined the effect of specific chemogenetic manipulations during the formation (acquisition/consolidation) or retrieval of recognition memories. We consistently found that acute chemogenetic silencing of TMNHA neurons disrupts the formation or retrieval of both social and object recognition memory in males and females. Conversely, acute chemogenetic activation of TMNHA neurons during training or retrieval extended social memory in both sexes and object memory in a sex-specific fashion. These results suggest that the formation or retrieval of recognition memory requires the tonic activity of histaminergic neurons and strengthen the concept that boosting the brain histaminergic system can promote the retrieval of apparently lost memories.

Esketamine enhances memory reconsolidation in the novel object recognition task

Esketamine, the right-handed optical isomer of racemic ketamine, is a rapidly acting antidepressant approved by the FDA for treatment-resistant depression in 2019. However, few studies have investigated esketamine's role in learning and memory, particularly in the context of memory reconsolidation. Herein, we evaluated esketamine's role in memory reconsolidation in 7-week-old male Institute of Cancer Research mice subjected to the novel object recognition (NOR) memory task. The NOR reconsolidation procedure comprised three phases: sampling, reactivation, and testing. Esketamine-enhanced NOR memory performance when injected into mice 0 h after reactivation rather than following a 6 h delay. Conversely, administering esketamine 24 h after sampling without reactivation did not enhance NOR memory performance. Notably, esketamine exhibited no discernible effects on nonspecific responses, such as locomotor activity and exploratory behavior. Furthermore, the α-amino-3‑hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type receptor antagonist NBQX effectively blocked the esketamine-induced enhancement of memory reconsolidation. In conclusion, esketamine treatment markedly improves memory reconsolidation in NOR tasks, and this effect is linked to AMPA receptor activity.

Electrophysiological evidence for context reinstatement effects on object recognition memory

Reinstating the context present at encoding during the test phase generally enhances recognition memory compared with changing the context when specific item–context associations are established during encoding. However, it remains unclear whether context reinstatement improves the performance in differentiating between old and similar items in recognition memory tests and what underlying cognitive processes are involved. Using the context reinstatement paradigm together with event-related potentials (ERP), we examined the context-dependent effects of background scenes on recognition discrimination among similar objects. Participants were instructed to associate intentionally specific objects with background scenes during the encoding phase and subsequently complete an object recognition memory task, during which old and similar new objects were presented superimposed over the studied old or similar new background scenes. Electroencephalogram was recorded to measure the electrophysiological manifestations of cognitive processes associated with episodic retrieval. Behavioral results revealed enhanced performance in differentiating old from similar objects in the old context, as opposed to the similar context condition. Importantly, ERP results indicated a more pronounced recollection-related parietal object old/new effect in the old context compared to the similar context condition. This suggests that the ability to distinguish between old and similar objects in recognition memory is primarily driven by recollection rather than familiarity, particularly when the encoding context is reinstated during the test phase. Our findings are in line with the account that the impact of context reinstatement on object recognition memory is attributable to the enhanced recollection of specific item–context associations during retrieval and provides evidence for the specificity of episodic associative representations.

Capparis sepiaria’s root bark aqueous lyophilisate shows antiamnesic properties on scopolamine induce cognitive impairment in mice

Capparis sepiaria (Capparaceae) is a plant used in African traditional medicine to treat psychiatic disorders. The aim of this study was to assess the anti-amnesic effect of aqueous lyophilisate of the root bark of Capparis sepiaria (C. sepiaria) on scopolamine-induced animal model of memory impairment using Swiss albino adult mice of both sexes. Memory integrity was assessed by Morris water Maze test, Novel Object Recognition (NOR) and Object-location memory (OLT) tasks were used to assess behavioural components of memory processes and learning. Malondialdehyde (MDA), reduced glutathione (GSH), NO levels and catalase were used to assess oxidative stress while acethylcholinesterase activity was used to evaluate acetylcholine activity in the hippocampus tissues. The quantitative phytochemistry and acute toxicity of the roots of C. sepiaria were also evaluated. The aqueous lyophilisate of C. sepiaria at doses of 10 mg/kg and 40 mg/kg significantly increased the discrimination index in the Morris Water Maze and the objet location tasks. The aqueous lyophilisate of C. sepiaria significantly increased hippocampal GSH and catalase levels and decreased hippocampal MDA, NO levels and achetylcholinesterase (AChE) activities. The aqueous lyophilisate of C. sepiaria showed no acute toxicity with a LD50 > 5000 mg/kg, and revealed a content of flavonoids, tannins and phenols. These results suggest that C. sepiaria improve memory impairment induced by scopolamine and therefore possess antiamnesic properties. These properties would result from a modulation of cholinergic neurotransmission as well as an antioxidant activity of the plant.

Effect of neonatal melatonin administration on behavioral and brain electrophysiological and redox imbalance in rats.

Melatonin (MLT) reportedly has beneficial effects in neurological disorders involving brain excitability (e.g., Epilepsy and Migraine) and behavioral patterns (e.g., Anxiety and Depression). This study was performed to investigate, in the developing rat brain, the effect of early-in-life administration of two different doses of exogenous MLT on behavioral (anxiety and memory) and electrophysiological (CSD analysis) aspects of brain function. Additionally, brain levels of malondialdehyde (MDA) and superoxide dismutase (SOD), both cellular indicators of redox balance status, were evaluated. We hypothesize that MLT differentially affects the behavioral and CSD parameters as a function of the MLT dose. Male Wistar rats received, from the 7th to the 27th postnatal day (PND), on alternate days, vehicle solution, or 10 mg/kg/or 40 mg/kg MLT (MLT-10 and MLT-40 groups), or no treatment (intact group). To perform behavioral and cognition analysis, from PND30 to PND32, they were tested in the open field apparatus, first for anxiety (PND30) and then for object recognition memory tasks: spatial position recognition (PND31) and shape recognition (PND32). On PND34, they were tested in the elevated plus maze. From PND36 to 42, the excitability-related phenomenon known as cortical spreading depression (CSD) was recorded, and its features were analyzed. Treatment with MLT did not change the animals' body weight or blood glucose levels. The MLT-10 treatment, but not the MLT-40 treatment, was associated with behaviors that suggest less anxiety and improved memory. MLT-10 and MLT-40 treatments, respectively, decelerated and accelerated CSD propagation (speed of 2.86 ± 0.14 mm/min and 3.96 ± 0.16 mm/min), compared with the control groups (3.3 ± 0.10 mm/min and 3.25 ± 0.11 mm/min, for the intact and vehicle groups, respectively; p < 0.01). Cerebral cortex levels of malondialdehyde and superoxide dismutase were, respectively, lower and higher in the MLT-10 group but not in the MLT40 group. Our findings suggest that MLT intraperitoneal administration during brain development may differentially act as an antioxidant agent when administered at a low dose but not at a high dose, according to behavioral, electrophysiological, and biochemical parameters.

Chronic exposure to inorganic arsenic and fluoride induces redox imbalance, inhibits the transsulfuration pathway, and alters glutamate receptor expression in the brain, resulting in memory impairment in adult male mouse offspring

Exposure to toxic elements in drinking water, such as arsenic (As) and fluoride (F), starts at gestation and has been associated with memory and learning deficits in children. Studies in which rodents underwent mechanistic single exposure to As or F showed that the neurotoxic effects are associated with their capacity to disrupt redox balance, mainly by diminishing glutathione (GSH) levels, altering glutamate disposal, and altering glutamate receptor expression, which disrupts synaptic transmission. Elevated levels of As and F are common in groundwater worldwide. To explore the neurotoxicity of chronic exposure to As and F in drinking water, pregnant CD-1 mice were exposed to 2 mg/L As (sodium arsenite) and 25 mg/L F (sodium fluoride) alone or in combination. The male litter continued to receive exposure up to 30 or 90 days after birth. The effects of chronic exposure on GSH levels, transsulfuration pathway enzymatic activity, expression of cysteine/cystine transporters, glutamate transporters, and ionotropic glutamate receptor subunits as well as behavioral performance in the object recognition memory task were assessed. Combined exposure resulted in a significant reduction in GSH levels in the cortex and hippocampus at different times, decreased transsulfuration pathway enzyme activity, as well as diminished xCT protein expression. Altered glutamate receptor expression in the cortex and hippocampus and decreased transaminase enzyme activity were observed. These molecular alterations were associated with memory impairment in the object recognition task, which relies on these brain regions.

Enhancement of memory consolidation by an avoidance conditioned stimulus: Modulation by the D3 receptor

Conditioned stimuli (CS) paired with foot-shock can enhance memory consolidation. Because the dopamine D3 receptor (D3R) has been implicated in mediating various responses to CSs, the current study explored its potential role in modulation of memory consolidation by an avoidance CS. Male Sprague-Dawley rats trained to avoid foot-shocks in a two-way signalled active avoidance task (8 sessions, 30 trials per session, 0.8 mA foot-shock) were pre-treated with the D3R antagonist NGB-2904 (Vehicle, 0.1 or 5 mg/kg) and exposed to the CS immediately after the sample phase of an object recognition memory task. Discrimination ratios were assessed 72 h later. Immediate, but not delayed (6 h), post-sample exposure to the CS enhanced object recognition memory and this effect was blocked by NGB-2904. Control experiments with the beta-noradrenergic receptor antagonist propranolol (10 or 20 mg/kg) and D2R antagonist pimozide (0.2 or 0.6 mg/kg) indicated that NGB-2904 targeted post-training memory consolidation. Exploring the pharmacological selectivity of the NGB-2904 effect, it was found that: 1) 5 mg/kg NGB-2904 blocked conditioned memory modulation produced by post-sample exposure to a “weak” CS (one day of avoidance training) and concurrent stimulation of catecholamine activity by 10 mg/kg bupropion; and 2) post-sample exposure to a “weak” CS and concurrent administration of the D3R agonist 7-OH-DPAT (1 mg/kg) enhanced consolidation of object memory. Finally, because 5 mg/kg NGB-2904 had no effect on modulation by avoidance training in the presence of foot-shocks, the findings herein support the hypothesis that the D3R plays an important role in modulation of memory consolidation by CSs.

Endocytosis is required for consolidation of pattern-separated memories in the perirhinal cortex.

The ability to separate similar experiences into differentiated representations is proposed to be based on a computational process called pattern separation, and it is one of the key characteristics of episodic memory. Although pattern separation has been mainly studied in the dentate gyrus of the hippocampus, this cognitive function if thought to take place also in other regions of the brain. The perirhinal cortex is important for the acquisition and storage of object memories, and in particular for object memory differentiation. The present study was devoted to investigating the importance of the cellular mechanism of endocytosis for object memory differentiation in the perirhinal cortex and its association with brain-derived neurotrophic factor, which was previously shown to be critical for the pattern separation mechanism in this structure. We used a modified version of the object recognition memory task and intracerebral delivery of a peptide (Tat-P4) into the perirhinal cortex to block endocytosis. We found that endocytosis is necessary for pattern separation in the perirhinal cortex. We also provide evidence from a molecular disconnection experiment that BDNF and endocytosis-related mechanisms interact for memory discrimination in both male and female rats. Our experiments suggest that BDNF and endocytosis are essential for consolidation of separate object memories and a part of a time-restricted, protein synthesis-dependent mechanism of memory stabilization in Prh during storage of object representations.

Spontaneous Object Exploration in a Recessive Gene Knockout Model of Parkinson's Disease: Development and Progression of Object Recognition Memory Deficits in Male Pink1-/- Rats.

Cognitive impairments appear at or before motor signs in about one third of patients with Parkinson's disease (PD) and have a cumulative prevalence of roughly 80% overall. These deficits exact an unrelenting toll on patients' quality and activities of daily life due in part to a lack of available treatments to ameliorate them. This study used three well-validated novel object recognition-based paradigms to explore the suitability of rats with knockout of the PTEN-induced putative kinase1 gene (Pink1) for investigating factors that induce cognitive decline in PD and for testing new ways to mitigate them. Longitudinal testing of rats from 3-9 months of age revealed significant impairments in male Pink1-/- rats compared to wild type controls in Novel Object Recognition, Novel Object Location and Object-in-Place tasks. Task-specific differences in the progression of object discrimination/memory deficits across age were also seen. Finally, testing using an elevated plus maze, a tapered balance beam and a grip strength gauge showed that in all cases recognition memory deficits preceded potentially confounding impacts of gene knockout on affect or motor function. Taken together, these findings suggest that knockout of the Pink1 gene negatively impacts the brain circuits and/or neurochemical systems that support performance in object recognition tasks. Further investigations using Pink1-/- rats and object recognition memory tasks should provide new insights into the neural underpinnings of the visual recognition memory and visuospatial information processing deficits that are often seen in PD patients and accelerate the pace of discovery of better ways to treat them.

Learning differentially increases the synaptic levels of AMPA receptor subunits (GluA1‐GluA4) in the rodent hippocampus: a single‐synapse approach

AbstractBackgroundDecades of experimental work support the idea that synapses are the anatomical substrate for experience‐dependent plasticity in the brain. Changes in the synaptic strength underlie learning and memory via the accumulation of glutamate AMPA receptors (AMPAR) at the surface of excitatory synapses. AMPAR are tetrameric receptors constituted by multiple combination of four subunits: GluA1 GluA2, GluA3, and GluA4. However, the relative contribution of each AMPAR subunit on learning and memory is relatively unexplored.MethodHere, we introduce Fluorescence Analysis of Single‐Synapse Potentiation induced by Learning (FASS‐PiL), a flow cytometry‐based method to quantify surface levels of all four GluA‐AMPAR subunits, in parallel, in isolated synaptosomes after a learning episode in rodents. We evaluated surface levels of all four AMPAR subunits in synaptosomes of mice trained in a learning protocol commonly used for studying episodic memory in the hippocampus (e.g., Object Location Memory (OLM) and Object Recognition Memory (ORM) tasks). Briefly, after exploring novel objects in a novel environment for 10 min, mice were returned to their home cage for 60 min. After hippocampus dissection, synaptosome isolation, and immunostaining, samples were analyzed via flow cytometry.ResultWe first demonstrated that FASS‐PiL is a simple and sensitive method to track all four GluAs at the synaptosome surface (each GluA subunit was paired with the presynaptic marker Neurexin‐1beta to focus on synaptosome particles containing both pre‐ and postsynaptic compartments). Notably, by profiling hundreds of events, our data showed that the OLM training increases the number of hippocampal synaptosomes expressing high levels of GluA1 and GluA2, but not GluA3 and GluA4 (vs control animals).ConclusionOur results indicate that plasticity‐related mechanisms underlying learning are AMPA‐subunit‐specific in hippocampal synapses. Our approach could provide the basis for protocols to study behavioral‐relevant mechanisms of plasticity directly at the synapse, with single‐event resolution.

Chemogenetic modulation of the medial prefrontal cortex regulates resistance to acute stress-induced cognitive impairments.

The medial prefrontal cortex (mPFC) has been implicated in regulating resistance to the effects of acute uncontrollable stress. We previously showed that mPFC-lesioned animals exhibit impaired object recognition memory after acute exposure to a brief stress that had no effect in normal animals. Here, we used designer receptors exclusively activated by designer drugs to determine how modulating mPFC activity affects recognition-memory performance under stressful conditions. Specifically, animals with chemogenetic excitation or inhibition of the mPFC underwent either a brief ineffective stress (20-min restraint + 20 tail shocks) or a prolonged effective stress (60-min restraint + 60 tail shocks). Subsequent recognition memory tests showed that animals with chemogenetic mPFC inhibition exposed to brief stress showed impairment in an object recognition memory task, whereas those with chemogenetic mPFC excitation exposed to prolonged stress did not. Thus, the present findings the decreased mPFC activity exacerbates acute stress effects on memory function whereas increased mPFC activity counters these stress effects provide evidence that the mPFC bidirectionally modulates stress resistance.

Agmatine improves olfactory and cognitive deficits in Spontaneously Hypertensive Rats (SHR): An animal model of Attention Deficit Hyperactivity Disorder (ADHD).

Attention Deficit Hyperactivity Disorder (ADHD) is a highly prevalent and disabling disorder that frequently persists into adulthood. Many patients are considered nonresponders to typical pharmacological treatments due to insufficient symptoms' reduction or the inability to tolerate the side effects of these medications. Agmatine is an endogenous neuromodulator with emotional- and cognitive-enhancing properties that arises as a promising agent to manage several Central Nervous System disorders. Here, we investigated the effects of chronic treatment with agmatine on behavioral impairments exhibited by adult Spontaneously Hypertensive Rats (SHR), an animal model for the study of ADHD. Adult male Wistar and SHR (3-4 months old) received intraperitoneal (i.p.) treatment with saline (NaCl 0.9%) or agmatine (30 mg/kg/day) during 20 consecutive days and were evaluated in a battery of behavioral tasks. Agmatine treatment improved olfactory and recognition memory impairments of SHR evaluated in the olfactory discrimination, object recognition, and social recognition memory tasks. In addition, agmatine administration improved the cognitive flexibility in the water maze test. Agmatine did not alter SHR's locomotor activity and hedonic-like behaviors observed in the open-field and splash tests, respectively. No changes were observed in SHR's systolic blood pressure following agmatine treatment. This study provides the first evidence that agmatine improves olfactory and cognitive impairments observed in an animal model of ADHD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Inhibition of noradrenergic and corticotrophin-releasing factor systems: Effects on enhancement of memory consolidation by unconditioned and conditioned heroin withdrawal

The aim of the current study was to test the hypothesis that unconditioned and conditioned opioid withdrawal enhance memory consolidation through overlapping neural systems. The reported experiments focussed on noradrenaline (NA) and corticotrophin-releasing factor (CRF) because of their known involvement in both opioid withdrawal and memory consolidation. Male Sprague-Dawley rats were implanted with subcutaneous osmotic mini-pumps releasing 3.5 mg/kg/day heroin and received injections of 3 mg/kg naloxone (NLX) to precipitate withdrawal. NLX was preceded by 0.1–0.6 mg/kg lofexidine (LOF) (alpha-2 adrenergic agonist) or 10–20 mg/kg antalarmin (ANT) (CRF1 receptor antagonist), and all injections were administered immediately after (i.e., post-training method) the sample phase of the spontaneous object recognition memory task. The same procedure was repeated 7 days after removal of the mini-pumps. To establish conditioned withdrawal, heroin-exposed rats were confined for 2 h in a context (CS+) following injections of 3 mg/kg NLX and in another context (CS-) following vehicle injections. Seven days after removal of mini-pumps, the effects of immediate post-sample exposure to the CS+ (and CS-) preceded by 0.6 mg/kg LOF or 20 mg/kg ANT were assessed. It was found both LOF and ANT blocked the enhancement of object memory by post-sample NLX administration and by exposure to the CS+. These results suggest that pharmacological and psychological withdrawal impact memory storage by activating overlapping NA and CRF systems.

Low-beta repetitive transcranial magnetic stimulation to human dorsolateral prefrontal cortex during object recognition memory sample presentation, at a task-related frequency observed in local field potentials in homologous macaque cortex, impairs subsequent recollection but not familiarity.

According to dual‐process signal‐detection (DPSD) theories, short‐ and long‐term recognition memory draws upon both familiarity and recollection. It remains unclear how primate prefrontal cortex (PFC) contributes to these processes, but frequency‐specific neuronal activities are considered to play a key role. In Experiment 1, nonhuman primate (NHP) local field potential (LFP) electrophysiological recordings in macaque left dorsolateral PFC (dlPFC) revealed performance‐related differences in a low‐beta frequency range during the sample presentation phase of a visual object recognition memory task. Experiment 2 employed a similar task in humans and targeted left dlPFC (and vertex as a control) with repetitive transcranial magnetic stimulation (rTMS) at 12.5 Hz during occasional sample presentations. This low‐beta frequency rTMS to dlPFC decreased DPSD derived indices of recollection, but not familiarity, in subsequent memory tests of the targeted samples after short delays. The same number of rTMS pulses over the same total duration albeit at a random frequency had no effect on either recollection or familiarity. Neither stimulation protocols had any causal effect upon behaviour when targeted to the control site (vertex). In this study, our hypotheses for our human TMS study were derived from our observations in NHPs; this approach might inspire further translational research through investigation of homologous brain regions and tasks across species using similar neuroscientific methodologies to advance the neural mechanism of recognition memory in primates.

Urocanic acid enhances memory consolidation and reconsolidation in novel object recognition task

Urocanic acid (UCA) is an endogenous small molecule that is elevated in skin, blood and brain after sunlight exposure, mainly playing roles in the periphery systems. Few studies have investigated the role of UCA in the central nervous system. In particular, its role in memory consolidation and reconsolidation is still unclear. In the present study, we investigated the effect of intraperitoneal injection of UCA on memory consolidation and reconsolidation in a novel object recognition memory (ORM) task. In the consolidation version of the ORM task, the protocol involved three phases: habituation, sampling and test. UCA injection immediately after the sampling period enhanced ORM memory performance; UCA injection 6 h after sampling did not affect ORM memory performance. In the reconsolidation version of the ORM task, the protocol involved three phases: sampling, reactivation and test. UCA injection immediately after reactivation enhanced ORM memory performance; UCA injection 6 h after reactivation did not affect ORM memory performance; UCA injection 24 h after sampling without reactivation did not affect ORM memory performance. This UCA-enhanced memory performance was not due to its effects on nonspecific responses such as locomotor activity and exploratory behavior. The results suggest that UCA injection enhances consolidation and reconsolidation of an ORM task, which further extends previous research on UCA effects on learning and memory.

Amyloid-β (25–35) regulates neuronal damage and memory loss via SIRT1/Nrf2 in the cortex of mice

Alzheimer’s disease (AD) is the most common type of dementia. AD is pathologically characterized by synaptic dysfunction and cognitive decline due to the aggregation of a large amount of amyloid-β (Aβ) protein in the brain. However, recent studies have discovered that the Aβ is produced as an antimicrobial peptide that acts against bacteria and viruses. This has renewed interest in the effect of Aβ on AD. Thus, in this study, we investigated the different concentrations of Aβ25–35 on neuroprotection and further explore the related mechanisms. Firstly, we detected the cognitive function using the Y-maze test, novel object recognition memory task and Morris water maze test. Then, we analyzed the ultrastructure of synapses and mitochondria, in addition to evaluating SOD levels. We also examined the effect of Aβ25–35 on the viability and structure of the primary neurons. The western blot analysis was used to measure the protein levels. The results showed that mice treated with high concentration of Aβ25–35 impaired the learning-memory ability and disordered the structure of neurons and mitochondria. Meanwhile, high concentration of Aβ25–35 decreased the SIRT1/Nrf2 related antioxidant capacity and induced apoptosis. In contrast, mice treated with low concentration of Aβ25–35 increased SOD levels and SIRT1/Nrf2 expressions, and induced autophagy. Our data suggest that low concentration of Aβ25–35 may increase SOD levels through SIRT1/Nrf2 and induce autophagy.

Delayed voluntary physical exercise restores “when” and “where” object recognition memory after traumatic brain injury

Physical exercise has been associated with improved cognition and may even reduce memory deficits after brain injuries. The aims of this work were to: 1) assess whether voluntary physical exercise can reduce the deficits associated with traumatic brain injury (TBI) in two different components of episodic-like memory based on object recognition, temporal order memory (“when”), and object location memory (“where”); and 2) determine whether changes in levels of brain-derived neurotrophic factor (BDNF) in the hippocampus and prefrontal cortex, as well as alterations in hippocampal cytokines, insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF), may influence the effects exercise has on either or both tasks. The rats were distributed into a sham group, a TBI group that remained sedentary (TBI-sed), and a TBI group that had access to a running wheel for a 25-day period from post-injury day 11 (TBI-exe). The rats were sacrificed after the “where” memory task, at post-injury day 37. Physical exercise restored the “when” and “where” memories, which had been impaired by the TBI, and increased the concentration of BDNF in the hippocampus, but not the prefrontal cortex. Neither TBI nor exercise were found to significantly affect hippocampal cytokines, IGF-1 or VEGF at this time post-injury. BDNF levels showed significant positive correlations with exercise, and with “when” (but not “where”) memory. These results indicate that post-injury physical exercise restores “when” and “where” object recognition memory tasks after TBI, and that increased BDNF seems to be involved in this effect, particularly with regard to “when” memory.

P.592 Predictors of suicidal ideation and preparative behaviours in subjects with bipolar disorder: the contribution of the chronobiological dis-rhythmicity

Several lines of evidence indicate that anesthetic doses of the non-competitive N-methyl-D-aspartate receptor antagonist ketamine disrupt memory functions in rodents. The mechanism by which anesthetic ketamine produces its adverse behavioural effects is not yet clarified. The implication of nicotinic acetylcholine receptor as a potential site of action of anesthetic ketamine adverse effects on memory is proposed. We investigated the ability of α4β2 nicotinic receptor agonist ABT-418 (0.01, 0.03, 0.1 mg/kg, i.p.) and α7 nicotinic receptor agonist GTS-21 (0.3, 1, 3 mg/kg, i.p.) to counteract recognition memory deficits produced by acute post-training administration of anesthetic ketamine (100 mg/kg, i.p.) in rats. For this purpose, the novel object recognition test, a behavioural paradigm assessing recognition memory abilities in rodents was used. Post-training acute administration of GTS-21 (3 mg/kg) counteracted anesthetic ketamine-induced performance deficits in the novel object recognition memory task. By contrast, ABT-418 failed to reverse the recognition memory deficits caused by anesthetic ketamine. The present findings propose that an α7 nicotinic receptor component might modulate anesthetic ketamine’s adverse effects on recognition memory.

Rats recognize spatial and temporal attributes in a new object recognition memory task with multiple trials

BackgroundEpisodic-like memory tasks based on the spontaneous exploration of objects are commonly applied in one-trial protocols. However, multiple-trial designs are known to reduce animal numbers and data variance, providing faster accumulation of data. New methodIn this study, we devised a new object recognition memory task for rats that carry out multiple trials per session. We developed three types of continual trial tasks: a longer protocol, a shorter protocol, and a protocol in which the experimental session was divided into two days. ResultsIn our design, rats expressed temporal and spatial memory, but not what-where-when content integration. We found that shorter protocols were more efficient to evaluate memory capabilities. Comparison with existing methodsTo the best of our knowledge, it is the first object recognition task with multiple trials that simultaneously assess the temporal and spatial aspects of episodic-like memory. ConclusionsWe suggest that our task is suitable for the simultaneous measurements of brain functions related to spatial and temporal attributes in rats.

Behavioral changes and gene profile alterations after chronic 1,950-MHz radiofrequency exposure: An observation in C57BL/6 mice.

IntroductionDue to public concerns about deleterious biological consequences of radiofrequency electromagnetic fields (RF‐EMF), the potential effects of RF‐EMF on the central nervous system have received wide consideration.MethodsHere, two groups of C57BL/6 mice, aged 2 and 12 months, were exposed to 1,950‐MHz RF‐EMF at a specific absorption rate of 5.0 W/kg for chronic periods (2 hr/day and 5 days/week for 8 months). Behavioral changes were then assessed in the mice at 10 months (sham‐ or RF‐10M) and 20 months (sham‐ or RF‐20M), on the open‐field test, the Y‐maze test, and an object recognition memory task, while biological effects were analyzed via microarray gene profiling of the hippocampus.ResultsOpen‐field test results showed a decrease in the time duration spent at the center while there was a decrease in enhanced memory shown by the Y‐maze test and the novel object recognition test in the RF‐20M mice, compared to sham‐exposed mice, but no significant changes in the RF‐10M group. Based on a 2‐fold change cutoff, the microarray data revealed that 15 genes, which are listed as being involved in neurogenesis on Gene Ontology, were altered in both groups. Quantitative real‐time PCR for validation showed increased expression of Epha8 and Wnt6 in the hippocampi of RF‐20M group mice, although 13 additional genes showed no significant changes following RF‐EMF exposure.ConclusionTherefore, cognitive enhancement following chronic exposure for 8 months to RF‐EMF from middle age may be associated with increases in neurogenesis‐related signals in the hippocampus of C57BL/6 mice.