T-maze Task Research Articles

Effectiveness of oral administration of peppermint and coriander extracts on cognition in Scopolamine induced rat model of amnesia

Herbs and spices have been shown to be very effective in the management of the neurological disorders. They have neuroprotective actions that prevent the deterioration of the memory and other cognitive functions in the neurological diseases. Peppermint (menthe×piperita, also known as M. balsamea wild) is a hybrid mint, a cross between water mint and spearmint. Peppermint consists of several medicinal components and research was testified safety of consumption of the peppermint. The study compared the memory-boosting and regaining effects of oral administration of peppermint and coriander extracts. 36 male and female Wistar albino rats were assigned into three groups randomly that is control, coriander and peppermint groups, respectively. A control group (n=6) received neither peppermint nor coriander administered (milk was administered). Peppermint group (n=6) received peppermint extract. Coriander group (n=6) received coriander extract. Amnesia rat model was prepared by the administration of as intraperitoneal injection of scopolamine. The R-maze and T-maze tasks was conducted as mentioned in the literature. Mean trials of acquisition is significantly less (P<0.01) in the peppermint group. The number of mean trials of retention is significantly less (P<0.01) in the peppermint group. The mean trials for retention of the coriander group is significantly (P<0.05) less than the peppermint group. The study results support a positive impact of coriander and peppermint on cognition. The study recommends further detailed studies to support the administration of these extracts in the management of neurological diseases that deteriorates cognition.

Longitudinal changes in EEG power, sleep cycles and behaviour in a tau model of neurodegeneration

BackgroundDisturbed sleep is associated with cognitive decline in neurodegenerative diseases such as Alzheimer’s disease (AD) and frontotemporal dementia (FTD). The progressive sequence of how neurodegeneration affects aspects of sleep architecture in conjunction with behavioural changes is not well understood.MethodsWe investigated changes in sleep architecture, spectral power and circadian rhythmicity in the tet-off rTg4510 mouse overexpressing human P301L tau within the same subjects over time. Doxycycline-induced transgene-suppressed rTg4510 mice, tTa carriers and wild-type mice were used as comparators. Spectral power and sleep stages were measured from within the home cage environment using EEG electrodes. In addition, locomotor activity and performance during a T-maze task were measured.ResultsSpectral power in the delta and theta bands showed a time-dependent decrease in rTg4510 mice compared to all other groups. After the initial changes in spectral power, wake during the dark period increased whereas NREM and number of REM sleep bouts decreased in rTg4510 compared to wild-type mice. Home cage locomotor activity in the dark phase significantly increased in rTg4510 compared to wild-type mice by 40 weeks of age. Peak-to-peak circadian rhythm amplitude and performance in the T-maze was impaired throughout the experiment independent of time. At 46 weeks, rTG4510 mice had significant degeneration in the hippocampus and cortex whereas doxycycline-treated rTG4510 mice were protected. Pathology significantly correlated with sleep and EEG outcomes, in addition to locomotor and cognitive measures.ConclusionsWe show that reduced EEG spectral power precedes reductions in sleep and home cage locomotor activity in a mouse model of tauopathy. The data shows increasing mutant tau changes sleep architecture, EEG properties, behaviour and cognition, which suggest tau-related effects on sleep architecture in patients with neurodegenerative diseases.

Propionic acid induces dendritic spine loss by MAPK/ERK signaling and dysregulation of autophagic flux

Propionic acid (PPA) is a short-chain fatty acid that is an important mediator of cellular metabolism. It is also a by-product of human gut enterobacteria and a common food preservative. A recent study found that rats administered with PPA showed autistic-like behaviors like restricted interest, impaired social behavior, and impaired reversal in a T-maze task. This study aimed to identify a link between PPA and autism phenotypes facilitated by signaling mechanisms in hippocampal neurons. Findings indicated autism-like pathogenesis associated with reduced dendritic spines in PPA-treated hippocampal neurons. To uncover the mechanisms underlying this loss, we evaluated autophagic flux, a functional readout of autophagy, using relevant biomedical markers. Results indicated that autophagic flux is impaired in PPA-treated hippocampal neurons. At a molecular level, the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway was activated and autophagic activity was impaired. We also observed that a MAPK inhibitor rescued dendritic spine loss in PPA-treated hippocampal neurons. Taken together, these results suggest a previously unknown link between PPA and autophagy in spine formation regulation in hippocampal neurons via MAPK/ERK signaling. Our results indicate that MAPK/ERK signaling participates in autism pathogenesis by autophagy disruption affecting dendritic spine density. This study may help to elucidate other mechanisms underlying autism and provide a potential strategy for treating ASD-associated pathology.

Adhesion Molecule L1 Agonist Mimetics Protect Against the Pesticide Paraquat-Induced Locomotor Deficits and Biochemical Alterations in Zebrafish.

Besides several endogenous elements, exogenous factors, including exposure to pesticides, have been recognized as putative factors contributing to the onset and development of neurodegenerative diseases, including Parkinson’s disease (PD). Considering the availability, success rate, and limitations associated with the current arsenals to fight PD, there is an unmet need for novel therapeutic interventions. Therefore, based on the previously reported beneficial functions of the L1 cell adhesion molecule, we hypothesized that L1 mimetic compounds may serve to neutralize neurotoxicity triggered by the pesticide paraquat (PQ). In this study, we attempt to use PQ for inducing PD-like pathology and the L1 mimetic compounds phenelzine sulfate (PS) and tacrine (TC) as potential candidates for the amelioration of PD symptoms using zebrafish as a model system. Administration of PQ together with the L1 mimetic compounds PS or TC (250 nM) improved survival of zebrafish larvae, protected them from locomotor deficits, and increased their sensorimotor reflexes. Moreover, application of PQ together with PS (500 nM) or TC (1000 nM) in adult zebrafish counteracted PQ-induced toxicity, maintaining normal locomotor functions and spatial memory in an open field and T-maze task, respectively. Both L1 mimetic compounds prevented reduction in tyrosine hydroxylase and dopamine levels, reduced reactive oxygen species (ROS) generation, protected against impairment of mitochondrial viability, improved the antioxidant enzyme system, and prevented a decrease in ATP levels. Altogether, our findings highlight the beneficial functions of the agonistic L1 mimetics PS and TC by improving several vital cell functions against PQ-triggered neurotoxicity.

Investigating the impact of mobile range electromagnetic radiation on the medial prefrontal cortex of the rat during working memory

Research has been focused on the effects of radiofrequency electromagnetic radiation (RF-EMR) emitted from a mobile phone on general health, especially the nervous system.The purpose of this study was to investigate the impact of RF-EMR on the brain mechanism of rats by recording local field potentials (LFPs) signals during working memory (WM) task.Subjects were exposed to 900 MHz from a dipole antenna daily for three hours. Exposure was applied, first on a short term base (1 week) and then on a long term base (4 weeks). Behavioral parameters were measured weekly while rats performed T-maze tasks in two types of normal and delayed. LFPs signals were simultaneously recorded by implanted microelectrode arrays on the medial prefrontal cortex (mPFC) of rats.Results showed a significant increase (*p < 0.05) in the task completion time of exposed rats which vanished shortly after the end of short term RF-EMR exposure. Before exposure, during correctly performed delayed tasks, an increase (peak) in power changes of theta band (4−12 Hz) was observed. But during correctly performed normal tasks, an increase appeared only by applying RF-EMR exposure. The similarity in power changes pattern of theta band in both types of tasks was observed after long term exposure. Classification accuracy of LFPs in truly done normal and delayed tasks was compared in pre and post-exposure states. Initial classification accuracy was 84.2 % which decreased significantly (*P < 0.05) after exposure.These observations indicated that RF-EMR may cause unusual brain functioning which is temporary at least for short term exposure.

Uncovering the Modulatory Interactions of Brain Networks in Cognition with Central Thalamic Deep Brain Stimulation Using Functional Magnetic Resonance Imaging

Deep brain stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. It acts by altering brain networks and facilitating synaptic plasticity. For enhancing cognitive functions, the central thalamus (CT) has been shown to be a potential DBS target. The network-level mechanisms contributing to the effect exerted by DBS on the CT (CT-DBS) remain unknown. Combining CT-DBS with functional magnetic resonance imaging (fMRI), this study explored brain areas activated while applying CT-DBS in rats, using a newly developed neural probe that was compatible with MRI and could minimize the image distortion and resolve safety issues. Results showed activation of the anterior cingulate cortex, motor cortex, primary and secondary somatosensory cortices, caudate putamen, hypothalamus, thalamus, and hippocampus, suggesting that the corticostriatal, corticolimbic, and thalamocortical brain networks were affected. Behaviorally, the CT-DBS group required a shorter time than sham controls to learn a water-reward lever-pressing task and made more correct choices in a T-maze task. Concurrent with enhanced learning performance, bilateral CT-DBS resulted in alteration in the functional connectivity of brain networks determined by resting-state fMRI. Western blot analyses showed that the protein level of both dopamine D1 and α4-nicotinic acetylcholine receptors was increased, and dopamine D2 receptor was decreased. These data suggest that CT-DBS can enhance cognitive performance as well as brain connectivity through the modulation of synaptic plasticity, such that CT is a target providing high potential for the remediation of acquired cognitive learning and memory disabilities.

Impairment of cost-benefit decision making in morphine-dependent rats is partly mediated via the alteration of BDNF and p-CREB levels in the nucleus accumbens

The ability to choose goals based on decision usefulness or the time required to reach the goals chosen are important aspects of decision making. There is considerable evidence in the literature indicating the fact that drug abuse affects different aspects of cognition. In the current study, we assessed the effects of morphine dependence and its withdrawal on cost-benefit decision making and furthermore the involvement of BDNF and p-CREB in the nucleus accumbens, a key brain area involved in decision making was measured. Different groups of male Wistar rats were trained in an effort-based and/or delay-based form of cost-benefit T-maze decision-making task. Thereafter, the animals were morphine dependent and the percentage of the high reward preference was evaluated. After behavioral tests, the BDNF level, and p-CREB/CREB ratio were measured by Western blot analysis. The results showed that during effort-based but not delay-based decision making, BDNF and p-CREB levels increased. During effort-based decision making in morphine dependent rats, BDNF decreased but there was no significant change in p-CREB. Besides, during delay-based decision making in the morphine dependent group, both BDNF and p-CREB did not show any significant change. These findings revealed that BDNF and p-CREB/CREB ratio in the NAc are essential factors for effort-based but not delay-based decision making. In addition, impairment of effort-based decision making in morphine dependent rats is related to the decrease of BDNF level but not p-CREB/CREB ratio in the NAc. However, delay-based decision making defects in morphine dependent rats did not associate with the change in BDNF and p-CREB levels in the NAc.

Behavioural and pharmacological profiles of zebrafish administrated pyrrolidinyl benzodioxanes and prolinol aryl ethers with high affinity for heteromeric nicotinic acetylcholine receptors.

Prolinol aryl ethers and their rigidified analogues pyrrolidinyl benzodioxanes have a high affinity for mammalian α4β2 nicotinic acetylcholine receptors (nAChRs). Electrophysiological studies have shown that the former are full agonists and the latter partial agonists or antagonists of human α4β2 receptors, but their in vivo effects are unknown. As α4β2 nAChRs play an important role in the cognition and the rewarding effects of nicotine, we tested the effects of two full agonists and one antagonist on spatial learning, memory and attention in zebrafish using a T-maze task and virtual object recognition test (VORT). The effect of a partial agonist in reducing nicotine-induced conditioned place preference (CPP) was also investigated. In comparison with the vehicle alone, the full agonists MCL-11 and MCL-28 induced a significant cognitive enhancement as measured by the reduced running time in the T-maze and increased attention as measured by the increased discrimination index in the VORT. MCL-11 was 882 times more potent than nicotine. The two compounds were characterised by an inverted U-shaped dose-response curve, and their effects were blocked by the co-administration of the antagonist MCL-117, which alone had no effect. The partial agonist MCL-54 induced CPP and had an inverted U-shaped dose-response curve similar to that of nicotine but blocked the reinforcing effect of co-administered nicotine. Binding studies showed that all of the compounds have a higher affinity for heteromeric [3H]-epibatidine receptors than [125I]-αBungarotoxin receptors. MCL-11 was the most selective of heteromeric receptors. These behavioural studies indicate that full agonist prolinol aryl ethers are very active in increasing spatial learning, memory and attention in zebrafish. The benzodioxane partial agonist MCL-54 reduced nicotine-induced CPP, and the benzodioxane antagonist MCL-117 blocked all agonist-induced activities.

ErbB4 Null Mice Display Altered Mesocorticolimbic and Nigrostriatal Dopamine Levels as well as Deficits in Cognitive and Motivational Behaviors.

Natural genetic variants of Neuregulin1 (NRG1) and its cognate receptor ErbB4 are associated with a risk for schizophrenia. Whereas most studies on NRG1-ErbB4 signaling have focused on GABAergic interneurons, ErbB4 is also expressed by midbrain dopaminergic neurons where it modulates extracellular dopamine (DA) levels. Here, we report that extracellular steady-state levels of DA are reduced in the medial prefrontal cortex (mPFC; −65%), hippocampus (−53%) and nucleus accumbens (NAc; −35%), but are elevated in the dorsal striatum (+25%) of ErbB4 knock-out mice (ErbB4 KOs) relative to wild-type controls. This pattern of DA imbalance recapitulates the reported prefrontal cortical reduction and striatal increase of DA levels in schizophrenia patients. Next, we report on a battery of behavioral tasks used to evaluate locomotor, cognitive and motivational behaviors in ErbB4 KOs relative to controls. We found that ErbB4 KOs are hyperactive in a novel open field but not in their familiar home cage, are more sensitive to amphetamine, perform poorly in the T-maze and novel object recognition (NOR) tasks, exhibit reduced spatial learning and memory on the Barnes maze, and perform markedly worse in conditioned place preference (CPP) tasks when associating cued-reward palatable food with location. However, we found that the poor performance of ErbB4 KOs in CPP are likely due to deficits in spatial memory, instead of reward seeking, as ErbB4 KOs are more motivated to work for palatable food rewards. Our findings indicate that ErbB4 signaling affects tonic DA levels and modulates a wide array of behavioral deficits relevant to psychiatric disorders, including schizophrenia.

Modeling awake hippocampal reactivations with model-based bidirectional search.

Hippocampal offline reactivations during reward-based learning, usually categorized as replay events, have been found to be important for performance improvement over time and for memory consolidation. Recent computational work has linked these phenomena to the need to transform reward information into state-action values for decision making and to propagate it to all relevant states of the environment. Nevertheless, it is still unclear whether an integrated reinforcement learning mechanism could account for the variety of awake hippocampal reactivations, including variety in order (forward and reverse reactivated trajectories) and variety in the location where they occur (reward site or decision-point). Here, we present a model-based bidirectional search model which accounts for a variety of hippocampal reactivations. The model combines forward trajectory sampling from current position and backward sampling through prioritized sweeping from states associated with large reward prediction errors until the two trajectories connect. This is repeated until stabilization of state-action values (convergence), which could explain why hippocampal reactivations drastically diminish when the animal's performance stabilizes. Simulations in a multiple T-maze task show that forward reactivations are prominently found at decision-points while backward reactivations are exclusively generated at reward sites. Finally, the model can generate imaginary trajectories that are not allowed to the agent during task performance. We raise some experimental predictions and implications for future studies of the role of the hippocampo-prefronto-striatal network in learning.

Hydrolyzed Fat Formula Increases Brain White Matter in Small for Gestational Age and Appropriate for Gestational Age Neonatal Piglets.

Background: Intrauterine growth restriction is a common cause of small for gestational age (SGA) infants worldwide. SGA infants are deficient in digestive enzymes required for fat digestion and absorption compared to appropriate for gestational age (AGA) infants, putting them at risk for impaired neurocognitive development.Objective: The objective was to determine if a hydrolyzed fat (HF) infant formula containing soy free fatty acids, 2-monoacylglycerolpalmitate, cholesterol, and soy lecithin could increase brain tissue incorporation of essential fatty acids or white matter to enhance brain development in SGA and AGA neonatal piglet models.Methods: Sex-matched, littermate pairs of SGA (0.5–0.9 kg) and AGA (1.2–1.8 kg) 2 days old piglets (N = 60) were randomly assigned to control (CON) or HF formula diets in a 2 × 2 factorial design. On day 14, 24 piglets were used for hippocampal RNA-sequencing; the rest began a spatial learning task. On days 26–29, brain structure was assessed by magnetic resonance imaging (MRI). Cerebellum and hippocampus were analyzed for fatty acid content.Results: SGA piglets grew more slowly than AGA piglets, with no effect of diet on daily weight gain or weight at MRI. HF diet did not affect brain weight. HF diet increased relative volumes of 7 brain regions and white matter (WM) volume in both SGA and AGA piglets. However, HF did not ameliorate SGA total WM integrity deficits. RNA sequencing revealed SGA piglets had increased gene expression of synapse and cell signaling pathways and decreased expression of ribosome pathways in the hippocampus compared to AGA. HF decreased expression of immune response related genes in the hippocampus of AGA and SGA piglets, but did not correct gene expression patterns in SGA piglets. Piglets learned the T-maze task at the same rate, but SGA HF, SGA CON, and AGA HF piglets had more accurate performance than AGA CON piglets on reversal day 2. HF increased arachidonic acid (ARA) percentage in the cerebellum and total ARA in the hippocampus.Conclusions: HF enhanced brain development in the neonatal piglet measured by brain volume and WM volume in specific brain regions; however, more studies are needed to assess long-term outcomes.

Observational learning of a shifting goal location in rats: Impact of distance, observed performance, familiarity, and delay

BackgroundObservational learning allows for learning without direct exposure to danger or energetic demands. This form of learning is seen in humans, other primates, and other species such as rodents. The neurobiology behind social learning has been studied mostly in rats, specifically focusing on social transmission of food preference and fear. However, less is known regarding the neural circuitry behind social learning of a foraging scenario. New MethodThe current study examined observational learning in a working memory Tmaze task. The food location changed daily such that the observing animal had to learn the correct location anew each day. This delineated the time frame when an animal learned by observation, making the phenomenon easier to study. ResultsRats learned the location of a food reward by observing a conspecific. Furthermore, the distance of the rats from the maze affected performance. Additionally, performance was affected by whether the performer made mistakes. This memory could persist for at least five minutes. Lastly, performance was not affected by observer-demonstrator familiarity Comparison with Existing MethodsPrevious rodent foraging studies typically exposed observers to the same behavior over many observation sessions. In this scenario, it is difficult to determine when and how an animal learns through observation. The current task delineates the period of observation in each session, allowing manipulations during the observation period. ConclusionsThe current paradigm allows for repeated examinations of observational learning and provides an alternative method for neurobiological studies of social learning.

Preference for Exercise vs. More Sedentary Reinforcers: Validation of an Animal Model of Tetrabenazine-Induced Anergia.

Physical activities can have intrinsic motivational or reinforcing properties. The choice to engage in voluntary physical activity is undertaken in relation to the selection of other alternatives, such as sedentary behaviors, drugs, or food intake. The mesolimbic dopamine (DA) system plays a critical role in behavioral activation or exertion of effort, and DA antagonism or depletion induces anergia in effort-based decision-making tasks. However, little is known about the neural mechanisms underlying the decision-making processes that establish preferences for sedentary vs. activity-based reinforcers. In the present work with male CD1 mice, we evaluated the effect of tetrabenazine (TBZ), a DA-depleting agent, on a three-choice T-maze task developed to assess preference between reinforcers with different behavioral activation requirements and sensory properties [i.e., a running wheel (RW) vs. sweet pellets or a neutral nonsocial odor]. We also studied the effects of TBZ on the forced swim test (FST), which measures climbing and swimming in a stressful setting, and on anxiety tests [dark-light (DL) box and elevated plus maze (EPM)]. In the three-choice task, TBZ reduced time running in the wheel but increased time spent consuming sucrose, thus indicating reduced activation but relatively intact sucrose reinforcement. The effect of TBZ was not mimicked by motivational manipulations that change the value of the reinforcers, such as making the RW aversive or harder to move, food-restricting the animals, inducing a binge-like eating pattern, or introducing social odors. In the FST, TBZ decreased time climbing (most active behavior) and increased immobility but did not affect anxiety in the DL or EPM. These results indicate that the three-choice T-maze task could be useful for assessing DA modulation of preferences for exercise based on activation and effort requirements, differentiating those effects from changes in preference produced by altering physical requirements, food restriction state, and stress during testing.

Transient neonatal sleep fragmentation results in long-term neuroinflammation and cognitive impairment in a rabbit model

Sleep fragmentation is an increase in sleep-wake transitions without an overall decrease in total sleep time. Sleep fragmentation is well documented during acute and chronic hospitalization and can result in delirium and memory problems in children. Sleep fragmentation is also often noted in neurodevelopmental disorders. However, it is unclear how sleep fragmentation independent of disease affects brain development and function. We hypothesized that acute sleep fragmentation during the neonatal period in otherwise healthy animals would result in neuroinflammation and would be associated with abnormalities in cognitive development. The orbital shaker method was used to fragment sleep for 72 h in postnatal day 3 New Zealand white rabbit kits (fragmentation group). To control for maternal separation, the sham group was separated from the dam and maintained in the same conditions without undergoing sleep fragmentation. A naïve control group remained with the dam. Kits underwent behavioral testing with novel object recognition and spontaneous alternation T-maze tests at 2–3 weeks post-fragmentation and were sacrificed 3–50 days after fragmentation. Sleep fragmentation resulted in acute and chronic changes in microglial morphology in the hippocampus and cortex, and regional differences in mRNA expression of pro- and anti-inflammatory cytokines at 3, 7 and 50 days post-fragmentation. Impaired novel object recognition and a longer latency in T-maze task completion were noted in the fragmented kits. This was in spite of normalization of sleep architecture noted at 2 months of age in these kits. The results indicate that transient neonatal sleep fragmentation results in short-term and long-term immune alterations in the brain, along with diminished performance in cognitive tasks long-term.

Striatal glutamate delta-1 receptor regulates behavioral flexibility and thalamostriatal connectivity

Impaired behavioral flexibility and repetitive behavior is a common phenotype in autism and other neuropsychiatric disorders, but the underlying synaptic mechanisms are poorly understood. The trans-synaptic glutamate delta (GluD)-Cerebellin 1-Neurexin complex, critical for synapse formation/maintenance, represents a vulnerable axis for neuropsychiatric diseases. We have previously found that GluD1 deletion results in reversal learning deficit and repetitive behavior. In this study, we show that selective ablation of GluD1 from the dorsal striatum impairs behavioral flexibility in a water T-maze task. We further found that striatal GluD1 is preferentially found in dendritic shafts, and more frequently associated with thalamic than cortical glutamatergic terminals suggesting localization to projections from the thalamic parafascicular nucleus (Pf). Conditional deletion of GluD1 from the striatum led to a selective loss of thalamic, but not cortical, terminals, and reduced glutamatergic neurotransmission. Optogenetic studies demonstrated functional changes at thalamostriatal synapses from the Pf, but no effect on the corticostriatal system, upon ablation of GluD1 in the dorsal striatum. These studies suggest a novel molecular mechanism by which genetic variations associated with neuropsychiatric disorders may impair behavioral flexibility, and reveal a unique principle by which GluD1 subunit regulates forebrain circuits.

Effect of the King Oyster Culinary-Medicinal Mushroom Pleurotus eryngii (Agaricomycetes) Basidiocarps Powder to Ameliorate Memory and Learning Deficit in Ability in Aβ-Induced Alzheimer's Disease C57BL/6J Mice Model

One of the major causes of Alzheimer's disease (AD) is oxidative stress, which accelerates β-amyloid peptide (AP) plaque and neurofibrillary tangle accumulation in the brain. Pleurotus eryngii is known to be rich in antioxidants, including ergothioneine, adenosine, and polyphenol, which can reduce oxidative stress-related aging. The aim of this study was to investigate the proximate and functional composition of P. eryngii, and evaluate the cognitive effects of low (LPE), medium (MPE), and high (HPE) P. eryngii dosages in an Aβ-induced Alzheimer's disease C57BL/6J mouse model. Mice fed P. eryngii for six weeks showed no adverse effects on body weight gain, food intake efficiency, serum biochemical parameters, and liver and kidney histopathological features. The relative brain weight was significantly lower in Aβ-injected mice (p < 0.05). Further, P. eryngii was shown to delay brain atrophy. Reference memory behavioral tasks showed that LPE, MPE, and HPE significantly decreased escape latency (49-85%) and distance (53-69%, p < 0.05). Probe and T-maze tasks showed that P. eryngii potently ameliorated memory deficit in mice. An AD pathology index analysis showed that P. eryngii significantly decreased levels of brain phosphorylated τ-protein, Aβ plaque deposition, malondialdehyde, and protein carbonyl (p < 0.05). P. eryngii may therefore promote memory and learning capacity in an Aβ-induced AD mouse model.

The Discrete Paired-trial Variable-delay T-maze Task to Assess Working Memory in Mice.

Working memory abnormalities involving the prefrontal cortex (PFC) dramatically contribute to poor functional outcomes in patients with schizophrenia and still represent an unmet therapeutic need. Studies in rodents might provide essential tools to understand the mechanisms underlying PFC-dependent working memory dysfunctions, as well as precious tools for genetic and pharmacological testing. However, proper tests assessing working memory and sensitive to PFC-dependent functions must be used. In this regard, the discrete paired-trial variable-delay T-maze task, equivalent to delayed non-match to sample tasks used in humans, has proved to be an effective paradigm to test PFC-dependent working memory dysfunctions with high predictive validity in human studies.

Lateral entorhinal cortex lesions impair both egocentric and allocentric object–place associations

During navigation, landmark processing is critical either for generating an allocentric-based cognitive map or in facilitating egocentric-based strategies. Increasing evidence from manipulation and single-unit recording studies has highlighted the role of the entorhinal cortex in processing landmarks. In particular, the lateral (LEC) and medial (MEC) sub-regions of the entorhinal cortex have been shown to attend to proximal and distal landmarks, respectively. Recent studies have identified a further dissociation in cue processing between the LEC and MEC based on spatial frames of reference. Neurons in the LEC preferentially encode egocentric cues while those in the MEC encode allocentric cues. In this study, we assessed the impact of disrupting the LEC on landmark-based spatial memory in both egocentric and allocentric reference frames. Animals that received excitotoxic lesions of the LEC were significantly impaired, relative to controls, on both egocentric and allocentric versions of an object–place association task. Notably, LEC lesioned animals performed at chance on the egocentric version but above chance on the allocentric version. There was no significant difference in performance between the two groups on an object recognition and spatial T-maze task. Taken together, these results indicate that the LEC plays a role in feature integration more broadly and in specifically processing spatial information within an egocentric reference frame.

Lesions of the head direction cell system impair direction discrimination.

Previous results suggest that directional information from the head direction cell circuit may inform hippocampal place cell firing when an animal is confronted with visually identical environments. To investigate whether such information might also be essential for spatial behavior, we tested adult, male Lister Hooded rats that had received either bilateral lateral mammillary nuclei (LMN) lesions or sham lesions on a four-way, conditional odor-location discrimination in compartments arranged at 60° to one another. We found that significantly fewer rats in the LMN lesion group were able to learn the task compared to the Sham group. We also found that the extent of the behavioral impairment was highly correlated with the degree of tissue loss in the LMN resulting from the lesion. Animals with LMN lesions were also impaired in a nonmatching-to-sample task in a T maze, and the extent of impairment likewise depended on the extent of the lesion. Performance in the odor-location and T-maze tasks was not affected by tissue loss in the medial mammillary nuclei. Together, these results indicate that the LMN, a key node in the head direction circuit, is critical for solving a spatial task that requires a directional discrimination. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Modulation of Theta-Band Local Field Potential Oscillations Across Brain Networks With Central Thalamic Deep Brain Stimulation to Enhance Spatial Working Memory.

Deep brain stimulation (DBS) is a well-established technique for the treatment of movement and psychiatric disorders through the modulation of neural oscillatory activity and synaptic plasticity. The central thalamus (CT) has been indicated as a potential target for stimulation to enhance memory. However, the mechanisms underlying local field potential (LFP) oscillations and memory enhancement by CT-DBS remain unknown. In this study, we used CT-DBS to investigate the mechanisms underlying the changes in oscillatory communication between the CT and hippocampus, both of which are involved in spatial working memory. Local field potentials (LFPs) were recorded from microelectrode array implanted in the CT, dentate gyrus, cornu ammonis (CA) region 1, and CA region 3. Functional connectivity (FC) strength was assessed by LFP–LFP coherence calculations for these brain regions. In addition, a T-maze behavioral task using a rat model was performed to assess the performance of spatial working memory. In DBS group, our results revealed that theta oscillations significantly increased in the CT and hippocampus compared with that in sham controls. As indicated by coherence, the FC between the CT and hippocampus significantly increased in the theta band after CT-DBS. Moreover, Western blotting showed that the protein expressions of the dopamine D1 and α4-nicotinic acetylcholine receptors were enhanced, whereas that of the dopamine D2 receptor decreased in the DBS group. In conclusion, the use of CT-DBS resulted in elevated theta oscillations, increased FC between the CT and hippocampus, and altered synaptic plasticity in the hippocampus, suggesting that CT-DBS is an effective approach for improving spatial working memory.