Lrp8 knockout mice fed a selenium-replete diet display subtle deficits in their spatial learning and memory function.

Selenium is an essential trace element that is delivered to the brain by the selenium transport protein selenoprotein P (SEPP1), primarily by binding to its receptor low-density lipoprotein receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor 2 (ApoER2), at the blood-brain barrier. Selenium transport is required for several important brain functions, with transgenic deletion of either Sepp1 or Lrp8 resulting in severe neurological dysfunction and death in mice fed a selenium-deficient diet. Previous studies have reported that although feeding a standard chow diet can prevent these severe deficits, some motor coordination and cognitive dysfunction remain. Importantly, no single study has directly compared the motor and cognitive performance of the Sepp1 and Lrp8 knockout (KO) lines. Here, we report the results of a comprehensive parallel analysis of the motor and spatial learning and memory function of Sepp1 and Lrp8 knockout mice fed a standard mouse chow diet. Our results revealed that Sepp1 knockout mice raised on a selenium-replete diet displayed motor and cognitive function that was indistinguishable from their wild-type littermates. In contrast, we found that although Lrp8-knockout mice fed a selenium-replete diet had normal motor function, their spatial learning and memory showed subtle deficits. We also found that the deficit in baseline adult hippocampal neurogenesis exhibited by Lrp8-deficit mice could not be rescued by dietary selenium supplementation. Taken together, these findings further highlight the importance of selenium transport in maintaining healthy brain function. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Landmark use by ghost crab (Ocypode quadrata) during wayfinding in a complex maze.

Species of crab have been shown to spatially track and navigate to consequential locations through different processes, such as path integration and landmark orienting. Few investigations examine their ability to wayfind in complex environments, like mazes, with multiple intersections and how they may utilize specific features to benefit this process. Spatial learning potentially would lend a fitness advantage to animals living in complicated habitats, and ghost crab (Ocypode quadrata) is a semiterrestrial species that typically occupies extensive beach environments, which present many navigational challenges. Despite their potential, there are currently no studies that investigate forms of spatial cognition in these animals. To better diversify our knowledge of this trait, the current research exposed ghost crab to a maze with seven intersections. Animals were given multiple trials to learn the location of a reward destination to a specific criterion proficiency. In one condition several landmarks were distributed throughout the maze, and in another the environment was completely empty. Results showed that ghost crab in the landmark present group were able to learn the maze faster, they required significantly fewer trials to reach the learning criterion than those in the landmark absent group. However, only approximately half of the total sample met the learning criterion, indicating the maze was rather difficult. These findings are interpreted through theories of route learning that suggest animals may navigate by establishing landmark-turn associations. Such processes have implications for the cognitive ability of ghost crab, and spatial learning in this species may support the notion of convergent evolution for this trait.

Differentiated somatic gene expression is triggered in the dorsal hippocampus and the anterior retrosplenial cortex by hippocampal synaptic plasticity prompted by spatial content learning.

Hippocampal afferent inputs, terminating on proximal and distal subfields of the cornus ammonis (CA), enable the functional discrimination of 'what' (item identity) and 'where' (spatial location) elements of a spatial representation. This kind of information is supported by structures such as the retrosplenial cortex (RSC). Spatial content learning promotes the expression of hippocampal synaptic plasticity, particularly long-term depression (LTD). In the CA1 region, this is specifically facilitated by the learning of item-place features of a spatial environment. Gene-tagging, by means of time-locked fluorescence in situ hybridization (FISH) to detect nuclear expression of immediate early genes, can reveal neuronal populations that engage in experience-dependent information encoding. In the current study, using FISH, we examined if learning-facilitated LTD results in subfield-specific information encoding in the hippocampus and RSC. Rats engaged in novel exploration of small items during stimulation of Schaffer collateral-CA1 synapses. This resulted in LTD (> 24 h). FISH, to detect nuclear expression of Homer1a, revealed that the distal-CA1 and proximal-CA3 subcompartments were particularly activated by this event. By contrast, all elements of the proximodistal cornus ammonis-axis showed equal nuclear Homer1a expression following LTD induction solely by means of afferent stimulation. The RSC exhibited stronger nuclear Homer1a expression in response to learning-facilitated LTD, and to novel item-place experience, compared to LTD induced by sole afferent stimulation in CA1. These results show that both the cornus ammonis and RSC engage in differentiated information encoding of item-place learning that is salient enough, in its own right, to drive the expression of hippocampal LTD. These results also reveal a novel role of the RSC in item-place learning.

A Ketogenic Diet may Improve Cognitive Function in Rats with Temporal Lobe Epilepsy by Regulating Endoplasmic Reticulum Stress and Synaptic Plasticity.

A ketogenic diet (KD) is often used in the treatment of refractory epilepsy. Many studies have found that it also has a positive impact on cognitive comorbidities, but the specific mechanism remains unclear. In many disease models, endoplasmic reticulum stress (ERS) and synaptic plasticity is considered a new therapeutic target for improving cognitive impairment, and it has become a research focus in recent years. Recently, studies have found that a KD has a certain regulatory effect on both ERS and synaptic plasticity, but this result has not been confirmed in epilepsy. To investigate the effect of a KD on ERS and synaptic plasticity. In this study, a rat model of temporal lobe epilepsy (TLE) induced by lithium chloride-pilocarpine was used. After the model was successfully established, the rats in each group were fed a normal diet or a KD for 28 days, and the effect of a KD on the latency and seizure frequency of spontaneous recurrent seizures (SRSs) was observed via video monitoring. Subsequently, a Morris water maze was used to evaluate the spatial learning and memory abilities of the rats in each group; the ultrastructure of the ER and the synapses of the hippocampus were observed by transmission electron microscopy, and the dendritic spine density of the hippocampus was analysed by Golgi staining. Long-term potentiation (LTP) was used to detect the synaptic plasticity of the rats' hippocampi, and the expression of ERS-related proteins and synapse-related proteins was detected by Western blotting. A KD effectively reduced the frequency of SRSs in rats with TLE and improved their learning and memory impairment. Further investigations found that a KD inhibited the up-regulation of glucose-regulated protein 78, phospho-protein kinase-like ER kinase, phosphorylated α subunit of eukaryotic initiation factor 2, activating transcription factor 4 and C/EBP homologous protein expression in the hippocampi of rats with TLE and protected the ultrastructure of the neuronal ER, suggesting that a KD suppressed excessive ERS induced by epilepsy. Concurrently, we also found that a KD not only improved the synaptic ultrastructure and increased the density of dendritic spines in rats with TLE but also reversed the epilepsy-induced LTP deficit to some extent. More importantly, the expression of postsynaptic density protein 95, synaptotagmin-1 and synaptosomal-associated protein 25 in the hippocampi of rats with epilepsy was significantly increased after KD intervention. The study findings indicate that a KD improves learning and memory impairment in rats with epilepsy, possibly by regulating ERS and synaptic plasticity.

Impact of Sleep Deprivation on the Brain's Inflammatory Response Triggered by Lipopolysaccharide and Its Consequences on Spatial Learning and Memory and Long-Term Potentiation in Male Rats.

INTRODUCTION: Both sleep deprivation (SD) and inflammation can negatively affect cognitive function. This study aimed to investigate how SD impacts the brain's inflammatory response to lipopolysaccharide (LPS) and its subsequent effects on cognitive functions. METHODS: To this end, male rats were tested through a Morris water maze (MWM) to assess their spatial learning and memory. Also, in vivo field potential recordings (to evaluate synaptic plasticity) were done in the Saline, SD, LPS1 (1 mg/kg/7 days), and LPS1+SD groups. Cytokine levels were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Based on the results, the LPS1+SD group showed increased total distance and escape latency compared to the other groups in the MWM test. Besides, the LPS1+SD group exhibited a significant decrease in long-term potentiation (LTP) induction and maintenance in the CA1 area of the brain. Finally, the inflammatory cytokine interleukin-1ß (IL-1ß) levels were significantly higher in the LPS1+SD group than in the Saline group. CONCLUSION: These findings suggest that the combined effects of SD and brain inflammatory response can have more harmful effects on cognitive function, LTP, and inflammatory factors than either SD or LPS1 alone.

Using Appetitive Motivation to Train Mice for Spatial Learning in the Barnes Maze.

The Barnes maze, a well-known spatial-learning paradigm, is based on the innate fear of rodents of large open spaces and their drive to hide. However, additional aversive stimuli (strong light and threatening sounds) are often necessary to provoke the hiding response while rendering the method cumbersome and more stressful. Our objective was to establish a Barnes maze-learning paradigm in mice using palatable food as a reward. After habituating male C57BL6/J or NMRI mice to the reward, the experimenter and the apparatus, either a slow (2 trials/day) or a massive conditioning schedule (4 trials/day), was run. Acquisition training was carried out until mice could locate the reward box with a maximum of one hole error. Then, the box was replaced to another location (reversal phase). Mice needed to relearn the new position with the same criterion. One week later, retention trials were performed. Both strains could reach the learning criteria; in the massive training within a shorter period. Spatial memory was demonstrated in the reversal and retention trials. Our results show that palatable food can be used as an efficient motivator to acquire allocentric navigation in the Barnes maze with the additional advantage of being less stressful.

Entorhinohippocampal cholecystokinin modulates spatial learning by facilitating neuroplasticity of hippocampal CA3-CA1 synapses.

The hippocampus is broadly impacted by neuromodulations. However, how neuropeptides shape the function of the hippocampus and the related spatial learning and memory remains unclear. Here, we discover the crucial role of cholecystokinin (CCK) in heterosynaptic neuromodulation from the medial entorhinal cortex (MEC) to the hippocampus. Systematic knockout of the CCK gene impairs CA3-CA1 LTP and space-related performance. The MEC provides most of the CCK-positive neurons projecting to the hippocampal region, which potentiates CA3-CA1 long-term plasticity heterosynaptically in a frequency- and NMDA receptor (NMDAR)-dependent manner. Selective inhibition of MEC CCKergic neurons or downregulation of their CCK mRNA levels also impairs CA3-CA1 LTP formation and animals' performance in the water maze. This excitatory extrahippocampal projection releases CCK upon high-frequency excitation and is active during animal exploration. Our results reveal the critical role of entorhinal CCKergic projections in bridging intra- and extrahippocampal circuitry at electrophysiological and behavioral levels.

Muscimol inactivation of dorsal striatum in young and aged male rats does not affect paired associates learning performance.

Improving cognitive health for older adults requires understanding the neurobiology of age-related cognitive decline and the mechanisms underlying preserved cognition in old age. During spatial learning tasks, aged humans and rodents shift navigation preferences in favor of a stimulus-response learning strategy. This has been hypothesized to result from competitive interactions of the caudate nucleus/dorsal striatum (DS) memory system with the hippocampus (HPC)-dependent spatial/allocentric memory system. In support of this hypothesis, a recent study reported that inactivation of the DS in aged rodents rescued HPC-dependent spatial learning on a T-maze (Gardner, Gold, & Korol, 2020). Currently, it is unclear whether a shift from HPC-dependent to DS-dependent behavior also contributes to age-related cognitive decline outside of spatial learning and memory. To test the hypothesis that inactivation of the DS can restore age-related cognitive function outside of spatial behavior, the present study bilaterally inactivated the DS of young (n = 8) and aged (n = 7) rats during visuospatial paired associates learning (PAL). This study found that inactivation of the DS did not alter PAL performance in young or aged rats, but did alter a positive control, DS-dependent spatial navigation task. This observation suggests that elevated DS activity does not play a role in the decline of HPC-dependent PAL performance in aged male rats. Given the persistent tendencies of aged rodents toward DS-dependent learning, it will be worthwhile to explore further the coordination dynamics between the HPC and DS that may contribute to age-related cognitive decline. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Inhibition of hippocampal palmitoyl acyltransferase activity impairs spatial learning and memory consolidation.

Protein palmitoylation regulates trafficking, mobilization, localization, interaction, and distribution of proteins through the palmitoyl acyltransferases (PATs) enzymes. Protein palmitoylation controls rapid and dynamic changes of the synaptic architecture that modifies the efficiency and strength of synaptic connections, a fundamental mechanism to generate stable and long-lasting memory traces. Although protein palmitoylation in functional synaptic plasticity has been widely described, its role in learning and memory processes is poorly understood. In this work, we found that PATs inhibition into the hippocampus before and after the training of Morris water maze (MWM) and object location memory (OLM) impaired spatial learning. However, we demonstrated that PATs inhibition during the retrieval does not affect the expression of spatial memory in both MWM and OLM. Accordingly, long-term potentiation induction is impaired by inhibiting PATs into the hippocampus before high-frequency electrical stimulation but not after. These findings suggest that PATs activity is necessary to modify neural plasticity, a mechanism required for memory acquisition and consolidation. Like phosphorylation, active palmitoylation is required to regulate the function of already existing proteins that change synaptic strength in the hippocampus to acquire and later consolidate spatial memories.

Microsaccades as a long-term oculomotor correlate in visual perceptual learning.

Human perceptual learning, experience-induced gains in sensory discrimination, typically yields long-term performance improvements. Recent research revealed long-lasting transfer at the untrained location enabled by feature-based attention (FBA), reminiscent of its global effect (Hung & Carrasco, Scientific Reports, 11(1), 13914, (2021)). Visual Perceptual Learning (VPL) is typically studied while observers maintain fixation, but the role of fixational eye movements is unknown. Microsaccades - the largest of fixational eye movements - provide a continuous, online, physiological measure from the oculomotor system that reveals dynamic processing, which is unavailable from behavioral measures alone. We investigated whether and how microsaccades change after training in an orientation discrimination task. For human observers trained with or without FBA, microsaccade rates were significantly reduced during the response window in both trained and untrained locations and orientations. Critically, consistent with long-term training benefits, this microsaccade-rate reduction persisted over a year. Furthermore, microsaccades were biased toward the target location prior to stimulus onset and were more suppressed for incorrect than correct trials after observers' responses. These findings reveal that fixational eye movements and VPL are tightly coupled and that learning-induced microsaccade changes are long lasting. Thus, microsaccades reflect functional dynamics of the oculomotor system during information encoding, maintenance and readout, and may serve as a reliable long-term physiological correlate in VPL.

An astrocytic signaling loop for frequency-dependent control of dendritic integration and spatial learning.

Dendrites of hippocampal CA1 pyramidal cells amplify clustered glutamatergic input by activation of voltage-gated sodium channels and N-methyl-D-aspartate receptors (NMDARs). NMDAR activity depends on the presence of NMDAR co-agonists such as D-serine, but how co-agonists influence dendritic integration is not well understood. Using combinations of whole-cell patch clamp, iontophoretic glutamate application, two-photon excitation fluorescence microscopy and glutamate uncaging in acute rat and mouse brain slices we found that exogenous D-serine reduced the threshold of dendritic spikes and increased their amplitude. Triggering an astrocytic mechanism controlling endogenous D-serine supply via endocannabinoid receptors (CBRs) also increased dendritic spiking. Unexpectedly, this pathway was activated by pyramidal cell activity primarily in the theta range, which required HCN channels and astrocytic CB1Rs. Therefore, astrocytes close a positive and frequency-dependent feedback loop between pyramidal cell activity and their integration of dendritic input. Its disruption in mice led to an impairment of spatial memory, which demonstrated its behavioral relevance.

Object location learning in mice requires hippocampal somatostatin interneuron activity and is facilitated by mTORC1-mediated long-term potentiation of their excitatory synapses.

Hippocampus-dependent learning and memory originate from long-term synaptic changes in hippocampal networks. The activity of CA1 somatostatin interneurons (SOM-INs) during aversive stimulation is necessary for contextual fear memory formation. In addition, mTORC1-dependent long-term potentiation (LTP) of SOM-IN excitatory input synapses from local pyramidal cells (PC-SOM synapses) contributes to the consolidation of fear motivated spatial and contextual memories. Although, it remains unknown if SOM-IN activity and LTP are necessary and sufficient for novelty motivated spatial episodic memory such as the object location memory, and if so when it is required. Here we use optogenetics to examine whether dorsal CA1 SOM-IN activity and LTP are sufficient to regulate object location memory. First, we found that silencing SOM-INs during object location learning impaired memory. Second, optogenetic induction of PC-SOM synapse LTP (TBSopto) given 30 min before object location training, resulted in facilitation of memory. However, in mice with mTORC1 pathway genetically inactivated in SOM-INs, which blocks PC-SOM synapse LTP, TBSopto failed to facilitate object location memory. Our results indicate that SOM-IN activity is necessary during object location learning and that optogenetic induction of PC-SOM synapse LTP is sufficient to facilitate consolidation of object location memory. Thus, hippocampal somatostatin interneuron activity is required for object location learning, a hippocampus-dependent form of novelty motivated spatial learning that is facilitated by plasticity at PC-SOM synapses.

No influence of mineralocorticoid and glutamatergic NMDA receptor stimulation on spatial learning and memory in individuals with major depression.

BACKGROUND: Major depressive disorder (MDD) is associated with impairments in spatial learning and memory and with altered functioning of central mineralocorticoid receptors (MR) and glutamatergic N-methyl-D-aspartate receptors (NMDA-R). Both receptors are highly expressed in the hippocampus and prefrontal cortex - brain areas that are critical for spatial learning and memory. Here, we examined the effects of separate and combined MR and NMDA-R stimulation on spatial learning and memory in individuals with MDD and healthy controls. METHODS: We used a randomized, double-blind, placebo-controlled between-group study design to examine the effects of separate and combined stimulation of the MR (with 0.4 mg fludrocortisone) and NMDA-R (with 250 mg D-cycloserine) in 116 unmedicated individuals with MDD (mean age: 34.7 ± 13.3 years; 78.4% women) and 116 age-, sex-, and education-matched healthy controls. Participants were randomly assigned to one of four conditions: 1) placebo; 2) MR stimulation; 3) NMDA-R stimulation; and 4) combined MR/NMDA-R stimulation. Three hours after drug administration, spatial learning and memory were assessed using a virtual Morris Water Maze task. RESULTS: Individuals with MDD and healthy controls did not differ in spatial learning and memory performance. Neither separate nor combined MR or NMDA-R stimulation altered measures of spatial performance. CONCLUSION: In this study of relatively young, predominantly female, and unmedicated individuals, we found no effect of MDD and no effect of separate or combined MR and NMDA-R stimulation on spatial learning and memory.

Spatial Learning Drives Rapid Goal Representation in Hippocampal Ripples without Place Field Accumulation or Goal-Oriented Theta Sequences.

The hippocampus is critical for rapid acquisition of many forms of memory, although the circuit-level mechanisms through which the hippocampus rapidly consolidates novel information are unknown. Here, the activity of large ensembles of hippocampal neurons in adult male Long-Evans rats was monitored across a period of rapid spatial learning to assess how the network changes during the initial phases of memory formation and retrieval. In contrast to several reports, the hippocampal network did not display enhanced representation of the goal location via accumulation of place fields or elevated firing rates at the goal. Rather, population activity rates increased globally as a function of experience. These alterations in activity were mirrored in the power of the theta oscillation and in the quality of theta sequences, without preferential encoding of paths to the learned goal location. In contrast, during brief "offline" pauses in movement, representation of a novel goal location emerged rapidly in ripples, preceding other changes in network activity. These data demonstrate that the hippocampal network can facilitate active navigation without enhanced goal representation during periods of active movement, and further indicate that goal representation in hippocampal ripples before movement onset supports subsequent navigation, possibly through activation of downstream cortical networks.SIGNIFICANCE STATEMENT Understanding the mechanisms through which the networks of the brain rapidly assimilate information and use previously learned knowledge are fundamental areas of focus in neuroscience. In particular, the hippocampal circuit is a critical region for rapid formation and use of spatial memory. In this study, several circuit-level features of hippocampal function were quantified while rats performed a spatial navigation task requiring rapid memory formation and use. During periods of active navigation, a general increase in overall network activity is observed during memory acquisition, which plateaus during memory retrieval periods, without specific enhanced representation of the goal location. During pauses in navigation, rapid representation of the distant goal well emerges before either behavioral improvement or changes in online activity.

Potential Molecular Mechanisms of Electroacupuncture With Spatial Learning and Memory Impairment Induced by Chronic Pain on a Rat Model.

BACKGROUND: It is frequently reported that neuropathic pain is associated with abnormalities in brain function and structure as well as cognitive deficits. However, the contributing mechanisms have remained elusive. OBJECTIVES: We aimed to investigate the systemic ultrastructural changes of the peripheral nervous system (PNS) and central nervous system (CNS) in rats with trigeminal neuralgia (TN) induced by cobra venom, as well as the effects and mechanisms of electroacupuncture (EA) and pregabalin (PGB) on TN. STUDY DESIGN: This study used an experimental design in rats. SETTING: The research took place in the laboratory at the Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine. METHODS: Male Sprague-Dawley rats were randomly divided into 4 groups (n = 12/group): cobra venom (CV), PGB, EA, and sham-operated (SHAM). The development of pain-related behaviors and spatial learning and memory abilities were measured using video recordings and Morris water maze tests, respectively. The ultrastructural changes of the PNS and CNS were examined using transmission electron microscopy. We also screened the differentially expressed genes and proteins in the prefrontal cortex  and hippocampus using  ribonucleic acid sequencing and isobaric tag for relative and absolute quantitation techniques, respectively. Data for the behavioral tests and molecular biology were analyzed with a one-way analysis of variance. RESULTS: The rats in the CV group exhibited long-lasting pain-like behaviors, cognitive deficits, and systemic ultrastructural changes. Both EA and PGB alleviated the chronic pain syndrome, but EA also inhibited the chronic pain-induced cognitive dysfunction and restored normal cellular structures, while PGB was associated with no improvements. Transcriptomic and proteomic analyses revealed marcks, pak2 and acat1 were altered in rats with TN but were adjusted back to baseline by EA but not by PGB. LIMITATIONS: We examined systemic ultrastructural alterations at different levels of the nervous system; however, the detailed timeline of the damage process was not explicitly delineated.  Moreover, the current study provides only preliminary evidence for the neurobiological mechanisms of cognitive impairment resulting from chronic pain.  Further research is still necessary (using models such as gene knockout rats and cell cultures) before a detailed mechanism can be postulated. CONCLUSIONS: EA treatment may offer significant advantages when compared to PGB for the treatment of cognitive impairment associated with chronic pain. Moreover, marcks, pak2 and acat1 may be the potential therapeutic targets of EA.

Replays of socially acquired information in the hippocampus.

Replays of place cell sequences in the hippocampus are thought to underlie memory consolidation for spatial learning. In this issue of Neuron, Mou et al. show that not only self-running but also social observation experiences promote awake remote replays for planning future journeys.

The role of the gut microbiota and nutrition on spatial learning and spatial memory: a mini review based on animal studies.

The gut-brain axis is believed to constitute a bidirectional communication mechanism that affects both mental and digestive processes. Recently, the role of the gut microbiota in cognitive performance has been the focus of much research. In this paper, we discuss the effects of gut microbiota and nutrition on spatial memory and learning. Studies have shown the influence of diet on cognitive capabilities such as spatial learning and memory. It has been reported that a high-fat diet can alter gut microbiota which subsequently leads to changes in spatial learning and memory. Some microorganisms in the gut that can significantly affect spatial learning and memory are Akkermansia muciniphila, Bifidobacterium, Lactobacillus, Firmicutes, Bacteroidetes, and Helicobacter pylori. For example, a reduction in the amount of A. muciniphila in the gut leads to increased intestinal permeability and induces immune response in the brain which then negatively affects cognitive performances. We suggest that more studies should be carried out regarding the indirect effects of nutrition on cognitive activities via alteration in gut microbiota.

Influence of diurnal phase on behavioral tests of sensorimotor performance, anxiety, learning and memory in mice.

Behavioral measurements in mice are critical tools used to evaluate the effects of interventions. Whilst mice are nocturnal animals, many studies conduct behavioral tests during the day. To better understand the effects of diurnal rhythm on mouse behaviors, we compared the results from behavioral tests conducted in the active and inactive phases. C57BL/6 mice were used in this study; we focus on sensorimotor performance, anxiety, learning and memory. Overall, our results show mice exhibit slightly higher cutaneous sensitivity, better long-term contextual memory, and a greater active avoidance escape response during the active phase. We did not observe significant differences in motor coordination, anxiety, or spatial learning and memory. Furthermore, apart from the elevated-O-maze, there was no remarkable sex effect among these tests. This study provides information on the effects of different diurnal phases on types of behavior and demonstrates the importance of the circadian cycle on learning and memory. Although we did not detect differences in anxiety and spatial learning/memory, diurnal rhythm may interact with other factors to influence these behaviors.

Parallel processing of sensory cue and spatial information in the dentate gyrus.

During exploration, animals form an internal map of an environment by combining information about landmarks and the animal's movement, a process that depends on the hippocampus. The dentate gyrus (DG) is the first stage of the hippocampal circuit where self-motion ("where") and sensory cue information ("what") are integrated, but it remains unknown how DG neurons encode this information during cognitive map formation. Using two-photon calcium imaging in mice running on a treadmill along with online cue manipulation, we identify robust sensory cue responses in DG granule cells. Cue cell responses are stable, stimulus-specific, and accompanied by inhibition of nearby neurons. This demonstrates the existence of "cue cells" in addition to better characterized "place cells" in the DG. We hypothesize that the DG supports parallel channels of spatial and non-spatial information that contribute distinctly to downstream computations and affect roles of the DG in spatial navigation and episodic memory.

Age-related cognitive decline in spatial learning and memory of C57BL/6J mice.

During the last decades, most of the preclinical neurodegenerative research was performed in mouse models of amyloidosis, tauopathies or α-synucleinopathies preferentially maintained on a C57BL/6J background. However, comprehensive neurobehavioural data from C57BL/6J mice outlining the critical point of spontaneous cognitive decline are incomplete. In this study, we aimed for the neurobehavioural phenotyping of hippocampus-dependent spatial learning and memory of aging C57BL/6J mice. Neurobehavioural phenotyping was performed by means of a Morris Water Maze (MWM) and a Novel Object Recognition (NOR) test. MWM measurements revealed signs of age-related memory loss in C57BL/6J animals from the age of 6 months onward. The NOR assessment strengthened latter finding by decreasing discrimination indexes (DI) and recognition indexes (RI) starting from the age of 6 months. Taken together, these findings contribute to the current knowledge of spontaneous cognitive behaviours of this perhaps most widely used mouse strain and serve as a benchmark for dementia mouse models to distinguish spontaneous from pathological neurodegenerative behaviour.