Stereotypical Hippocampal Clustering Predicts Navigational Success in Virtualized Real-World Environments.

Structural differences along the hippocampal long axis are believed to underlie meaningful functional differences. Yet, recent data-driven parcellations of the hippocampus subdivide the hippocampus into a 10-cluster map with anterior-medial, anterior-lateral, and posteroanterior-lateral, middle, and posterior components. We tested whether task and experience could modulate this clustering using a spatial learning experiment where male and female participants were trained to virtually navigate a novel neighborhood in a Google Street View-like environment. Participants were scanned while navigating routes early in training and after a 2 week training period. Using the 10-cluster map as the ideal template, we found that participants who eventually learn the neighborhood well have hippocampal cluster maps consistent with the ideal-even on their second day of learning-and their cluster mappings do not deviate over the 2 week training period. However, participants who eventually learn the neighborhood poorly begin with hippocampal cluster maps inconsistent with the ideal template, though their cluster mappings may become more stereotypical after the 2 week training. Interestingly this improvement seems to be route specific: after some early improvement, when a new route is navigated, participants' hippocampal maps revert back to less stereotypical organization. We conclude that hippocampal clustering is not dependent solely on anatomical structure and instead is driven by a combination of anatomy, task, and, importantly, experience. Nonetheless, while hippocampal clustering can change with experience, efficient navigation depends on functional hippocampal activity clustering in a stereotypical manner, highlighting optimal divisions of processing along the hippocampal anterior-posterior and medial-lateral axes.

Loss of CaV1.3 RNA editing enhances mouse hippocampal plasticity, learning, and memory.

L-type CaV1.3 calcium channels are expressed on the dendrites and soma of neurons, and there is a paucity of information about its role in hippocampal plasticity. Here, by genetic targeting to ablate CaV1.3 RNA editing, we demonstrate that unedited CaV1.3ΔECS mice exhibited improved learning and enhanced long-term memory, supporting a functional role of RNA editing in behavior. Significantly, the editing paradox that functional recoding of CaV1.3 RNA editing sites slows Ca2+-dependent inactivation to increase Ca2+ influx but reduces channel open probability to decrease Ca2+ influx was resolved. Mechanistically, using hippocampal slice recordings, we provide evidence that unedited CaV1.3 channels permitted larger Ca2+ influx into the hippocampal pyramidal neurons to bolster neuronal excitability, synaptic transmission, late long-term potentiation, and increased dendritic arborization. Of note, RNA editing of the CaV1.3 IQ-domain was found to be evolutionarily conserved in mammals, which lends support to the importance of the functional recoding of the CaV1.3 channel in brain function.

Cognitive Flexibility Is Selectively Impaired by Radiation and Is Associated with Differential Recruitment of Adult-Born Neurons.

Exposure to elevated doses of ionizing radiation, such as those in therapeutic procedures, catastrophic accidents, or space exploration, increases the risk of cognitive dysfunction. The full range of radiation-induced cognitive deficits is unknown, partly because commonly used tests may be insufficiently sensitive or may not be adequately tuned for assessing the fine behavioral features affected by radiation. Here, we asked whether γ-radiation might affect learning, memory, and the overall ability to adapt behavior to cope with a challenging environment (cognitive/behavioral flexibility). We developed a new behavioral assay, the context discrimination Morris water maze (cdMWM) task, which is hippocampus-dependent and requires the integration of various contextual cues and the adjustment of search strategies. We exposed male mice to 1 or 5 Gy of γ rays and, at different time points after irradiation, trained them consecutively in spatial MWM, reversal MWM, and cdMWM tasks, and assessed their learning, navigational search strategies, and memory. Mice exposed to 5 Gy performed successfully in the spatial and reversal MWM tasks; however, in the cdMWM task 6 or 8 weeks (but not 3 weeks) after irradiation, they demonstrated transient learning deficit, decreased use of efficient spatially precise search strategies during learning, and, 6 weeks after irradiation, memory deficit. We also observed impaired neurogenesis after irradiation and selective activation of 12-week-old newborn neurons by specific components of cdMWM training paradigm. Thus, our new behavioral paradigm reveals the effects of γ-radiation on cognitive flexibility and indicates an extended timeframe for the functional maturation of new hippocampal neurons.SIGNIFICANCE STATEMENT Exposure to radiation can affect cognitive performance and cognitive flexibility - the ability to adapt to changed circumstances and demands. The full range of consequences of irradiation on cognitive flexibility is unknown, partly because of a lack of suitable models. Here, we developed a new behavioral task requiring mice to combine various types of cues and strategies to find a correct solution. We show that animals exposed to γ-radiation, despite being able to successfully solve standard problems, show delayed learning, deficient memory, and diminished use of efficient navigation patterns in circumstances requiring adjustments of previously used search strategies. This new task could be applied in other settings for assessing the cognitive changes induced by aging, trauma, or disease.

Indispensable role of Nectin-like 4 in regulating synapse-related molecules, synaptic structure, and individual behavior.

Nectin-like family members (Necls) are involved in synaptic organization. In contrast to that of Necl-2/CADM1/SynCAM1, which is critical in synaptic events, investigation of Necl-4/CADM4/SynCAM4 in synapses has largely lagged behind given the particularity of homophilic self-interactions compared to interactions with other Necls. We sought to further understand the role of Necl-4 in synapses and found that knockout of Necl-4 led to aberrant expression levels of proteins mediating synaptic function in cortex homogenates and augmented accumulation of ionotropic glutamate receptor in postsynaptic density fractions, although a compensatory effect of Necl-1 on the expression levels existed. Concurrently, we also found increased synaptic clefts in the cortex and simplified dendritic morphology of primary cultured cortical neurons. Experiments on individual behaviors suggested that compared to their wild-type littermates, Necl-4-KO mice exhibited impaired acquisition of spatial memory and working memory and enhanced behavioral despair and anxiety-like behavior. These findings suggest that Necl-4 mediates synaptic function and related behaviors through an indispensable role and offer a new perspective about collaboration and specialization among Necls.

The effects of estrogens on spatial learning and memory in female rodents - A systematic review and meta-analysis.

Estrogens have inconsistent effects on learning and memory in both the clinical and preclinical literature. Preclinical literature has the advantage of investigating an array of potentially important factors contributing to the varied effects of estrogens on learning and memory, with stringently controlled studies. This study set out to identify specific factors in the animal literature that influence the effects of estrogens on cognition, for possible translation back to clinical practice. The literature was screened and studies meeting strict inclusion criteria were included in the analysis. Eligible studies included female ovariectomized rodents with an adequate vehicle for the estrogen treatment, with an outcome of spatial learning and memory in the Morris water maze. Training days of the Morris water maze were used to assess acquisition of spatial learning, and the probe trial was used to evaluate spatial memory recall. Continuous outcomes were pooled using a random effects inverse variance method and reported as standardized mean differences with 95 % confidence intervals. Subgroup analyses were developed a priori to assess important factors. The overall analysis favoured treatment for the later stages of training and for the probe trial. Factors including the type of estrogen, route, schedule of administration, age of animals, timing relative to ovariectomy, and duration of treatment were all found to be important. The subgroup analyses showed that chronic treatment with 17ß-estradiol, either cyclically or continuously, to young animals improved spatial recall. These results, observed in animals, can inform and guide further clinical research on hormone replacement therapy for cognitive benefits.

Effects of exercise-targeted hippocampal PDE-4 methylation on synaptic plasticity and spatial learning/memory impairments in D-galactose-induced aging rats.

Physical exercise reduces the effects of aging and cognitive decline by improving synaptic plasticity and spatial learning. However, the underlying neurobiological mechanisms are unclear. A total of 45 Male SPF Sprague-Dawley rats were acclimatized and then allocated into three groups, 15 in each group: the saline control (DC) group, D-gal-induced aging (DA) group, and D-gal-induced aging + exercise (DE) group. Six weeks of intraperitoneal injections of D-gal at a concentration of 100 mg/kg body weight/d was injected to establish model of aging in the DA and DE groups. Morris water maze test was implemented to evaluate the hippocampus related cognition. SOD activity and MDA was tested to assess the aging in all groups. H&E and Nissl staining was used to observe the histopathological changes of hippocampal neurons in aging rats. Quantitative real-time polymerase chain reaction, western blotting and immunofluorescence staining techniques were used to investigate the expression of synaptic genes and proteins in the hippocampus. Massarray methylation system was employed to measure the PDE-4 gene methylation level in rat hippocampal tissues. Our results demonstrated that exercise intervention improves cognitive function in D-gal-induced aging rats. The methylation of CpG sites in PDE-4 in the hippocampus was significantly increased. The physical exercise significantly increased PDE-4 gene methylation and effectively decreased PDE-4 gene and protein expression. These beneficial behavioral and morphological effects were attributed to PDE-4 methylation, which was activated cAMP/PKA/CREB pathway and improved synaptic plasticity. Exercise induced PDE-4 methylation is key mechanism underpinning the amelioration of learning/memory impairment, suggesting the potential efficacy of physical exercise training in delaying brain aging.

The therapeutic potential of 1, 25-dihydroxy vitamin D3 on cisplatin-affected neurological functions is associated with the regulation of oxidative stress and inflammatory markers as well as levels of MMP2/9.

Calcitriol as a biologically active form of vitamin D3 has beneficial effects on all body systems. This vitamin has a potent neuroprotective effect via several independent mechanisms against brain insults induced by anticancer drugs. The present study was designed to examine the neuroprotective effects of calcitriol against neurotoxicity induced by cisplatin. Induction of neurotoxicity was done with cisplatin administration (5 mg/kg/week) for 5 successive weeks in male Wistar rats. The neuroprotective influence of calcitriol supplementation (100ng/kg/day for 5 weeks) was assessed through behavioral, electrophysiological, and molecular experiments. Cisplatin administration impaired spatial learning and memory and decreased prefrontal brain-derived neurotrophic factor (BDNF). Peripheral sensory neuropathy was induced through cisplatin administration. Cisplatin also reduced the amplitudes of the compound action potential of sensory nerves in electrophysiological studies. Cisplatin treatment elevated MDA levels and reduced anti-oxidant (SOD and GPx) enzymes. Pro-inflammatory cytokines (IL-1ß and TNF-α) and metalloproteinase-2 and 9 (MMP-2/9) were augmented through treatment with cisplatin. Learning and memory impairments along with BDNF changes caused by cisplatin were amended with calcitriol supplementation. Reduced sensory nerve conduction velocity in the cisplatin-treated group was improved by calcitriol. Calcitriol partially improved redox imbalance and diminished the pro-inflammatory cytokines and MMP-2/9 levels. Our findings showed that calcitriol supplementation can relieve cisplatin-induced peripheral neurotoxicity. Calcitriol can be regarded as a promising new neuroprotective agent.

"Visualization matters" - stereoscopic visualization of 3D graphic neuroanatomic models through AnaVu enhances basic recall and radiologic anatomy learning when compared with monoscopy.

BACKGROUND: The authors had previously developed AnaVu, a low-resource 3D visualization tool for stereoscopic/monoscopic projection of 3D models generated from pre-segmented MRI neuroimaging data. However, its utility in neuroanatomical education compared to conventional methods (specifically whether the stereoscopic or monoscopic mode is more effective) is still unclear. METHODS: A three-limb randomized controlled trial was designed. A sample (n = 152) from the 2022 cohort of MBBS students at Government Medical College, Thiruvananthapuram (GMCT), was randomly selected from those who gave informed consent. After a one-hour introductory lecture on brainstem anatomy and a dissection session, students were randomized to three groups (S - Stereo; M - Mono and C - Control). S was given a 20-min demonstration on the brainstem lesson module in AnaVu in stereoscopic mode. M was given the same demonstration, but in monoscopic mode. The C group was taught using white-board drawn diagrams. Pre-intervention and post-intervention tests for four domains (basic recall, analytical, radiological anatomy and diagram-based questions) were conducted before and after the intervention. Cognitive loads were measured using a pre-validated tool. The groups were then swapped -S→ M, M →S and C→S, and they were asked to compare the modes. RESULTS: For basic recall questions, there was a statistically significant increase in the pre/post-intervention score difference of the S group when compared to the M group [p = 0.03; post hoc analysis, Bonferroni corrections applied] and the C group [p = 0.001; ANOVA test; post hoc analysis, Bonferroni corrections applied]. For radiological anatomy questions, the difference was significantly higher for S compared to C [p < 0.001; ANOVA test; post hoc analysis, Bonferroni corrections applied]. Cognitive load scores showed increased mean germane load for S (33.28 ± 5.35) and M (32.80 ± 7.91) compared with C (28.18 ± 8.17). Subjective feedbacks showed general advantage for S and M compared to C. Out of the S and M swap cohorts, 79/102 preferred S, 13/102 preferred M, and 6/102 preferred both. CONCLUSIONS: AnaVu tool seems to be effective for learning neuroanatomy. The specific advantage seen when taught with stereoscopy in basic recall and radiological anatomy learning shows the importance of how visualization mode influences neuroanatomy learning. Since both S and M are preferred in subjective feedbacks, these results have implications in choosing methods (stereoscopic - needs 3D projectors; monoscopic - needs web based or hand-held devices) to scale AnaVu for anatomy teaching in medical colleges in India. Since stereoscopic projection is technically novel and cost considerations are slightly higher compared to monoscopic projection, the specific advantages and disadvantages of each are relevant in the Indian medical education scenario.

Coercive mating has no impact on spatial learning, cognitive flexibility, and fecundity in female porthole livebearers (Poeciliopsis gracilis).

Coercive mating is a sexual selection strategy that is likely to influence female cognition. Female harassment levels have been linked to altered brain gene expression patterns and brain size evolution, suggesting females may respond to coercive mating by investing energy into "outsmarting" males. However, females exposed to coercive males have decreased foraging efficiency and likely increased stress levels, suggesting their brain function might instead be impaired. While it is therefore likely that coercive mating impacts female cognitive abilities, a direct test of this idea is currently lacking. In this study, we investigate the impact of coercive mating on female spatial memory and cognitive flexibility in a species with prevalent coercive mating. We compared the performance of female porthole livebearers (Poeciliopsis gracilis), which had been previously housed alone or with a coercive male, in both a spatial food localization task and a reversal learning task. While we found that both single and paired fish exhibited high proficiency in learning both tasks, we found no differences in learning ability between females that had or had not experienced coercive mating. In addition, our study found that the presence of a coercive male had no impact on female fecundity, but did influence female mass and standard length. Several studies have assumed that the presence of males, particularly coercive males, may affect the cognitive performance of female fish. However, our study shows that for some species females adapted to coercive mating regimes may be unaffected by male presence with regards to some cognitive tasks.

Neuropharmacological Evidence Implicating Drug-Induced Glutamate Receptor Dysfunction in Affective and Cognitive Sequelae of Subchronic Methamphetamine Self-Administration in Mice.

Methamphetamine (MA) is a highly addictive drug, and MA use disorder is often comorbid with anxiety and cognitive impairment. These comorbid conditions are theorized to reflect glutamate-related neurotoxicity within the frontal cortical regions. However, our prior studies of MA-sensitized mice indicate that subchronic, behaviorally non-contingent MA treatment is sufficient to dysregulate glutamate transmission in mouse brain. Here, we extend this prior work to a mouse model of high-dose oral MA self-administration (0.8, 1.6, or 3.2 g/L; 1 h sessions × 7 days) and show that while female C57BL/6J mice consumed more MA than males, MA-experienced mice of both sexes exhibited some signs of anxiety-like behavior in a behavioral test battery, although not all effects were concentration-dependent. No MA effects were detected for our measures of visually cued spatial navigation, spatial learning, or memory in the Morris water maze; however, females with a history of 3.2 g/L MA exhibited reversal-learning deficits in this task, and mice with a history of 1.6 g/L MA committed more working-memory incorrect errors and relied upon a non-spatial navigation strategy during the radial-arm maze testing. Relative to naïve controls, MA-experienced mice exhibited several changes in the expression of certain glutamate receptor-related proteins and their downstream effectors within the ventral and dorsal areas of the prefrontal cortex, the hippocampus, and the amygdala, many of which were sex-selective. Systemic pretreatment with the mGlu1-negative allosteric modulator JNJ 162596858 reversed the anxiety-like behavior expressed by MA-experienced mice in the marble-burying test, while systemic pretreatment with NMDA or the NMDA antagonist MK-801 bi-directionally affected the MA-induced reversal-learning deficit. Taken together, these data indicate that a relatively brief history of oral MA is sufficient to induce some signs of anxiety-like behavior and cognitive dysfunction during early withdrawal that reflect, at least in part, MA-induced changes in the corticolimbic expression of certain glutamate receptor subtypes of potential relevance to treating symptoms of MA use disorder.

Exposure to Radiofrequency Induces Synaptic Dysfunction in Cortical Neurons Causing Learning and Memory Alteration in Early Postnatal Mice.

The widespread use of wireless communication devices has necessitated unavoidable exposure to radiofrequency electromagnetic fields (RF-EMF). In particular, increasing RF-EMF exposure among children is primarily driven by mobile phone use. Therefore, this study investigated the effects of 1850 MHz RF-EMF exposure at a specific absorption rate of 4.0 W/kg on cortical neurons in mice at postnatal day 28. The results indicated a significant reduction in the number of mushroom-shaped dendritic spines in the prefrontal cortex after daily exposure for 4 weeks. Additionally, prolonged RF-EMF exposure over 9 days led to a gradual decrease in postsynaptic density 95 puncta and inhibited neurite outgrowth in developing cortical neurons. Moreover, the expression levels of genes associated with synapse formation, such as synaptic cell adhesion molecules and cyclin-dependent kinase 5, were reduced in the cerebral cortexes of RF-EMF-exposed mice. Behavioral assessments using the Morris water maze revealed altered spatial learning and memory after the 4-week exposure period. These findings underscore the potential of RF-EMF exposure during childhood to disrupt synaptic function in the cerebral cortex, thereby affecting the developmental stages of the nervous system and potentially influencing later cognitive function.

The Influence of Maternal Hypoxia and Buspirone during Pregnancy on Cognitive Abilities and a Stress Response in Adult Male Offspring.

Spatial learning, memory, and reactivity of the hypothalamic-pituitary-adrenocortical system (HPA axis) were studied in adult male rats, whose mothers during pregnancy were subjected to acute moderate normobaric hypoxia, or repeated injections of buspirone, an agonist of type 1A serotonergic receptors (5HT1A), or their combination. Prenatal treatment with buspirone in rats with prenatal hypoxia impaired learning ability during the first day of 5-day training. A decrease in the effectiveness of long-term memory in comparison with short-term memory was revealed in two groups of rats: prenatal treatment with buspirone in combination with hypoxia and injection of physiological saline without hypoxia. The effectiveness of long-term memory and the level of corticosterone in response to stress did not differ between the groups, which can indicate adaptation of the 5HT1A receptor and the HPA axis to the prenatal buspirone and normobaric hypoxia during ontogeny.

Execution of new trajectories toward a stable goal without a functional hippocampus.

The hippocampus is a critical component of a mammalian spatial navigation system, with the firing sequences of hippocampal place cells during sleep or immobility constituting a "replay" of an animal's past trajectories. A novel spatial navigation task recently revealed that such "replay" sequences of place fields can also prospectively map onto imminent new paths to a goal that occupies a stable location during each session. It was hypothesized that such "prospective replay" sequences may play a causal role in goal-directed navigation. In the present study, we query this putative causal role in finding only minimal effects of muscimol-induced inactivation of the dorsal and intermediate hippocampus on the same spatial navigation task. The concentration of muscimol used demonstrably inhibited hippocampal cell firing in vivo and caused a severe deficit in a hippocampal-dependent "episodic-like" spatial memory task in a watermaze. These findings call into question whether "prospective replay" of an imminent and direct path is actually necessary for its execution in certain navigational tasks.

Silencing hippocampal CA2 reduces behavioral flexibility in spatial learning.

The hippocampus is a key structure involved in learning and remembering spatial information. However, the extent to which hippocampal region CA2 is involved in these processes remains unclear. Here, we show that chronically silencing dorsal CA2 impairs reversal learning in the Morris water maze. After platform relocation, CA2-silenced mice spent more time in the vicinity of the old platform location and less time in the new target quadrant. Accordingly, behavioral strategy analysis revealed increased perseverance in navigating to the old location during the first day and an increased use of non-spatial strategies during the second day of reversal learning. Confirming previous indirect indications, these results demonstrate that CA2 is recruited when mice must flexibly adapt their behavior as task contingencies change. We discuss how these findings can be explained by recent theories of CA2 function and outline testable predictions to understand the underlying neural mechanisms. Demonstrating a direct involvement of CA2 in spatial learning, this work lends further support to the notion that CA2 plays a fundamental role in hippocampal information processing.

Differential effects of acute stress on spatial learning and memory in the open-field tower maze across the female estrous cycle.

The purpose of the present investigation was to test how acute stress and levels of circulating estrogens together influence acquisition and retention of spatial learning, as well as explorative behaviors in female rats. We used the hippocampus-dependent Open-field Tower Maze (OFTM) task to assess acquisition followed by a retention test (reacquisition) that was given 48 h later. Immediately prior to acquisition, experimental rats were exposed to an acute restraint stress and were trained under bright lights. Female rats' estrous cycles were tracked throughout training and testing. Exposure to stress did not affect learning when levels of estrogens were low (i.e., during estrus and metestrus). However, acute stress exposure significantly lowered spatial acquisition of the female rats in the phases with rising levels of estrogens (i.e., during diestrus and proestrus). Furthermore, this stress-induced diminishment during acquisition was evident at the beginning of the retention without any presentation of stress. The present findings provide insight about the interactive relationship between stress and sex hormones on cognitive functions.

Adult-born neurons inhibit developmentally-born neurons during spatial learning.

Ongoing neurogenesis in the dentate gyrus (DG) subregion of the hippocampus results in a heterogenous population of neurons. Immature adult-born neurons (ABNs) have physiological and anatomical properties that may give them a unique role in learning. For example, compared to older granule neurons, they have greater somatic excitability, which could facilitate their recruitment into memory traces. However, recruitment is also likely to depend on interactions with other DG neurons through processes such as lateral inhibition. Immature ABNs target inhibitory interneurons and, compared to older neurons, they receive less GABAergic inhibition. Thus, they may induce lateral inhibition of mature DG neurons while being less susceptible to inhibition themselves. To test this we used a chemogenetic approach to silence immature ABNs as rats learned a spatial water maze task, and measured activity (Fos expression) in ABNs and developmentally-born neurons (DBNs). A retrovirus expressing the inhibitory DREADD receptor, hM4Di, was injected into the dorsal DG of male rats at 6w to infect neurons born in adulthood. Animals were also injected with BrdU to label DBNs or ABNs. DBNs were significantly more active than immature 4-week-old ABNs. Silencing 4-week-old ABNs did not alter learning but it increased activity in DBNs. However, silencing ABNs did not affect activation in other ABNs within the DG. Silencing ABNs also did not alter Fos expression in parvalbumin- and somatostatin-expressing interneurons. Collectively, these results suggest that ABNs may directly inhibit DBN activity during hippocampal-dependent learning, which may be relevant for maintaining sparse hippocampal representations of experienced events.

Investigations on learning and memory function in extended one-generation reproductive toxicity studies - when considered needed and based on what?

To justify investigations on learning and memory (L&M) function in extended one-generation reproductive toxicity studies (EOGRTS; Organization for Economic Co-operation and Development (OECD) test guideline (TG) 443) for registration under Registration, Evaluation, Authorization, and Restriction of Chemical (REACH), the European Chemicals Agency has referred to three publications based on which the Agency concluded that "perturbation of thyroid hormone signaling in offspring affects spatial cognitive abilities (learning and memory)" and "Therefore, it is necessary to conduct spatial learning and memory tests for F1 animals". In this paper, the inclusion of the requested L&M tests in an EOGRTS is challenged. In addition, next to the question on the validity of rodent models in general for testing thyroid hormone-dependent perturbations in brain development, the reliability of the publications specifically relied upon by the agency is questioned as these contain numerous fundamental errors in study methodology, design, and data reporting, provide contradicting results, lack crucial information to validate the results and exclude confounding factors, and finally show no causal relationship. Therefore, in our opinion, these publications cannot be used to substantiate, support, or conclude that decreases in blood thyroid (T4) hormone level on their own would result in impaired L&M in rats and are thus not adequate to use as fundament to ask for L&M testing as part of an EOGRTS.

Use of the sun compass by monocularly occluded homing pigeons in a food localisation task in an outdoor arena.

Functional asymmetries of the avian visual system can be studied in monocularly occluded birds, as their hemispheres are largely independent. Right and left monocularly occluded homing pigeons and control birds under binocular view have been trained in a food localisation task in an octagonal outdoor arena provided with one coloured beacon on each wall. The three groups were tested after the removal of the visual beacons, so to assess their sun compass learning abilities. Pigeons using the left eye/right hemisphere system exhibited slower learning compared to the other monocular group. During the test in the arena void of visual beacons, the three groups of birds, regardless of their visual condition, were generally able to identify the training sector by exclusively relying on sun compass information. However, the directional choices of the pigeons with the left eye/right hemisphere in use were significantly affected by the removal of the beacons, while both control pigeons and birds with the right eye/left hemisphere in use displayed unaltered performances during the test. A subsample of pigeons of each group were re-trained in the octagonal arena with visual beacons present and tested after the removal of visual beacons after a 6 h fast clock-shift treatment. All birds displayed the expected deflection consistent to the sun compass use. While birds using either the left or the right visual systems were equally able to learn a sun compass-mediated spatial task, the left eye/right hemisphere visual system displayed an advantage in relying on visual beacons.

Adding the neuro to cognition: from food storing to nest building.

Typically, investigations of animal cognition couple careful experimental manipulations with examination of the animal's behavioural responses. Sometimes those questions have included attempts to describe the neural underpinnings of the behavioural outputs. Over the past 25 years, behaviours that involve spatial learning and memory (such as navigation and food storing) has been one context in which such dual or correlated investigations have been both accessible and productive. Here I review some of that work and where it has led. Because of the wealth of data and insights gained from that work and song learning before it, it seems that it might also be useful to try to add some neurobiology to other systems in animal cognition. I finish then, with a description of recent work on the cognition and neurobiology of avian nest building. It is still relatively early days but asking questions about the cognition of nest building has already shown both neural correlates of nest building and that learning and memory play a much greater role in this behaviour than previously considered. While it is not yet clear how putting these components together will be synergistic, the examples of song learning and food storing provide encouragement. Perhaps this might be true for other behaviours too?

Prenatal PM2.5 exposure impairs spatial learning and memory in male mice offspring: from transcriptional regulation to neuronal morphogenesis.

BACKGROUND: As one of the environmental risk factors for human health, atmospheric fine particulate matter (PM2.5) contributes to cognitive deterioration in addition to respiratory and cardiovascular injuries. Recently, increasing evidence implicates that PM2.5 inhalation can affect neurological functions in offspring, but the sex-specific outcomes and the underlying biological processes are largely unknown. OBJECTIVES: To observe the influence of prenatal PM2.5 exposure on cognitive performance in offspring, to elucidate the neuronal morphological alterations and possible transcriptional regulation based on mRNA-sequencing (mRNA-Seq) data after birth, and to determine the key components of PM2.5 contributing to the adverse effects. METHODS: Pregnant C57BL/6J mice were exposed to sterile saline or PM2.5 suspension. Morris water maze test was used to assess the cognitive function in weanling offspring. Microscopic observation was applied to detect neuronal morphogenesis in vivo and in vitro. The cortex tissues from male offspring were collected on postnatal days (PNDs) 1, 7, and 21 for mRNA-Seq analysis. The organic and inorganic components of PM2.5 were separated to assess their contributions using primary cultured neurons. RESULTS: Prenatal PM2.5 exposure impaired spatial learning and memory in weanling male mice, but not female mice. The sex-specific outcomes were associated with mRNA expression profiles of the cortex during postnatal critical windows, and the annotations in Gene Ontology (GO) of differentially expressed genes (DEGs) revealed that the exposure persistently disrupted the expression of genes involved in neuronal features in male offspring. Consistently, axonal growth impairment and dendritic complexity reduction were observed. Importantly, Homeobox A5 (Hoxa5), a critical transcription factor regulating all of the neuronal morphogenesis-associated hub genes on PNDs 1, 7, and 21, significantly decreased in the cortex of male offspring following PM2.5 exposure. In addition, both inorganic and organic components were harmful to axonal and dendritic growth, with organic components exhibiting stronger inhibition than inorganic ones. CONCLUSION: Prenatal PM2.5 exposure affected spatial learning and memory in male mice by disrupting Hoxa5-mediated neuronal morphogenesis, and the organic components, including polycyclic aromatic hydrocarbons (PAHs), posed more adverse effects than the inorganic components.