Dominance‐related changes in spatial memory are associated with changes in hippocampal cell proliferation rates in mountain chickadees

It is well established that spatial memory is dependent on the hippocampus in both mammals and birds. As memory capacity can fluctuate on a temporal basis, it is important to understand the mechanisms mediating such changes. It is known that early memory‐dependent experiences in young animals result in hippocampal enlargement and in increased neurogenesis, including cell proliferation and neuron survival. It is less clear, however, whether temporal changes in spatial memory are also associated with changes in hippocampal anatomy and cell proliferation in fully grown and experienced adult animals. In a previous study, we experimentally demonstrated that socially subordinate mountain chickadees (Poecile gambeli) showed inferior spatial memory performance compared to their dominant group mates, in the absence of significant differences in baseline corticosterone levels. Here we investigated whether these differences in memory between dominant and subordinate birds were associated with changes in the hippocampus. Following memory tests, chickadees were injected with 5‐bromo‐2′‐deoxyuridine to label dividing cells and sacrificed 2 days after the injections. We found no significant differences in volume or the total number of neurons in the hippocampal formation between dominant and subordinate chickadees, but subordinate birds had significantly lower cell proliferation rates in the ventricular zone adjacent to both the hippocampus and mesopallium compared to the dominants. Individuals, which performed better on spatial memory tests tended to have higher levels of cell proliferation. These results suggest that social status can affect cell proliferation rates in the ventricular zone and support the hypothesis that neurogenesis might be involved in memory function in adult animals. © 2004 Wiley Periodicals, Inc. J Neurobiol, 2005     

Prolonged moderate elevation of corticosterone does not affect hippocampal anatomy or cell proliferation rates in mountain chickadees (Poecile gambeli)

Chronic stress and corresponding chronic elevations of glucocorticoid hormones have been widely assumed to have deleterious effects on brain anatomy and functions such as learning and memory. In particular, it has been suggested that chronic elevations of glucocorticoid hormones result in death of hippocampal neurons and in reduced rates of hippocampal neurogenesis. It is not clear, however, if any increase in glucocorticoid levels has negative effects on hippocampal anatomy as many animals regularly maintain moderately elevated levels of glucocrticoids over long periods of time under natural energetically demanding conditions. We used unbiased stereological methods to investigate whether mountain chickadees (Poecile gambeli) implanted for 49 days with continuous time-release corticosterone pellets, designed to approximately double the baseline corticosterone levels, differed from placebo-implanted chickadees in their hippocampal anatomy and cell proliferation rates. We found no significant differences between corticosterone and placebo-implanted birds in either telencephalon volume, volume of the hippocampal formation, or the total number of hippocampal neurons. Cell proliferation rates, measured as the total number of BrdU-labeled cells in the ventricular zone adjacent either to the hippocampus or to the mesopallium, were also not significantly different between corticosterone and placebo-implanted chickadees. Our results suggest that prolonged moderate elevation of corticosterone might not provide the suggested deleterious effects on hippocampal anatomy and neurogenesis in food-caching birds and, as we have shown previously, it actually enhances spatial memory.     

Inhibition of cell proliferation in black‐capped chickadees suggests a role for neurogenesis in spatial learning

Following development, the avian brain continues to produce neurons throughout adulthood, which functionally integrate throughout the telencephalon, including the hippocampus. In food‐storing birds like the black‐capped chickadee (Poecile atricapillus), new neurons incorporated into the hippocampus are hypothesized to play a role in spatial learning. Previous results on the relation between hippocampal neurogenesis and spatial learning, however, are correlational. In this study, we experimentally suppressed hippocampal neuronal recruitment and tested for subsequent effects on spatial learning in adult chickadees. After chickadees exhibited significant learning, we treated birds with daily injections of either saline or methylazoxymethanol (MAM), a toxin that suppresses cell proliferation in the brain and monitored subsequent spatial learning. MAM treatment significantly reduced cell proliferation around the lateral ventricles and neuronal recruitment in the hippocampus, measured using the cell birth marker bromodeoxyuridine. MAM‐treated birds performed significantly worse than controls on the spatial learning task 12 days following the initiation of MAM treatment, a time when new neurons would begin functionally integrating into the hippocampus. This difference in learning, however, was limited to a single trial. MAM treatment did not affect any measure of body condition, suggesting learning impairments were not a product of non‐specific adverse effects of MAM. This is the first evidence of a potential causal link between hippocampal neurogenesis and spatial learning in birds. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 74: 1002–1010, 2014     

Seasonal hippocampal plasticity in food-storing birds

Both food-storing behaviour and the hippocampus change annually in food-storing birds. Food storing increases substantially in autumn and winter in chickadees and tits, jays and nutcrackers and nuthatches. The total size of the chickadee hippocampus increases in autumn and winter as does the rate of hippocampal neurogenesis. The hippocampus is necessary for accurate cache retrieval in food-storing birds and is much larger in food-storing birds than in non-storing passerines. It therefore seems probable that seasonal change in caching and seasonal change in the hippocampus are causally related. The peak in recruitment of new neurons into the hippocampus occurs before birds have completed food storing and cache retrieval for the year and may therefore be associated with spacing caches, encoding the spatial locations of caches, or creating a neuronal architecture involved in the recollection of cache sites. The factors controlling hippocampal plasticity in food-storing birds are not well understood. Photoperiodic manipulations that produce change in food-storing behaviour have no effect on either hippocampal size or neuronal recruitment. Available evidence suggests that changes in hippocampal size and neurogenesis may be a consequence of the behavioural and cognitive involvement of the hippocampus in storing and retrieving food.     

Greater hippocampal neuronal recruitment in food-storing than in non-food-storing birds

Previous research has shown heightened recruitment of new neurons to the chickadee hippocampus in the fall. The present study was conducted to determine whether heightened fall recruitment is associated with the seasonal onset of food-storing by comparing neurogenesis in chickadees and a non-food-storing species, the house sparrow. Chickadees and house sparrows were captured in the wild in fall and spring and received multiple injections of the cell birth marker bromodeoxyuridine (BrdU). Birds were held in captivity and the level of hippocampal neuron recruitment was assessed after 6 weeks. Chickadees showed significantly more hippocampal neuronal recruitment than house sparrows. We found no seasonal differences in hippocampal neuronal recruitment in either species. In chickadees and in house sparrows, one-third of new cells labeled for BrdU also expressed the mature neuronal protein, NeuN. In a region adjacent to the hippocampus, the hyperpallium apicale, we observed no significant differences in neuronal recruitment between species or between seasons. Hippocampal volume and total neuron number both were greater in spring than in fall in chickadees, but no seasonal differences were observed in house sparrows. Enhanced neuronal recruitment in the hippocampus of food-storing chickadees suggests a degree of neurogenic specialization that may be associated with the spatial memory requirements of food-storing behavior.     

Photoperiodic regulation of food storing and hippocampus volume in black-capped chickadees, Poecile atricapillus

In seasonal environments animals organize their behaviour around annual cycles of resource availability. Wild black-capped chickadees are most likely to hoard food in autumn. At this time of year chickadees are also reported to have a larger hippocampus, a brain area important for spatial memory. This study examined how photoperiodic condition affects these seasonal changes. Captive chickadees were exposed to one of three treatments. Photorefractory birds were held on long days (19:5 h light:dark) and had small gonads. Photosensitive birds were held on short days (LD 9:15 h) and also had small gonads. Photostimulated birds were switched from short to long days and quickly entered breeding condition with large gonads. Photosensitive birds (on short days) stored more seeds than photorefractory birds (on long days). Photostimulated birds stored seeds at a high rate when on short days, but reduced storing when transferred to long days. These results indicate that long days inhibit storing regardless of gonadal condition. There were no differences between groups in hippocampal volume, indicating that photoperiod can produce changes in food-storing behaviour without affecting hippocampal size. Copyright 2003 Published by Elsevier Science Ltd on behalf of The Association for the Study of Animal Behaviour.     

Captivity reduces hippocampal volume but not survival of new cells in a food‐storing bird

In many naturalistic studies of the hippocampus wild animals are held in captivity. To test if captivity itself affects hippocampal integrity, adult black‐capped chickadees (Poecile atricapilla) were caught in the fall, injected with bromodeoxyuridine to mark neurogenesis, and alternately released to the wild or held in captivity. The wild birds were recaptured after 4–6 weeks and perfused simultaneously with their captive counterparts. The hippocampus of captive birds was 23% smaller than wild birds, with no hemispheric differences in volume within groups. Between groups there was no statistically significant difference in the size of the telencephalon, or in the number and density of surviving new cells. Proximate causes of the reduced hippocampal volume could include stress, lack of exercise, diminished social interaction, or limited caching opportunity—a hippocampal‐dependent activity. The results suggest the avian hippocampus—a structure essential for rapid, complex relational and spatial learning—is both plastic and sensitive, much as in mammals, including humans. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009     

The relationship between dominance, corticosterone, memory, and food caching in mountain chickadees (Poecile gambeli)

It has been hypothesized that in avian social groups subordinate individuals should maintain more energy reserves than dominants, as an insurance against increased perceived risk of starvation. Subordinates might also have elevated baseline corticosterone levels because corticosterone is known to facilitate fattening in birds. Recent experiments showed that moderately elevated corticosterone levels resulting from unpredictable food supply are correlated with enhanced cache retrieval efficiency and more accurate performance on a spatial memory task. Given the correlation between corticosterone and memory, a further prediction is that subordinates might be more efficient at cache retrieval and show more accurate performance on spatial memory tasks. We tested these predictions in dominant-subordinate pairs of mountain chickadees (Poecile gambeli). Each pair was housed in the same cage but caching behavior was tested individually in an adjacent aviary to avoid the confounding effects of small spaces in which birds could unnaturally and directly influence each other's behavior. In sharp contrast to our hypothesis, we found that subordinate chickadees cached less food, showed less efficient cache retrieval, and performed significantly worse on the spatial memory task than dominants. Although the behavioral differences could have resulted from social stress of subordination, and dominant birds reached significantly higher levels of corticosterone during their response to acute stress compared to subordinates, there were no significant differences between dominants and subordinates in baseline levels or in the pattern of adrenocortical stress response. We find no evidence, therefore, to support the hypothesis that subordinate mountain chickadees maintain elevated baseline corticosterone levels whereas lower caching rates and inferior cache retrieval efficiency might contribute to reduced survival of subordinates commonly found in food-caching parids.     

The effect of environmental harshness on neurogenesis: a large-scale comparison

Harsh environmental conditions may produce strong selection pressure on traits, such as memory, that may enhance fitness. Enhanced memory may be crucial for survival in animals that use memory to find food and, thus, particularly important in environments where food sources may be unpredictable. For example, animals that cache and later retrieve their food may exhibit enhanced spatial memory in harsh environments compared with those in mild environments. One way that selection may enhance memory is via the hippocampus, a brain region involved in spatial memory. In a previous study, we established a positive relationship between environmental severity and hippocampal morphology in food-caching black-capped chickadees (Poecile atricapillus). Here, we expanded upon this previous work to investigate the relationship between environmental harshness and neurogenesis, a process that may support hippocampal cytoarchitecture. We report a significant and positive relationship between the degree of environmental harshness across several populations over a large geographic area and (1) the total number of immature hippocampal neurons, (2) the number of immature neurons relative to the hippocampal volume, and (3) the number of immature neurons relative to the total number of hippocampal neurons. Our results suggest that hippocampal neurogenesis may play an important role in environments where increased reliance on memory for cache recovery is critical.     

No effect of social group composition or size on hippocampal formation morphology and neurogenesis in mountain chickadees (Poecile gambeli)

Brain plasticity and adult neurogenesis may play a role in many ecologically important processes including mate recognition, song learning and production, and spatial memory processing. In a number of species, both physical and social environments appear to influence attributes (e.g., volume, neuron number, and neurogenesis) of particular brain regions. The hippocampus in particular is well known to be especially sensitive to such changes. Although social grouping in many taxa includes the formation of male and female pairs, most studies of the relationship between social environment and the hippocampus have typically considered only solitary animals and those living in same‐sex groups. Thus, the aim of this study was to compare the volume of the hippocampal formation, the total number of hippocampal neurons, and the number of immature neurons in the hippocampus (as determined by doublecortin expression) in mountain chickadees (Poecile gambeli) housed in groups of males and females, male–female pairs, same sex pairs of either males or females, and as solitary individuals. The different groups were visually and physically, but not acoustically, isolated from each other. We found no significant differences between any of our groups in hippocampal volume, the total number of hippocampal neurons, or the number of immature neurons. Our results thus provided no support to the hypothesis that social group composition and/or size have an effect on hippocampal morphology and neurogenesis. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70:538–547, 2010     

Population genetic structure and its implications for adaptive variation in memory and the hippocampus on a continental scale in food-caching black-capped chickadees

Food-caching birds rely on stored food to survive the winter, and spatial memory has been shown to be critical in successful cache recovery. Both spatial memory and the hippocampus, an area of the brain involved in spatial memory, exhibit significant geographic variation linked to climate-based environmental harshness and the potential reliance on food caches for survival. Such geographic variation has been suggested to have a heritable basis associated with differential selection. Here, we ask whether population genetic differentiation and potential isolation among multiple populations of food-caching black-capped chickadees is associated with differences in memory and hippocampal morphology by exploring population genetic structure within and among groups of populations that are divergent to different degrees in hippocampal morphology. Using mitochondrial DNA and 583 AFLP loci, we found that population divergence in hippocampal morphology is not significantly associated with neutral genetic divergence or geographic distance, but instead is significantly associated with differences in winter climate. These results are consistent with variation in a history of natural selection on memory and hippocampal morphology that creates and maintains differences in these traits regardless of population genetic structure and likely associated gene flow.     

Changes in spatial memory mediated by experimental variation in food supply do not affect hippocampal anatomy in mountain chickadees (Poecile gambeli)

Earlier reports suggested that seasonal variation in food-caching behavior (caching intensity and cache retrieval accuracy) might correlate with morphological changes in the hippocampal formation, a brain structure thought to play a role in remembering cache locations. We demonstrated that changes in cache retrieval accuracy can also be triggered by experimental variation in food supply: captive mountain chickadees (Poecile gambeli) maintained on limited and unpredictable food supply were more accurate at recovering their caches and performed better on spatial memory tests than birds maintained on ad libitum food. In this study, we investigated whether these two treatment groups also differed in the volume and neuron number of the hippocampal formation. If variation in memory for food caches correlates with hippocampal size, then our birds with enhanced cache recovery and spatial memory performance should have larger hippocampal volumes and total neuron numbers. Contrary to this prediction we found no significant differences in volume or total neuron number of the hippocampal formation between the two treatment groups. Our results therefore indicate that changes in food-caching behavior and spatial memory performance, as mediated by experimental variations in food supply, are not necessarily accompanied by morphological changes in volume or neuron number of the hippocampal formation in fully developed, experienced food-caching birds.     

Aggravation of chronic stress effects on hippocampal neurogenesis and spatial memory in LPA₁ receptor knockout mice

Background

The lysophosphatidic acid LPA₁ receptor regulates plasticity and neurogenesis in the adult hippocampus. Here, we studied whether absence of the LPA₁ receptor modulated the detrimental effects of chronic stress on hippocampal neurogenesis and spatial memory.

Methodology/Principal Findings

Male LPA₁-null (NULL) and wild-type (WT) mice were assigned to control or chronic stress conditions (21 days of restraint, 3 h/day). Immunohistochemistry for bromodeoxyuridine and endogenous markers was performed to examine hippocampal cell proliferation, survival, number and maturation of young neurons, hippocampal structure and apoptosis in the hippocampus. Corticosterone levels were measured in another a separate cohort of mice. Finally, the hole-board test assessed spatial reference and working memory. Under control conditions, NULL mice showed reduced cell proliferation, a defective population of young neurons, reduced hippocampal volume and moderate spatial memory deficits. However, the primary result is that chronic stress impaired hippocampal neurogenesis in NULLs more severely than in WT mice in terms of cell proliferation; apoptosis; the number and maturation of young neurons; and both the volume and neuronal density in the granular zone. Only stressed NULLs presented hypocortisolemia. Moreover, a dramatic deficit in spatial reference memory consolidation was observed in chronically stressed NULL mice, which was in contrast to the minor effect observed in stressed WT mice.

Conclusions/Significance

These results reveal that the absence of the LPA₁ receptor aggravates the chronic stress-induced impairment to hippocampal neurogenesis and its dependent functions. Thus, modulation of the LPA₁ receptor pathway may be of interest with respect to the treatment of stress-induced hippocampal pathology.     

Variation in memory and the hippocampus across populations from different climates: a common garden approach

Selection for enhanced cognitive traits is hypothesized to produce enhancements to brain structures that support those traits. Although numerous studies suggest that this pattern is robust, there are several mechanisms that may produce this association. First, cognitive traits and their neural underpinnings may be fixed as a result of differential selection on cognitive function within specific environments. Second, these relationships may be the product of the selection for plasticity, where differences are produced owing to an individual's experiences in the environment. Alternatively, the relationship may be a complex function of experience, genetics and/or epigenetic effects. Using a well-studied model species (black-capped chickadee, Poecile atricapillus), we have for the first time, to our knowledge, addressed these hypotheses. We found that differences in hippocampal (Hp) neuron number, neurogenesis and spatial memory previously observed in wild chickadees persisted in hand-raised birds from the same populations, even when birds were raised in an identical environment. These findings reject the hypothesis that variation in these traits is owing solely to differences in memory-based experiences in different environments. Moreover, neuron number and neurogenesis were strikingly similar between captive-raised and wild birds from the same populations, further supporting the genetic hypothesis. Hp volume, however, did not differ between the captive-raised populations, yet was very different in their wild counterparts, supporting the experience hypothesis. Our results indicate that the production of some Hp factors may be inherited and largely independent of environmental experiences in adult life, regardless of their magnitude, in animals under high selection pressure for memory, while traits such as volume may be more plastic and modified by the environment.     

Hippocampal learning,memory, and neurogenesis: Effects of sex and estrogens across the lifespan in adults

This article is part of a Special Issue “Estradiol and Cognition”.There are sex differences in hippocampus-dependent cognition and neurogenesis suggesting that sex hormones are involved. Estrogens modulate certain forms of spatial and contextual memory and neurogenesis in the adult female rodent, and to a lesser extent male, hippocampus. This review focuses on the effects of sex and estrogens on hippocampal learning, memory, and neurogenesis in the young and aged adult rodent. We discuss how factors such as the type of estrogen, duration and dose of treatment, timing of treatment, and type of memory influence the effects of estrogens on cognition and neurogenesis. We also address how reproductive experience (pregnancy and mothering) and aging interact with estrogens to modulate hippocampal cognition and neurogenesis in females. Given the evidence that adult hippocampal neurogenesis plays a role in long-term spatial memory and pattern separation, we also discuss the functional implications of regulating neurogenesis in the hippocampus.     

The seasonal hippocampus of food-storing birds

Food storing is seasonal in birds like chickadees, nuthatches and jays, occurring at high levels in fall and winter and low levels in spring and summer. Memory for cache sites is hippocampus dependent in chickadees and both the recruitment of new neurons into the hippocampus and the total size of the hippocampus change seasonally. Unlike seasonal change in the vocal control nuclei of songbirds, however, change in the hippocampus appears not to be controlled by photoperiod. The annual timing of hippocampal neuronal recruitment and change in hippocampal size is quite variable, reaching maximum levels at different times of year in different studies. The amount of food-storing activity by chickadees is known to be influenced by flock dominance structure, energy balance, food availability, and other seasonally varying factors. The variable timing of seasonal change in the hippocampus may indicate that the hippocampus of food-storing birds changes annually in response to change in the intensity of food storing behaviour itself.     

proNGF Inhibits Neurogenesis and Induces Glial Activation in Adult Mouse Dentate Gyrus

Recent studies have shown that the precursor of nerve growth factor (proNGF) is highly elevated in aging brains and in the brains of patients with Alzheimer’s Disease. proNGF accumulates in hippocampus which is an important neurogenic region related to learning and memory. However, it remains unclear whether proNGF has an influence on hippocampal neurogenesis. In this study, we demonstrated that the high-affinity receptor of proNGF, p75 neurotrophic factor (p75NTR), was expressed both on cells undergoing mitosis and postmitotic mature cells in mouse hippocampus. proNGF infusion into adult mouse hippocampus significantly reduced the density of BrdU-incorporating cells and the density of BrdU/Doublecortin double positive cells in the subgranular zone of hippocampus, indicating an inhibitory effect of proNGF on hippocampal neurogenesis. proNGF infusion also induced prominent cell apoptosis and activated residential astrocyte and microglia, which might further impair the hippocampal neurogenesis. These results implied that proNGF played a pivotal role in regulating the hippocampal neurogenesis and might account for the memory deficit and cognitive impairment.     

No latitudinal differences in adrenocortical stress response in wintering black-capped chickadees (Poecile atricapilla)

Birds respond to deterioration in environmental conditions by elevating their corticosterone levels, which can enhance their survival. It is less clear if animals constantly living in energetically challenging environment show similar increases in adrenocortical function. Previous work has demonstrated that under controlled conditions black-capped chickadees (Poecile atricapilla) from northern latitudes cache more food and perform better on spatial memory tasks than their southern conspecifics. As elevated levels of corticosterone have been shown previously to correlate with spatial memory performance in chickadees, this study aimed to investigate whether black-capped chickadees from northern latitudes have elevated baseline levels of corticosterone and/or a stronger adrenocortical stress response than their southern conspecifics, irrespective of their immediate environment. We found no differences between Alaskan and Colorado chickadees maintained under identical conditions for 3 months in either baseline levels of corticosterone or maximum levels of corticosterone achieved during the stress response. Baseline corticosterone levels were negatively correlated with relative body mass across both groups of birds. Our results suggest that the population differences in food catching behavior and spatial memory were not related to differences in corticosterone levels. We conclude that many reported population differences in baseline levels and in strength of adrenocortical stress response may often reflect differences in local environmental conditions rather than population-specific physiological traits.     

Species‐specific injury‐induced cell proliferation in the hippocampus and subventricular zone of food‐storing and nonstoring wild birds

Cells are continuously born and incorporated into the adult hippocampus (HP). Adult neurogenesis might act to increase the total number of cells or replace dead cells. Thus, neurogenesis might be a primary factor in augmenting, maintaining, or even recovering functions. In zebra finches, HP injury increases cell proliferation in the HP and stem cell rich subventricular zone (SVZ). It is unknown what effect injury has on a species dependent upon the HP for survival in the wild. In food‐storing birds, recovery of caches is seasonal, necessary for survival, dependent upon the HP and is concomitant with a peak in HP neurogenesis. During the fall, food‐storing black‐capped chickadees (BCCs) and nonstoring dark‐eyed juncos (DEJs) were captured and given a unilateral penetrating lesion to the HP one day later. On day 3, birds were injected with the mitotic marker 5‐bromo‐2′‐deoxyuridine (BrdU) and perfused on day 10. If unlesioned, more BrdU‐labeled cells were observed in the HP and SVZ of BCCs compared to DEJs, indicating higher innate cell proliferation or incorporation in BCCs. If lesioned, BrdU‐labeled cells increased in the injured HP of both species; however, lesions caused larger increases in DEJs. DEJs also showed increases in BrdU‐labeled cells in the SVZ and contralateral HP. BCCs showed no such increases on day 10. Thus, during the fall food‐storing season, storers showed suppressed injury‐induced cell proliferation and/or reduced survival rates of these new cells compared to nonstorers. These species differences may provide a useful model for isolating factors involved in cellular responses following injury. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2010