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We investigated the role of the septo-hippocampal cholinergic projection in anxiety, spatial novelty preference, and differential reward for low rates of responding (DRL) performance. Cholinergic neurons of the rat medial septum (MS) and the vertical limb of the diagonal band of Broca (VDB) were lesioned using the selective immunotoxin, 192 IgG-saporin. Rats were then tested on several behavioral tests previously shown to be sensitive to either (a) hippocampal lesions or (b) nonselective MS/VDB lesions which target both cholinergic and y-aminobutyric acid (GABA)-ergic projections, or both. Saporin lesions substantially reduced hippocampal cholinergic innervation, resulting in an absence of acetyl cholinesterase staining and markedly reduced choline acetyltransferase activity (mean reduction: 80 ± 5%; range: 50-97%). However, the saporin-lesioned rats did not differ from control rats in any of the behavioral tests. Thus we found no evidence from these lesion studies that the septo-hippocampal cholinergic projection plays an essential role in anxiety, spatial novelty preference, or DRL. [ABSTRACT FROM AUTHOR]

Age-related cognitive impairments are particularly prevalent in forms of learning that require a functionally intact hippocampal formation, such as spatial and declarative learning. However, there is notable heterogeneity in the cognitive abilities of aged subjects. To date, few studies have determined whether age-related impairments on one learning task relate to impairments on different learning tasks that engage overlapping cognitive processes. Here, we hypothesized that aged animals that were impaired on 1 hippocampal-dependent behavioral procedure would be impaired on a second hippocampal-dependent procedure. Conversely, aged animals that were unimpaired on 1 hippocampal-dependent task would be unimpaired with a subsequent hippocampal-dependent form of learning. To test these hypotheses, we trained young (2-3 months old) and aged (28-29 months old) F344XBN male rats with trace eyeblink conditioning, followed by the Morris water maze. Half of aged rats were impaired during trace conditioning. Nearly half of aged animals were also impaired during water maze probe testing. Performance during trace conditioning correlated with performance during water maze testing in aged animals. Further analyses revealed that, as a group, aged animals that were impaired on 1 hippocampal-dependent task were impaired on both tasks. Conversely, aged animals that were unimpaired on 1 task were unimpaired on both tasks. Together, these results suggest that aged-related impairments on 1 hippocampal-dependent task predict age-related impairments on a second hippocampal-dependent procedure. These results have implications for assigning personalized therapeutics to ameliorate age-related cognitive decline. [ABSTRACT FROM AUTHOR]

The hippocampal formation has been associated with a wide variety of functions including spatial navigation and planning, memory encoding and retrieval, relational processing, novelty detection, and imagination. These functions are dissimilar in terms of their behavioral consequences and modality of representation. Consequently, theoretical standpoints have focused on explaining the role of the hip-pocampal formation in terms of either its spatial or nonspatial functions. Contrary to this dichotomy, we propose that it is essential to look beyond these traditional boundaries between mnemonic and spatial functions and focus instead on the processes that these functions have in common. In this framework, we use electrophysiology data from the spatial domain to predict effects on the systems level, both in spatial and nonspatial domains. We initially outline the results of studies that have used findings from spatial navigation in rodents to predict the patterns of brain activity observable in people who are exploring virtual environments. We discuss how certain properties of space-defining neurons enable space to be represented as a mental map of interconnected locations, which are expressed at multiple spatial scales in separate modules in the hippocampal formation. We then suggest that memories are also organized in networks, characterized by mnemonic and temporal hierarchies. We finish by discussing how virtual-reality techniques can be used to create novel lifelike episodes allowing us to look at episodic memory processes while multivariate analysis tools can be used to explore the organizational structure of mnemonic networks. [ABSTRACT FROM AUTHOR]

This study describes a novel spatial memory paradigm for monkeys and reports the effects of neonatal damage to the hippocampus on performance in adulthood. Monkeys were trained to forage in eight boxes hung on the walls of a large enclosure. Each box contained a different food item that varied in its intrinsic reward value, as determined from food preference testing. Monkeys were trained on a spatial and a cued version of the task. In the spatial task, the boxes looked identical and remained fixed in location whereas in the cued task, the boxes were individuated with colored plaques and changed location on each trial. Ten adult Rhesus macaques (5 neonatal sham-operated and 5 with neonatal neurotoxic hippocampal lesions) were allowed to forage once daily until they preferentially visited boxes containing preferred foods. The data suggest that all monkeys learned to discriminate preferred from nonpreferred food locations, but that monkeys with neonatal hippocampal damage committed significantly more working memory errors than controls in both tasks. Furthermore, following selective satiation, controls altered their foraging pattern to avoid the satiated food, whereas lesioned animals did not, suggesting that neonatal hippocampal lesions prohibit learning of specific food-place associations. We conclude that whereas an intact hippocampus is necessary to form specific item-in-place associations, in its absence, cortical areas may support more broad distinctions between food types that allow monkeys to discrim-inate places containing highly preferred foods. [ABSTRACT FROM AUTHOR]

This study investigated the effects of chronic restraint stress and repeated cyclic estradiol pulses on hippocampal CA3 and CA1 dendritic and/or spine morphology and spatial memory in female rats. Sprague-Dawley adult female rats were ovariectomized and then injected over 2 days with 17β-estradiol (10 p.g, s.c.), which was repeated every 4-5 days. While all rats received similar estradiol injection histories, half of the rats were chronically restrained and/or given a final cyclic pulse of estradiol prior to testing on a hippocampal-dependent object placement (OP) task to assess spatial memory. OP testing was performed 2 days after the last restraint session, as well as when the last 2 estradiol pulses best captured the maximal effect on hippocampal CA1 spine density. The data revealed several novel findings: (a) chronic stress or estradiol separately facilitated spatial memory, but did not have the same effects when coadministered, (b) CA1 spine densities negatively correlated with spatial memory, and (c) repeated estradiol pulses failed to prevent stress-induced CA3 dendritic retraction. We also corroborated previous studies showing increased CA1 spine density following estradiol, chronic stress, and behavioral manipulations. The present study uniquely combined chronic stress, repeated estradiol pulses, hippocampal morphology, and behavior within the same animals, allowing for correlational analyses to be performed between CA1 spine morphology and spatial memory. We demonstrate novel findings that chronic stress or estradiol pulses independently facilitate spatial memory, but not when coadministered, and that these effects may involve a balance of CAl apical spine expression that is independent of CA3 dendritic complexity. [ABSTRACT FROM AUTHOR]

Extensive research with laboratory animals indicates that the hippocampus is crucial for the formation and use of spatial memory. Hippocampal lesions in rodents impair spatial memory on radial arm maze tasks. It is unknown whether amnesic patients with hippocampal damage would exhibit similar impairments on a virtual version of a radial arm maze. To evaluate the importance of the hippocampus in spatial learning and memory, we tested amnesic participants with hippocampal damage in a virtual radial arm maze environment. The virtual radial arm maze required participants to learn and remember 4 rewarded arms of 8 total arms. Spatial learning and memory were assessed using the participants' ability to use salient distal cues in the virtual room to remember the 4 rewarded arms. Amnesic participants' latencies were longer and distance traveled was greater to the rewarded arms compared with nonamnesic participants. Amnesic participants made more errors than nonamnesic participants by either entering nonrewarded arms or by revisiting previously entered arms. These data are analogous to previous animal research. Overall, the human hippocampus is necessary for spatial memory and navigation in a virtual radial arm maze task. [ABSTRACT FROM AUTHOR]

The Barnes maze offers advantages for cognitive aging studies, because of its relatively unstressful design and its modest physical demands. The authors therefore undertook a detailed chronological investigation of performance against age, for female Sprague-Dawley and male and female Dark Agouti rats. The trial duration was 10 days. Rats were tested at 6, 11, 14, 17, 20, and 26 months of age, but individual rats were tested at one age only. At 6 months of age, all rats reached the criterion. Sprague-Dawley rats performed best at this age. Impairment began at 14 months in Dark Agouti rats and continued to increase up to 26 months of age. Impairment was greater in Dark Agouti than Sprague- Dawley rats and was greater in females than males. At 26 months, 70% of Sprague-Dawley females reached criterion; of the Dark Agoutis, only 33% of females and 57% of males reached criterion. This study confirms the utility of the Barnes maze as a robust vehicle in aged rats. It also highlights major performance differences between strains and genders in aging rats. [ABSTRACT FROM AUTHOR]

The complexity of an animal's physical environment is known to affect the hippocampus. Captivity may affect hippocampal anatomy and this may be attributable to the limited opportunities for memory-based experiences. This has tangential support, in that differential demands on memory can mediate changes in the hippocampus. What remains unclear is whether captivity directly affects hippocampal architecture and whether providing memory-based experiences in captivity can maintain hippocampal attributes comparable to wild-caught conspecifics. Using food-caching mountain chickadees (Poecile gambeli), we found that wild-caught individuals had larger hippocampal volumes relative to the rest of the telencephalon than captive birds with or without memory-based food-caching experiences, whereas there were no differences in neuron numbers or telencephalon volume. Also, there were no significant differences in relative hippocampal volume or neuron numbers between the captive birds with or without memory-based experiences. Our results demonstrate that captivity reduces hippocampal volume relative to the remainder of the telencephalon, but not at the expense of neuron numbers. Further, memory-based experiences in captivity may not be sufficient to maintain hippocampal volume comparable to wild-caught counterparts. [ABSTRACT FROM AUTHOR]

Recent work from our laboratory demonstrates that both young and adult rats show a preference for directional responding over place navigation in the Morris water task. Based on these findings, previous studies on the postnatal development of spatial learning have most likely assessed the ontogeny of directional responding instead of true place navigation. Here, we examined the development of directional responding and place navigation among young male and female rats using two variants of the Moms water task that specifically require directional and place responses. In the place variant, the hidden platform remained in the same absolute spatial location regardless of pool position. In the direction variant, the platform remained in the same direction in the room regardless of pool position. We found that ability to solve the direction task emerged around 20 to 21 days of age, whereas ability to solve the place task did not emerge until 26 to 27 days of age. These findings indicate that directional responding and place navigation exhibit different developmental trajectories and suggest that the 2 forms of navigation have different neurobiological bases. [ABSTRACT FROM AUTHOR]

Genetically modified mice lacking the glutamate receptor A (GluR-A) subunit of the AMPA receptor (GluR-A-/- mice) display normal spatial reference memory but impaired spatial working memory (SWM). This study tested whether the SWM impairment in these mice could be explained by a greater sensitivity to within-session proactive interference. The SWM performance of GluR-A-/- and wild-type mice was assessed during nonmatching-to-place testing under conditions in which potential proactive interference from previous trials was reduced or eliminated. SWM was impaired in GluR-A-/- mice, both during testing with pseudotrial-unique arm presentations on the radial maze and when conducting each trial on a different 3-arm maze, each in a novel testing room. Experimentally naive GluR-A-/- mice also exhibited chance performance during a single trial of spontaneous alternation. This 1-trial spatial memory deficit was present irrespective of the delay between the sample information and the response choice (0 or 45 min) and the length of the sample phase (0.5 or 5 min). These results imply that the SWM deficit in GluR-A-/- mice is not due to increased susceptibility to proactive interference. [ABSTRACT FROM AUTHOR]

This study uses an operant, behavioral model to assess the daily changes in the decay rate of short-term memory, motivation, and motor ability in rats exposed to chronic restraint. Restraint decreased reward-related motivation by 50% without altering memory decay rate or motor ability. Moreover, chronic restraint impaired hippocampal-dependent spatial memory on the Y maze (4-hr delay) and produced CA3 dendritic retraction without altering hippocampal-independent maze navigation (1-min delay) or locomotion. Thus, mechanisms underlying motivation for food reward differ from those underlying Y maze exploration, and neurobiological substrates of spatial memory, such as the hippocampus, differ from those that underlie short-term memory. Chronic restraint produces functional, neuromorphological, and physiological alterations that parallel symptoms of depression in humans. [ABSTRACT FROM AUTHOR]

V. V. Pravosudov, P. Lavenex, and A. Omanska (2005) reported that undernutrition in the first few weeks' posthatching leads to lower mean hippocampus volumes in adult Western scrub jays (Aphelocoma californica) and to poorer performance on spatial memory tasks. Together with prior work on the effects of poor nutrition on the development of the song system in songbirds, these results fit reasonably well with the view that natural selection determines priorities for investment in the development of neural structures. What seems somewhat anomalous under this view is that undernutrition did not affect the development of color association abilities in scrub jays. This work sets the stage for future comparative research on adaptive priorities in the development of brain and behavior. [ABSTRACT FROM AUTHOR]

Development rates vary among individuals, often as a result of direct competition for food. Survival of young might depend on their learning abilities, but it remains unclear whether learning abilities are affected by nutrition during development. The authors demonstrated that compared with controls, 1-year-old Western scrub jays (Aphelocoma californica) that experienced nutritional deficits during early posthatching development had smaller hippocampi with fewer neurons and performed worse in a cache recovery task and in a spatial version of an associative learning task. In contrast, performance of nutritionally deprived birds was similar to that of controls in 2 color versions of an associative learning task. These findings suggest that nutritional deficits during early development have long-term consequences for hippocampal structure and spatial memory, which, in turn, are likely to have a strong impact on animals' future fitness. [ABSTRACT FROM AUTHOR]

From 5 to 22 months of age, cognitive and emotional responses of nulliparous, primiparous, and multiparous rats were assessed using a dry land maze (DLM) and an elevated plus-maze (EPM) at 4-month intervals. Parous rats exhibited improved spatial memory in the probe and competitive versions of the DLM, and more exploration in the EPM and a novel stimulus test relative to nulliparous females. The nulliparous females, however, outperformed parous rats during the DLM visual cue test at 17 months of age. At 23 months, no differences in stressed corticosterone levels or Golgi-stained hippocampal neurons were observed. Thus, cognitive and emotional modifications were observed in parous rats; the neurobiological mechanisms for these enduring effects, however, remain to be identified. [ABSTRACT FROM AUTHOR]