Changes In Spatial Memory Research Articles

Effect of antidepressants on spatial memory deficit induced by dizocilpine.

Cognitive deficits are a core symptom of schizophrenia. It is controversial whether antidepressants could improve cognitive symptoms in schizophrenia patients. The present study was designed to identify the therapeutic effect of antidepressants on cognitive deficits in schizophrenia. In the present study, adolescent rats were repeatedly exposed to dizocilpine, which can induce cognitive deficits associated with schizophrenia. Then these rats were treated by six antidepressants (fluvoxamine, sertraline, paroxetine, escitalopram, venlafaxine, mirtazapine) or vehicle. The rats in the control group were exposed to vehicle during the study. Lastly, all rats' spatial memory (a major part of cognition) was assessed using the Morris water maze (MWM) test, and the density of hippocampal parvalbumin (PV) interneurons was evaluated to explore possible mechanisms underlying spatial memory change in schizophrenia. The results of the present study supported the hypothesis of a therapeutic effect of fluvoxamine and escitalopram on spatial memory deficit induced by dizocilpine. Additionally, the data of the present study suggested that fluvoxamine and escitalopram remitted hippocampal PV interneuron reduction induced by dizocilpine. The neuroprotective effect of fluvoxamine and escitalopram may partly explain the therapeutic effect of antidepressants on spatial memory deficit in schizophrenia patients.

Protective Actions of Ghrelin on Global Cerebral Ischemia-Induced Memory Deficits

In our study, we investigated transient global cerebral ischemia (TGCI)-induced changes in spatial memory and motor activity together with apoptotic, oxidant, and NO/NOS signaling parameters in rats and the effects of treatment of animals with ghrelin. The TGCI-induced deficiencies of spatial memory and motor activity in the Y-maze and open field tests were attenuated by ghrelin treatment. Furthermore, ghrelin administration lowered the levels of caspase-3 and iNOS elevated by TGCI in the hippocampus. Thus, we conclude that ghrelin exerts a neuroprotective action against hippocampal TGCI injury via influencing apoptotic, oxidant, and/or NO/NOS pathways. If the underlying mechanisms of action of this agent are fully clarified, ghrelin might be a candidate drug for treatment of TGCI-induced memory impairments.

Spatial working memory deficits in male rats following neonatal hypoxic ischemic brain injury can be attenuated by task modifications.

Hypoxia-ischemia (HI; reduction in blood/oxygen supply) is common in infants with serious birth complications, such as prolonged labor and cord prolapse, as well as in infants born prematurely (<37 weeks gestational age; GA). Most often, HI can lead to brain injury in the form of cortical and subcortical damage, as well as later cognitive/behavioral deficits. A common domain of impairment is working memory, which can be associated with heightened incidence of developmental disorders. To further characterize these clinical issues, the current investigation describes data from a rodent model of HI induced on postnatal (P)7, an age comparable to a term (GA 36–38) human. Specifically, we sought to assess working memory using an eight-arm radial water maze paradigm. Study 1 used a modified version of the paradigm, which requires a step-wise change in spatial memory via progressively more difficult tasks, as well as multiple daily trials for extra learning opportunity. Results were surprising and revealed a small HI deficit only for the final and most difficult condition, when a delay before test trial was introduced. Study 2 again used the modified radial arm maze, but presented the most difficult condition from the start, and only one daily test trial. Here, results were expected and revealed a robust and consistent HI deficit across all weeks. Combined results indicate that male HI rats can learn a difficult spatial working memory task if it is presented in a graded multi-trial format, but performance is poor and does not appear to remediate if the task is presented with high initial memory demand. Male HI rats in both studies displayed impulsive characteristics throughout testing evidenced as reduced choice latencies despite more errors. This aspect of behavioral results is consistent with impulsiveness as a core symptom of ADHD—a diagnosis common in children with HI insult. Overall findings suggest that task specific behavioral modifications are crucial to accommodating memory deficits in children suffering from cognitive impairments following neonatal HI.

Training Dependent Changes in Spatial Memory and Zif268 Expression in the Hippocampus and Prefrontal Cortex

Event Abstract Back to Event Training Dependent Changes in Spatial Memory and Zif268 Expression in the Hippocampus and Prefrontal Cortex Francesca R. Farina1* and Sean Commins1 1 Maynooth University, Psychology, Ireland Immediate early genes (IEGs) are strongly implicated in learning‐related plasticity and memory formation (Tischmeyer & Grimm, 1999). Research has demonstrated that activation of IEGs in the hippocampus correlates highly with spatial memory performance (Guzowski et al., 2001). Our aim was to illustrate training dependent changes in spatial memory retention and IEG expression in the hippocampus and prefrontal cortex. Rats were trained to locate a hidden platform in the Morris water maze for five or ten days using two visual, distal cues. Twenty-four hours post-acquisition animals were divided into 4 groups and retested (n = 8/group). Two groups that had been trained for five and ten days, respectively, were tested in the presence of both cues (as per acquisition). The two remaining groups, also having been trained for five and ten days, respectively, were tested with only one cue present. Ninety minutes post‐retention, brains were removed and processed for expression of the well-known IEG Zif268. Behavioural results demonstrated that all animals acquired the task. Further, groups retested in the presence of two cues showed strong retention irrespective of training length. Of the groups tested with one cue, only the group trained for ten days showed good retention. Interestingly, significantly higher Zif268 expression was found in all brain regions for the one cue group compared to the control group after five days. This group difference disappeared after 10 days of training. Findings indicate training‐related behavioural changes which may correspond to a shift in regional IEG expression over time. Acknowledgements This research is funded by the Maynooth University Doctoral Teaching Scholarship. References Guzowski et al. (2001). Experience-Dependent Gene Expression in the Rat Hippocampus after Spatial Learning: A Comparison of the Immediate-Early Genes Arc, c-fos, and zif268. The Journal of Neuroscience, 21(14), 5089–5098. Tischmeyer, W. & Grimm, R. (1999). Activation of immediate early genes and memory formation. Cellular and Molecular Life Sciences, 55, 564–574. Keywords: Hippocampus, prefrontal cortex (PFC), Zif268 expression, spatial memory, water maze Conference: Neuroscience Ireland Young Neuroscientists Symposium 2014 , Dublin, Ireland, 20 Sep - 20 Sep, 2014. Presentation Type: Poster Presentation Topic: Early Career Neuroscience Citation: Farina FR and Commins S (2014). Training Dependent Changes in Spatial Memory and Zif268 Expression in the Hippocampus and Prefrontal Cortex. Front. Neurosci. Conference Abstract: Neuroscience Ireland Young Neuroscientists Symposium 2014 . doi: 10.3389/conf.fnins.2014.87.00033 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 16 Sep 2014; Published Online: 16 Sep 2014. * Correspondence: Ms. Francesca R Farina, Maynooth University, Psychology, Maynooth, Ireland, francesca.farina@gbhi.org Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Francesca R Farina Sean Commins Google Francesca R Farina Sean Commins Google Scholar Francesca R Farina Sean Commins PubMed Francesca R Farina Sean Commins Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

The effects of pregnancy, lactation, and primiparity on object-in-place memory of female rats

Maternal physiology and behavior change dramatically over the course of pregnancy to nurture the fetus and prepare for motherhood. Further, the experience of motherhood itself continues to influence brain functioning well after birth, shaping behavior to promote the survival of offspring. To meet these goals, cognitive abilities, such as spatial memory and navigation, may be enhanced to facilitate foraging behavior. Existing studies on pregnant and maternal rats demonstrate enhanced cognitive function in specific spatial domains. We adopted a novel object-in-place task to assess the ability of female rats to integrate information about specific objects in specific locations, a critical element of foraging behavior. Using a longitudinal design to study changes in spatial memory across pregnancy and motherhood, an advantage in the object-in-place memory of primiparous female rats compared to nulliparous females emerged during lactation not during pregnancy, and was maintained after weaning at 42days postpartum. This enhancement was not dependent on the non-mnemonic variables of anxiety or neophobia. Parity did not affect the type of learning strategy used by females to locate a cued escape platform on a dual-solution water maze task. Results indicate that the enhancement of object-in-place memory, a cognitive function that facilitates foraging, emerged after pregnancy during the postpartum period of lactation and persisted for several weeks after weaning of offspring.

Melatonin attenuates dexamethasone-induced spatial memory impairment and dexamethasone-induced reduction of synaptic protein expressions in the mouse brain

Chronic stress or prolonged exposure to high levels of glucocorticoid induces neuropathological alterations, such as dendritic atrophy of hippocampal or cortical neurons. The chronic administration of high doses of dexamethasone (DEX), a synthetic glucocorticoid receptor agonist, impairs long-term memory and motor coordination, reduces body weight and induces mortality in mice. DEX is typically administered clinically for a prolonged period. Therefore, we are interested in studying the mechanism by which chronic DEX administration affects cognitive function. In this study, we attempted to explore whether chronic DEX administration alters the process of memory formation and to determine the mechanism underlying the detrimental effect of DEX. The results showed that mice treated with DEX for 21 consecutive days had significantly impaired spatial memory in the Morris Water Maze task. Mice treated with DEX had prolonged water maze performance latencies and spent less time in the target quadrant compared to the control group. Furthermore, DEX reduced brain-derived neurotrophic factor (BDNF), N-methyl-d-aspartate (NMDA) receptor subunit (NR2A/B), calcium/calmodulin-dependent protein kinase II (CaMKII) in both the prefrontal cortex and hippocampus and synaptophysin in the prefrontal cortex. We also investigated whether melatonin, a hormone synthesized in the pineal gland, could protect against DEX-induced changes in spatial memory and synaptic plasticity. The results showed that mice pretreated with melatonin prior to the DEX treatment had shorter escape latencies and remained in the target quadrant longer compared to the group only treated with DEX. Melatonin significantly prevented a DEX-induced reduction in the expression of NR2A/B, BDNF, CaMKII and synaptophysin. The results from the present study demonstrate that melatonin pretreatment prevents cognitive impairment caused by DEX. However, the precise mechanism by which melatonin affects cognitive function requires further investigation.

Distinct roles of methamphetamine in modulating spatial memory consolidation, retrieval, reconsolidation and the accompanying changes of ERK and CREB activation in hippocampus and prefrontal cortex

Drugs of abuse modulated learning and memory in humans yet the underlying mechanism remained unclear. The extracellular signal-regulated kinase (ERK) and the transcription factor cAMP response element-binding protein (CREB) were involved in neuroplastic changes associated with learning and memory. In the current study, we used a Morris water maze to examine the effect of methamphetamine (METH) on different processes of spatial memory in mice. We then investigated the status of ERK and CREB in the hippocampus and prefrontal cortex (PFC). We found that 1.0 mg/kg dose of METH facilitated spatial memory consolidation when it was injected immediately after the last learning trial. In contrast, the same dose of METH had no effect on spatial memory retrieval when it was injected 30 min before the test. Furthermore, 1.0 mg/kg dose of METH injected immediately after retrieval had no effect on spatial memory reconsolidation. Activation of both ERK and CREB in the hippocampus was found following memory consolidation but not after retrieval or reconsolidation in METH-treated mouse groups. In contrast, activation of both ERK and CREB in the PFC was found following memory retrieval but not other processes in METH-treated mouse groups. These results suggested that METH facilitated spatial memory consolidation but not retrieval or reconsolidation. Moreover, activation of the ERK and CREB signaling pathway in the hippocampus might be involved in METH-induced spatial memory changes.

Changes in spatial memory and BDNF expression to simultaneous dietary restriction and forced exercise

Previous literature suggests that learning and memory formation can be influenced by diet and exercise. In the current study, we investigated the combined effects of forced swimming exercise (FSE) and every other day fasting (EODF) on spatial memory formation and on the levels of brain-derived neurotrophic factor (BDNF) in the hippocampus of Wistar male rats. The radial arm water maze (RAWM) paradigm was used to assess changes in learning and memory formation, whereas ELISA assay was used to measure BDNF protein levels. The FSE and/or EODF were simultaneously instituted for 6 weeks. Results show that FSE improved learning, short-term as well as long-term memory formation, and significantly increased BDNF protein in the hippocampus (p<0.05). However, EODF had no effect on either spatial learning and memory formation or the levels of hippocamapal BDNF protein (p>0.05). In addition, EODF did not modulate beneficial effect of swimming exercise on cognitive function (p>0.05). Thus exercise enhanced, while EODF did not affect spatial learning and memory formation.

Antidepressant suppression of REM and spindle sleep impairs hippocampus-dependent learning and memory but fosters striatal-dependent strategies

AbstractREM sleep enhances hippocampus-dependent associative memory but has little impact on striatal-dependent procedural learning. Antidepressant medications like desipramine (DMI) inhibit rapid-eye-movement (REM) sleep but it is little understood how antidepressant treatments affect learning. We found that DMI strongly suppressed REM sleep in rats for several hours and impaired reconsolidation of a familiar maze and consolidation of moved baited positions (reversal learning) in a sleep-dependent fashion. Unexpectedly, DMI also reduced the spindle-rich transition-to-REM sleep state (TR) and spatial memory changes were more related to TR than to REM sleep. Working memory was unaffected, but overnight reference memory was significantly impaired and subjects increased reliance on non-hippocampal strategies. Procedural memory performance was positively correlated with increases in non-REM sleep after DMI serving to offset memory declines, partially preserving performance. Our results suggest that familiar memories are re-consolidated during REM sleep, reversal memories consolidated during TR, and procedural memories consolidated during non-REM sleep.

Prophylactic lithium alleviates postoperative cognition impairment by phosphorylating hippocampal glycogen synthase kinase-3β (Ser9) in aged rats

Postoperative cognition impairment is a perishing complication in elderly patients undergone surgeries. Lithium is widely used in psychiatric patients for its role in neuronal protection, whereas whether or not it could attenuate surgery-associated postoperative cognition dysfunction used prophylactically is not well defined. After approval by the Institutional Animal Care and Use Committee, 48 male Sprague–Dawley rats aged 18 months old were randomly divided into three groups with 16 each: i, no surgeries and drugs were given; ii, surgical procedures were performed only without drug delivery; iii, prophylactic 2 mM/kg lithium chloride was given intraperitoneally once a day for seven days before surgeries. The change in spatial memory was assessed with Morris Water Maze (MWM), and the activation of PI3K/AKT/mTOR pathway was detected, and the levels of hippocampal glycogen synthase kinase-3β (p-GSK-3β) phosphorylation at serine 9 and interleukin-1β (IL-1β) were measured. The MWM detection showed that both swimming latency and distance were considerably prolonged by the surgeries, but these changes could be markedly shortened by prophylactic lithium administration. Meanwhile, the changes in the hippocampal PI3K cascades and p-GSK-3β and IL-1β expression displayed corresponding changes that were parallel to the alterations of spatial memory, and inhibition of PI3K and GSK-3β suggested upstream PI3K activation leads to downstream change in p-GSK-3β and IL-1β. These results indicate, at least in part, that prophylactic lithium can alleviate surgery-associated impairment of the spatial memory in aged rats which is strongly associated with the reduced levels of hippocampal p-GSK-3β and IL-1β resulted from the activation of PI3K/AKT/mTORC2 pathway.

Long-Term Effects of 56Fe Irradiation on Spatial Memory of Mice: Role of Sex and Apolipoprotein E Isoform

To assess whether the effects of cranial (56)Fe irradiation on the spatial memory of mice in the water maze are sex and apolipoprotein E (apoE) isoform dependent and whether radiation-induced changes in spatial memory are associated with changes in the dendritic marker microtubule-associated protein 2 (MAP-2) and the presynaptic marker synaptophysin. Two-month-old male and female mice expressing human apoE3 or apoE4 received either a 3-Gy dose of cranial (56)Fe irradiation (600 MeV/amu) or sham irradiation. Mice were tested in a water maze task 13 months later to assess effects of irradiation on spatial memory retention. After behavioral testing, the brain tissues of these mice were analyzed for synaptophysin and MAP-2 immunoreactivity. After irradiation, spatial memory retention of apoE3 female, but not male, mice was impaired. A general genotype deficit in spatial memory was observed in sham-irradiated apoE4 mice. Strikingly, irradiation prevented this genotype deficit in apoE4 male mice. A similar but nonsignificant trend was observed in apoE4 female mice. Although there was no change in MAP-2 immunoreactivity after irradiation, synaptophysin immunoreactivity was increased in irradiated female mice, independent of genotype. The effects of (56)Fe irradiation on the spatial memory retention of mice are critically influenced by sex, and the direction of these effects is influenced by apoE isoform. Although in female mice synaptophysin immunoreactivity provides a sensitive marker for effects of irradiation, it cannot explain the apoE genotype-dependent effects of irradiation on the spatial memory retention of the mice.

Spatial Memory Using Active Allothetic Place Avoidance in Adult Rats After Isoflurane Anesthesia

We described a paradigm of active allothetic place avoidance (AAPA) as a measure of spatial memory in adult rats. We hypothesized that, pending successful AAPA training, treatment with isoflurane would trigger spatial memory deficits. Fifteen of 20 adult rats were successfully trained and randomly allocated to control and isoflurane treatment groups. An additional 7 animals were used to demonstrate hemodynamic stability during general anesthesia. After training, experimental animals received a 2-hour isoflurane anesthetic. General endotracheal anesthesia was maintained at an isoflurane concentration of 1.8% to 2%. After intervention, retention of training was tested on postanesthesia days 1, 3, and 7. Animals treated with isoflurane displayed selected spatial memory changes up to postanesthesia day 7. There were 2 findings of decreased active avoidance behavior in rats receiving isoflurane: a significant (P=0.029) reduction in maximum path of avoidance in the isoflurane-treated rats compared with controls, and a significant (P=0.038) increase in total path length in the controls. No other measured AAPA parameters achieved statistical significance. Control animals demonstrated increased active avoidance behavior in the AAPA task compared with isoflurane-treated animals. Animals exposed to 2-hour isoflurane general anesthetic had a reduction in the maximum path of avoidance measure up to 7 days postanesthesia, whereas gross spatial parameters such as number of entrances into the shock zone were not significantly different between groups. The AAPA model may prove useful in ascertaining the learning and memory deficits of postoperative cognitive dysfunction.

Nasal Administration of Quercetin Liposomes Improves Memory Impairment and Neurodegeneration in Animal Model of Alzheimer's Disease

Problem statement: At present, the development of protective strategy against Alzheimer’s Disease (AD) is increasing its importance due to the high prevalence of AD, a limitation of therapeutic efficacy and its high impacts on economic and social aspects. The development of the preventive and therapeutic strategy to protect against the path physiology induced by free radicals in AD from antioxidant has gained very much concentration. Quercetin, one of the flavonoids in fruits and vegetables, has a powerful antioxidant activity both in vitro and in vivo. However, poor absorption, rapid metabolism and limited ability to cross the blood-brain-barrier are obstacles to its use for treatment of AD. Liposome’s have been used as an effective delivery system to the brain. Advantages associated with the nasal administration over oral route include higher bioavailability due to no first pass hepatic metabolism and rapid absorption leading to shorter time to onset of effect. Based on all these points, the possible effects of quercetin liposomes via nasal route on improving cognitive behavior and neurodegeneration in animal model of Alzheimer’s disease were investigated. Approach: Male Wistar rats were pretreated with quercetin liposome’s, containing 0.5 mg of quercetin in 20 μL (dose = 20 μg), via intranasal route once daily continually for 2 weeks before and 1 week after AF64A administration. Learning and memory was evaluated using the Morris water maze test at 7 days after the AF64A administration and then the rats were sacrificed for determining the density of neurons and cholinergic neurons in hippocampus using histological and immunohistochemical techniques. Results: Nasal administration of quercetin liposome’s significantly prevented changes of spatial memory of AF64A treated rats. The cognitive enhancement of quercetin liposome’s was found to be related to its ability to inhibit the degeneration of neurons and cholinergic neurons in hippocampus. Conclusion: Nasal administration of quercetin liposome’s possessed cognitive enhancer and neuroprotectant in animal model of AD, suggesting a potential novel therapeutic strategy against AD of quercetin liposomes.

Changes in spatial memory and BDNF expression to concurrent dietary restriction and voluntary exercise

Substantial data suggest that cognitive function can be influenced by many lifestyle activities associated with changes in energy metabolism such as exercise and diet. In the current study, we investigated the combined effects of voluntary exercise (access to running wheels) and dietary restriction (every other day fasting, EODF) on spatial memory formation and on the levels of brain-derived neurotrophic factor (BDNF) in the hippocampus of Wistar male rats. Spatial learning and memory formation was assessed using the radial arm water maze (RAWM) paradigm, while BDNF protein was measured using ELISA test. Voluntary exercise and/or EODF were instituted for 6 weeks. Voluntary exercise alone significantly enhanced short-term, intermediate-term, and long-term memory formation, and increased BDNF protein levels in the hippocampus. EODF enhanced mean running wheel activity by approximately twofold. However, EODF did not modulate the effects of exercise on memory formation and expression of BDNF. In addition, EODF alone had no effect on memory and BDNF protein in the hippocampus. In conclusion, results of this study indicate that exercise enhanced while EODF had neutral effect on both spatial memory formation and hippocampus BDNF levels.

Spatial memory and hippocampal plasticity are differentially sensitive to the availability of choline in adulthood as a function of choline supply in utero

Altered dietary choline availability early in life leads to persistent changes in spatial memory and hippocampal plasticity in adulthood. Developmental programming by early choline nutrition may determine the range of adult choline intake that is optimal for the types of neural plasticity involved in cognitive function. To test this, male Sprague–Dawley rats were exposed to a choline chloride deficient (DEF), sufficient (CON), or supplemented (SUP) diet during embryonic days 12–17 and then returned to a control diet (1.1 g choline chloride/kg). At 70 days of age, we found that DEF and SUP rats required fewer choices to locate 8 baited arms of a 12-arm radial maze than CON rats. When switched to a choline-deficient diet (0 g/kg), SUP rats showed impaired performance while CON and DEF rats were unaffected. In contrast, when switched to a choline-supplemented diet (5.0 g/kg), DEF rats' performance was significantly impaired while CON and SUP rats were less affected. These changes in performance were reversible when the rats were switched back to a control diet. In a second experiment, DEF, CON, and SUP rats were either maintained on a control diet, or the choline-supplemented diet. After 12 weeks, DEF rats were significantly impaired by choline supplementation on a matching-to-place water-maze task, which was also accompanied by a decrease in dentate cell proliferation in DEF rats only. IGF-1 levels were elevated by both prenatal and adult choline supplementation. Taken together, these findings suggest that the in utero availability of an essential nutrient, choline, causes differential behavioral and neuroplastic sensitivity to the adult choline supply.

How do biases in spatial memory change as children and adults are learning locations?

This investigation tracked changes in categorical bias (i.e., placing objects belonging to the same spatial group closer together than they really are) while 7-, 9-, and 11-year-olds and adults were learning a set of locations. Participants learned the locations of 20 objects marked by dots on the floor of an open square box divided into quadrants. At test, participants attempted to place the objects in the correct locations without the dots and boundaries. In Experiment 1, we probed categorical bias during learning by alternating learning and test trials. Categorical bias was high during the first test trial and decreased over the second and third test trials. In Experiment 2, we manipulated opportunities for learning by providing participants with either one, two, three, or four learning trials prior to test. Participants who experienced one or two learning trials exhibited more bias at test than did those who experienced four learning trials. The discussion focuses on how categorical bias emerges through interactions between the cognitive system and task structure.

Characterization of verbal and spatial memory changes from moderate to supraphysiological increases in serum testosterone in healthy older men

It has been suggested that cognitive changes in response to T supplementation may occur within an ideal range. The objective of this study was to compare the cognitive responses of older, eugonadal men in whom moderate or large increases in serum testosterone levels was induced by exogenous testosterone supplementation. Randomized, double-blind, placebo-controlled study with subsequent grouping of participants according to average increase in circulating T from baseline. Community dwelling participants. Fifty-seven healthy, eugonadal, community dwelling male volunteers, mean age 67 years (+/-11 years). Participants were randomized to receive weekly intramuscular (i.m.) injections of either 50, 100 or 300 mg T enanthate or placebo (saline) injection for 6 weeks. Cognitive evaluations using a battery of neuropsychological tests were conducted at baseline, weeks 3 and 6 of treatment and after 6 weeks of wash-out. Performance on cognitive tests of verbal and spatial memory. Men with moderate increases in serum T and/or its metabolites demonstrated significant improvements in verbal and spatial memory. In contrast, men with large or low increases in circulating T levels, failed to demonstrate significant changes in memory. These results suggest that in healthy older men, beneficial changes in cognitive function induced by T supplementation are most evident with moderate changes in cognition from moderate to high T supplementation increases in T levels. Large or no to low increases in T levels do not appear to appreciably effect cognition.

Stress‐Induced Changes in Spatial Memory are Sexually Differentiated and Vary Across the Lifespan

Stress exposure, depending on intensity and duration, elicits adaptive or maladaptive physiological changes. The same general pattern of advantageous versus deleterious stress effects appears to exist for some cognitive functions, particularly spatial learning and memory performance. This article reviews sex differences in response to stress on a variety of spatial tasks. In general, females are more resistant than males to stress-induced impairments on spatial tasks, including the radial arm maze and object placement. In young adulthood, chronic stress (restraint, 6 h per day for 21 days) impairs male performance on both tasks but leads to behavioural enhancements in females. Furthermore, these sex-dependent stress effects are influenced by both organisational and activational oestrogenic effects. Additionally, sex-specific stress responses vary depending on developmental age at the time of stress exposure. Male behavioural stress responses appear fixed across the lifespan (i.e. stress-induced cognitive impairments) whereas female stress responses appear more variable (i.e. stress-induced enhancements observed in young adulthood are different in response to prenatal stress and diminished following stress exposure at old age). These findings underscore the point that many effects obtained in males cannot be generalised to females and highlight the need to investigate the stress response at different ages and in both sexes.

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.

Chronic treatment of old rats with donepezil or galantamine: effects on memory, hippocampal plasticity and nicotinic receptors

The function of the cholinergic system is known to change during normal aging and in pathological conditions such as Alzheimer’s disease. The present study was designed to assess, within the same group of old animals, the behavioral, electrophysiological and neurochemical effects of chronic treatment with agents that increase the function of the cholinergic system through both muscarinic and nicotinic mechanisms. Doses were determined that produced 60% cholinesterase inhibition by donepezil and galantamine for the old rats. This was chosen to be analogous to therapeutic levels achieved for treatment of human Alzheimer’s disease patients with these agents. Because of the well-known age-related changes in spatial memory and hippocampal synaptic plasticity, spatial working memory in the radial eight-arm maze and hippocampal long-term potentiation induction and decay, as well as nicotinic receptor density and affinity, were measured in old rats implanted with minipumps that delivered donepezil, galantamine or saline. There was no effect of drug treatment on baseline synaptic transmission or on the threshold or magnitude of long-term potentiation induction. Both drug treatment groups, however, showed significantly extended long-term potentiation decay times at the perforant path–granule cell synapse over the saline control animals, as measured during the week following induction. Both drugs also elevated the number of nicotinic receptors within the hippocampus and neocortex. This is the first demonstration of cholinergic modulation of synaptic plasticity over the time-course of days. Furthermore, the durability of long-term potentiation was significantly, positively correlated with nicotinic receptor binding in the hippocampus. Chronic treatment with donepezil or galantamine had no significant effect on a well-learned spatial working memory task on the radial maze. These data suggest that the therapeutic doses of cholinesterase inhibitors used to treat patients with Alzheimer’s disease may have effects on neurophysiology and neurochemistry that are close to the threshold for producing detectable behavioral improvements.