Lisa K. Marriott

Patterns of brain acetylcholine release predict individual differences in preferred learning strategies in rats

Acetylcholine release was measured simultaneously in the hippocampus and dorsal striatum of rats before and during training on a maze that could be learned using either a hippocampus-dependent spatial strategy or a dorsal striatum-dependent turning strategy. A probe trial administered after rats reached a criterion of 9/10 correct responses revealed that about half of the rats used a spatial strategy and half a turning strategy to solve the task. Acetylcholine release in the hippocampus, as well as the ratio of acetylcholine release in the hippocampus vs. the dorsal striatum, measured either before or during training, predicted these individual differences in strategy selection during learning. These findings suggest that differences in release of acetylcholine across brain areas may provide a neurobiological marker of individual differences in selection of the strategies rats use to solve a learning task.

Multiple pathways transmit neuroprotective effects of gonadal steroids

Numerous preclinical studies suggest that gonadal steroids, particularly estrogen, may be neuroprotective against insult or disease progression. This paper reviews the mechanisms contributing to estrogen-mediated neuroprotection. Rapid signaling pathways, such as MAPK, P13K, Akt, and PKC, are required for estrogens ability to provide neuroprotection. These rapid signaling pathways converge on genomic pathways to modulate transcription of E2-responsive genes via ERE-dependent and ERE-independent mechanisms. It is clear that both rapid signaling and transcription are important for estrogens neuroprotective effects. A mechanistic understanding of estrogen-mediated neuroprotection is crucial for the development of therapeutic interventions that enhance quality of life withou deleterious side effects.

Cooperation between memory systems: acetylcholine release in the amygdala correlates positively with performance on a hippocampus-dependent task.

The present experiment examined the relationship between release of acetylcholine (ACh) in the amygdala and performance on a hippocampus-dependent spatial working memory task. Using in vivo microdialysis, the authors measured ACh release in rats during testing on a spontaneous alternation task. Amygdala ACh release was positively correlated with performance on the hippocampus-dependent task. These findings suggest that activation of the amygdala promotes processing in other neural systems important for learning and memory.

Short-term estrogen treatment in ovariectomized rats augments hippocampal acetylcholine release during place learning

Estrogen modulates learning and memory in ovariectomized and naturally cycling female rats, especially in tasks using spatial learning and navigation. Estrogen also modulates cholinergic function in various forebrain structures. Past studies have shown positive correlations between hippocampal ACh output and performance on hippocampus-dependent tasks. The present study examined whether estradiol replacement would potentiate hippocampal ACh release during place learning. In vivo microdialysis and HPLC were used to measure extracellular ACh levels in the hippocampus of ovariectomized female rats that had received s.c. injections of 17beta-estradiol (10 microg) or sesame oil (vehicle treatment) 48 and 24h prior to training on a place task. Estrogen did not alter baseline levels of extracellular ACh in the hippocampus. During training, hippocampal ACh increased in ovariectomized rats regardless of estrogen status. However, while estradiol did not enhance learning in this experiment, estradiol significantly potentiated the increase in hippocampal ACh release seen during place training. This represents the first demonstration of on-line assessment of ACh output in hippocampus during learning in female rats and suggests that estrogen-dependent modulation of ACh release during training might control activation of different neural systems used during learning.

Learning and memory performance in mice lacking the GAL‐R1 subtype of galanin receptor

The neuropeptide galanin induces performance deficits in a wide range of cognitive tasks in rodents. Three G‐protein‐coupled galanin receptor subtypes, designated GAL‐R1, GAL‐R2 and GAL‐R3, have been cloned. The present study examined the role of GAL‐R1 in cognition by testing mice with a null mutation in Galr1 on several different types of learning and memory tasks. Assessments of general health, neurological reflexes, sensory abilities and motor functions were conducted as control measures. Mutant mice were unimpaired in social transmission of food preference and the Morris water maze. In tests of fear conditioning, mutant mice were unimpaired in a delay version of cued fear conditioning. However, mice homozygous for the null mutation were impaired in a trace version of cued fear conditioning. Mutant mice were unimpaired in contextual fear conditioning, whether training was by the delay or trace protocol. General health, neurological reflexes, sensory abilities and motor functions did not differ across genotypes, indicating that the trace fear conditioning deficit was not an artifact of procedural disabilities. The findings of normal performance on several cognitive tasks and a selective deficit in trace cued fear conditioning in homozygous GAL‐R1 mutant mice are discussed in terms of hypothesized roles of the GAL‐R1 subtype. The generally normal phenotype of GAL‐R1 null mutants supports the use of this line for identification of the receptor subtypes that mediate the cognitive deficits produced by exogenous galanin.

Long-term estrogen therapy worsens the behavioral and neuropathological consequences of chronic brain inflammation.

Alzheimers disease (AD) is accompanied by chronic neuroinflammation and occurs with greater incidence in postmenopausal women. The increased incidence may be delayed by estrogen replacement therapy (ERT). The authors investigated the interaction of chronic ERT and lipopolysaccharide (LPS)-induced neuroinflammation in the female rat. Ovariectomy did not impair water maze performance; however, addition of chronic ERT or neuroinflammation resulted in an impairment that became exacerbated by the simultaneous occurrence of both conditions. Chronic LPS activated microglia, which was not reduced by ERT. Intact females receiving LPS infusion were not impaired in the water maze and had significantly fewer activated microglia. Results suggest that chronic ERT in postmenopausal women may exacerbate the memory impairment induced by the chronic neuroinflammation associated with AD.

Galanin peptide levels in hippocampus and cortex of galanin-overexpressing transgenic mice evaluated for cognitive performance.

Galanin-overexpressing transgenic mice (GAL-tg) generated on a dopamine beta-hydroxylase promoter were previously shown to express high levels of galanin mRNA in the locus coeruleus, and to perform poorly on challenging cognitive tasks. The present study employed radioimmunoassay to quantitate the level of galanin peptide overexpression in two brain regions relevant to learning and memory, the hippocampus and cerebral cortex. Approximately 4-fold higher levels of galanin were detected in the hippocampus of GAL-tg as compared to WT. Approximately 10-fold higher levels of galanin were detected in the frontal cortex of GAL-tg as compared to WT. A second cohort of GAL-tg and WT again showed high levels of galanin overexpression in GAL-tg as compared to WT in both brain regions. Correlation analyses were conducted between galanin peptide concentrations and behavioral scores on four learning and memory tasks: the Morris water maze, social transmission of food preference, standard delay fear conditioning, and trace fear conditioning. While some significant correlations were detected, neither hippocampal nor cortical galanin levels in the two cohorts of GAL-tg consistently correlated with performance across these diverse cognitive tasks. Several interpretations of these findings are discussed, including the possibility that a threshold level of galanin overexpression is sufficient to impair performance on learning and memory tasks in mice.

Using Health Information Technology to Engage Communities in Health, Education, and Research

The Internet can be used for personal health management as well as to facilitate partnerships and data-sharing in a community setting. Engaging Communities In August 2011, scientists and policy-makers held a conference entitled “Using Information Technology to Improve Community Health: How Health Care Reform Supports Innovation.” At the conference, four “Think Tank” sessions convened, one which was “Health Information Technology (HIT) as a Resource to Improve Community Health and Education.” During this session, a diverse group of 30 individuals discussed ways that HIT could engage communities to improve patient health, education, and research involvement. The August 2011 Clinical and Translational Science Awards conference “Using IT to Improve Community Health: How Health Care Reform Supports Innovation” convened four “Think Tank” sessions. Thirty individuals, representing various perspectives on community engagement, attended the “Health information technology (HIT) as a resource to improve community health and education” session, which focused on using HIT to improve patient health, education, and research involvement. Participants discussed a range of topics using a semistructured format. This article describes themes and lessons that emerged from that session, with a particular focus on using HIT to engage communities to improve health and reduce health disparities in populations.

Let's Get Healthy! Health awareness through public participation in an education and research exhibit.

Background: Health information technology (HIT) offers a resource for public empowerment through tailored information.Objective: Use interactive community health events to improve awareness of chronic disease risk factors while collecting data to improve health.Methods:Lets Get Healthy! is an education and research program in which participants visit interactive research stations to learn about their own health (diet, body composition, blood chemistry). HIT enables computerized data collection that presents participants with immediate results and tailored educational feedback. An anonymous wristband number links collected data in a population database.Results and Lessons Learned: Communities tailor events to meet community health needs with volunteers trained to conduct research. Participants experience being a research participant and contribute to an anonymous population database for both traditional research purposes and open-source community use.Conclusions: By integrating HIT with community involvement, health fairs become an interactive method for engaging communities in research and raising health awareness.

Estrogen replacement regimen and brain infusion of lipopolysaccharide differentially alter steroid receptor expression in the uterus and hypothalamus

The regimen of estrogen replacement can alter the consequences of estrogen therapy and stressors. To determine the long-term effects and interaction of these systems on the brain and periphery, adult female rats were infused with lipopolysaccharide (LPS) into the fourth ventricle of the brain for 4 weeks, and ovariectomized rats were administered either constant or pulsed regimens of estrogen replacement (17β-estradiol) until sacrifice at 8 weeks. Constant, but not pulsed, estrogen replacement reduced ERα and increased HSP90, HSP70, and PRB uterine protein levels. Both estrogen regimens increased ERβ, HSP27, and PRA uterine proteins. Both regimens reduced hypothalamic levels of ERα, but not ERβ, HSP, or PR. No changes were observed in the hippocampus. Long-term brain infusion of LPS activated microglia and reduced body weight, but did not alter corticosterone or nitrotyrosine levels. LPS infusion into intact rats suppressed uterine weight, increased ERα and decreased HSP90 in the uterus. LPS did not alter uterine weight in ovariectomized rats treated with constant or pulsed estrogen. Together, these data suggest the timing of estrogen replacement and neuroinflammatory stressors can profoundly affect uterine and hypothalamic steroid receptor expression and may be important parameters to consider in the post-menopausal intervention with estrogen.