A5065272435- Stress Responses and Cortisol
- Neuroendocrine regulation and behavior
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Tryptophan and brain disorders
- Neurotransmitter Receptor Influence on Behavior
- Memory and Neural Mechanisms
- Hormonal Regulation and Hypertension
- Genetic Associations and Epidemiology
- Adipose Tissue and Metabolism
- Genetic Mapping and Diversity in Plants and Animals
- Bioinformatics and Genomic Networks
- Epigenetics and DNA Methylation
- Neurogenesis and neuroplasticity mechanisms
- Genetics and Neurodevelopmental Disorders
- Circadian rhythm and melatonin
- Spatial Cognition and Navigation
- Gene expression and cancer classification
- Connective Tissue Growth Factor Research
- Genetic and phenotypic traits in livestock
- Machine Learning in Bioinformatics
- Birth, Development, and Health
- Drug Transport and Resistance Mechanisms
- Wnt/β-catenin signaling in development and cancer
University of Michigan
2011-2025
Neuroscience Institute
2007
Activation of the hypothalamic-pituitary-adrenal (HPA) axis occurs in response to organism's innate need for homeostasis. The glucocorticoids (GCs) that are released into circulation upon acute activation HPA perform stress-adapti
Common genetic factors likely contribute to multiple psychiatric diseases including mood and substance use disorders. Certain stable, heritable traits reflecting temperament, termed externalizing or internalizing, play a large role in modulating vulnerability these To model tendencies, we selectively bred rats for high low exploration novel environment [bred High Responders (bHR) vs. Low (bLR)]. identify genes underlying the response selection, phenotyped genotyped 538 from an F2 cross...
Stress is a major influence on mental health status; the ways that individuals respond to or copes with stressors determine whether they are negatively affected in future. responses established by an interplay between genetics, environment, and life experiences. Psychosocial stress particularly impactful during adolescence, critical period for development of mood disorders. In this study we compared two established, selectively-bred Sprague Dawley rat lines, "internalizing" bred Low...
Externalizing and internalizing behavioral tendencies underlie many psychiatric substance use disorders. These are associated with differences in temperament that emerge early development via the interplay of genetic environmental factors. To better understand neurobiology temperament, we have selectively bred rats for generations to produce two lines highly divergent behavior: Low Responders (bLRs) inhibited anxious novel environments, whereas High (bHRs) exploratory, sensation-seeking,...
Repeated stress enhances vulnerability to neural dysfunction that is cumulative over the course of lifespan. This contributes cognitive deficits observed during aging. In addition, aging associated with dysregulation limbic–hypothalamic–pituitary–adrenal (LHPA) axis, leading a delayed termination response. delay, in turn, increases exposure glucocorticoids and exacerbates likelihood damage. Here we asked whether similar effects could emerge at an early age as result genetic variations level...
Abstract Microglia play critical roles in healthy brain development and function, as well the neuropathology underlying a range of diseases. Despite evidence for role microglia affective regulation mood disorders, little is known regarding how variation status relates to individual differences emotionality. Using selective breeding model, we have generated rat lines with unique temperamental phenotypes that reflect broad emotional traits: bred low responder rats (bLRs) are novelty-averse...
Transcriptional profiling has become a common tool for investigating the nervous system. During analysis, differential expression results are often compared to functional ontology databases, which contain curated gene sets representing well-studied pathways. This dependence can cause neuroscience studies be interpreted in terms of pathways documented better studied tissues (
Abstract Stress is a major influence on mental health status; the ways that individuals respond to or copes with stressors determine whether they are negatively affected in future. responses established by an interplay between genetics, environment, and life experiences. Psychosocial stress particularly impactful during adolescence, critical period for development of mood disorders. In this study we compared two established, selectively-bred Sprague Dawley rat lines, “internalizing” bred Low...
Abstract The ability to respond unexpected or novel stimuli is critical for survival. Determining that a stimulus indeed requires memory ascertain its lack of familiarity. As the long‐term synaptic changes involved in formation require cAMP response element binding protein (CREB), we examined extent which CREB responses environments. These environments typically trigger an endocrine stress response. Thus, measured behavioural and hormone three one familiar environment mice with targeted...
Adolescent drug use reliably predicts increased addiction liability in adulthood, but not all individuals are equally impacted. To explore the biological bases of this differential reactivity to early life experience, we used a genetic rat model temperament and evaluated impact adolescent cocaine exposure on adult psychomotor sensitization. Relative bred low-responder (bLR) rats, high-responders (bHR) more sensitive psychomotor-activating effects reinstate drug-seeking behavior readily...
The impact of a previously successful or unsuccessful experience on the subsequent acquisition related task is not well understood. nature past may have even greater in individuals with learning deficits, as their cognitive processes can be easily disrupted. Mice targeted disruption α and δ isoforms cAMP-response element-binding protein (CREB) gene (CREB αδ- -deficient mice) genetic vulnerability to impaired memory that highly influenced by experimental conditions. Thus, we studied prior...
Abstract Selectively-bred High Responder (bHR) and Low (bLR) rats model the extreme externalizing internalizing behavior accompanying many psychiatric disorders. To elucidate gene expression underlying these heritable behavioral differences, bHRs bLRs (generation 37) were used to produce a F 0 -F 1 2 cross. We measured exploratory locomotion, anxiety-like behavior, reward cue sensitivity (Pavlovian Conditioned Approach), performed hippocampal RNA-Seq in male female s (n=24) (n=250)....
Abstract Background For over 16 years, we have selectively bred rats to show either high or low levels of exploratory activity within a novel environment. These “bred High Responder” (bHR) and Low (bLR) serve as model for temperamental extremes, exhibiting large differences in many internalizing externalizing behaviors relevant mood substance abuse disorders. Methods Our study elucidated persistent gene expression related bHR/bLR phenotype across development adulthood the hippocampus, region...
Abstract Common genetic factors likely contribute to multiple psychiatric diseases including mood and substance use disorders. Certain stable, heritable traits reflecting temperament, termed externalizing or internalizing, play a large role in modulating vulnerability these To model tendencies, we selectively bred rats for high low exploration novel environment (bred High Responders (bHR) vs. Low (bLR)). identify genes underlying the response selection, phenotyped genotyped 558 from an F 2...
Abstract Transcript labelling in intact tissues using situ hybridization chain reaction has potential to provide vital spatiotemporal information for molecular characterization of heterogeneous neuronal populations. However, it remains relatively unexplored fresh-frozen brain which provides more flexible utilization than perfused tissue. In the present study, we optimized combination rodent brains and then evaluated uniformity between two clearing methods, CLARITY iDISCO + . We found that...