Alcohol and fear conditioning produce strain-specific changes in the dorsal hippocampal transcriptome of adolescent C57BL/6J and DBA/2J mice.

Background: Adolescent sensitivity to alcohol is influenced by genetic background. Data from our laboratory suggested that adolescent C57BL/6J and DBA/2J inbred mice differed in susceptibility to alcohol-induced deficits in dorsal hippocampus-dependent contextual fear learning.

Methods: To investigate the biological underpinnings of this strain difference, we examined dorsal hippocampus gene expression using RNA-sequencing after alcohol or saline administration followed by Pavlovian fear conditioning across male and female C57BL/6J and DBA/2J adolescents.

Alcohol and stress exposure across the lifespan are key risk factors for Alzheimer's Disease and cognitive decline.

Alzheimer's Disease and related dementias (ADRD) are an increasing threat to global health initiatives. Efforts to prevent the development of ADRD require understanding behaviors that increase and decrease risk of neurodegeneration and cognitive decline, in addition to uncovering the underlying biological mechanisms behind these effects. Stress exposure and alcohol consumption have both been associated with increased risk for ADRD in human populations.

Adolescent intermittent alcohol exposure produces strain-specific cross-sensitization to nicotine and other behavioral adaptations in adulthood in C57BL/6J and DBA/2J mice.

Adolescent alcohol exposure is associated with lasting behavioral changes in humans and in mice. Prior work from our laboratory and others have demonstrated that C57BL/6J and DBA/2J mice differ in sensitivity to some effects of acute alcohol exposure during adolescence and adulthood. However, it is unknown if these strains differ in cognitive, anxiety-related, and addiction-related long-term consequences of adolescent intermittent alcohol exposure.

Interstrain differences in adolescent fear conditioning after acute alcohol exposure.

Adolescent sensitivity to alcohol is a predictor of continued alcohol use and misuse later in life. Thus, it is important to understand the many factors that can impact alcohol sensitivity. Data from our laboratory suggested that susceptibility to alcohol-associated contextual fear learning deficits varied among adolescent and adult mice from two mouse strains.

Genetic differences in nicotine sensitivity and metabolism in C57BL/6J and NOD/ShiLtJ mouse strains.

Genetic background impacts sensitivity to nicotine's rewarding and aversive effects and metabolism, which influences susceptibility to nicotine addiction. This is important because sensitivity to nicotine influences susceptibility to nicotine addiction. Thus, understanding genetic contribution to nicotine sensitivity can aid in identifying risk factors for nicotine addiction.

Inbred mouse strain differences in alcohol and nicotine addiction-related phenotypes from adolescence to adulthood.

Understanding the genetic basis of a predisposition for nicotine and alcohol use across the lifespan is important for public health efforts because genetic contributions may change with age. However, parsing apart subtle genetic contributions to complex human behaviors is a challenge. Animal models provide the opportunity to study the effects of genetic background and age on drug-related phenotypes, while controlling important experimental variables such as amount and timing of drug exposure.

Genetic Differences in Dorsal Hippocampus Acetylcholinesterase Activity Predict Contextual Fear Learning Across Inbred Mouse Strains.

Learning is a critical behavioral process that is influenced by many neurobiological systems. We and others have reported that acetylcholinergic signaling plays a vital role in learning capabilities, and it is especially important for contextual fear learning. Since cholinergic signaling is affected by genetic background, we examined the genetic relationship between activity levels of acetylcholinesterase (AChE), the primary enzyme involved in the acetylcholine metabolism, and learning using a panel of 20 inbred mouse strains.

Gene Cluster Variants Predict Liver Telomere Length in Mice.

Variants in a gene cluster upstream-adjacent to on human chromosome 3, which includes genes , , and , have been associated with telomere length in several human populations. Currently, the mechanism by which variants in the gene cluster influence telomere length in humans is unknown. Given the proximity between the gene cluster and (~0.

Systems genetic analysis of nicotine withdrawal deficits in hippocampus-dependent learning.

Cognitive deficits, such as disrupted learning, are a major symptom of nicotine withdrawal. These deficits are heritable, yet their genetic basis is largely unknown. Our lab has developed a mouse model of nicotine withdrawal deficits in learning, using chronic nicotine exposure via osmotic minipumps and fear conditioning.

Multigenerational nicotine exposure affects offspring nicotine metabolism, nicotine-induced hypothermia, and basal corticosterone in a sex-dependent manner.

Parental nicotine exposure can impact phenotypes in unexposed offspring. Our laboratory recently published data showing that nicotine reward and hippocampal gene expression involved in stress pathways were perturbed in F1 offspring of male C57BL/6J mice chronically exposed to nicotine. For the current study, we aimed to further test nicotine and stress-sensitivity phenotypes that may predict vulnerability to nicotine addiction in new cohorts of F1 offspring derived from nicotine-exposed males.

The effects of adolescent alcohol exposure on learning and related neurobiology in humans and rodents.

Adolescent alcohol use is a widespread problem in the United States. In both humans and rodents, alcohol can impair learning and memory processes mediated by forebrain areas such as the prefrontal cortex (PFC) and hippocampus (HC). Adolescence is a period in which alcohol use often begins, and it is also a time that can be uniquely sensitive to the detrimental effects of alcohol.

Palatable food reduces anxiety-like behaviors and HPA axis responses to stress in female rats in an estrous-cycle specific manner.

Eating tasty foods dampens responses to stress - an idea reflected in the colloquial term 'comfort foods'. To study the neurobiological mechanisms by which palatable foods provide stress relief, we previously characterized a limited sucrose intake (LSI) paradigm in which male rats are given twice-daily access to 4 ml of 30% sucrose solution (vs. water as a control), and subsequently have reduced hypothalamic-pituitary-adrenocortical (HPA) axis responsivity and anxiety-related behaviors.