Faculty Mentors and Program Participants
The common research goal of all of the Behavioral Neuroscience faculty is to advance understanding of the biological basis of behavior and cognition. In pursuit of this objective, the faculty listed below use a wide variety of methods including experimental analysis of animal behavior, in vivo neurochemical and electrophysiological measures, and psychopharmacological interventions. Select topics of interest include the neurophysiology of drug and alcohol addiction, genetic basis of behavior, neural substrates of social behavior, executive function, and motivation. Research is highly collaborative. See below to learn more about the planned research projects of each of the faculty mentor. You can also click on each faculty mentor’s name to be redirected to their faculty page.
Melloni Cook – Dr. Cook’s lab examines the genetic basis of complex traits. As a member of Complex Trait Consortium and the Tennessee Mouse Genome Consortium, Dr. Cook and colleagues have identified gene networks involved in alcohol and stress responses. Dr. Cook’s lab utilizes a range of behavioral techniques (open field, fear extinction, light/dark box, elevated plus maze, tail suspension tests) in inbred mouse strains and genetically modified mice to help identify genetic influences and resulting pathologies related to disorders such as anxiety, post-traumatic stress disorder (PTSD), substance use disorder, schizophrenia, and depression. Current and upcoming projects in Dr. Cook’s lab are focused on characterizing strain effects on behaviors related to PTSD. The genetic underpinnings of PTSD have not been fully explored, and novel mutant mouse strains that express symptoms of PTSD are being pursued. Dr. Cook’s lab is currently comparing such behavioral responses in C57BL/6J (B6) and DBA/2J (D2) inbred mouse strains that differ in learning and memory- and in fear-related paradigms, anxiety-related behaviors, and stress responses. B6 and D2 strains are the parental strains of the largest extant recombinant inbred mouse panel (the BXD RI strains) which will be used in upcoming studies in Dr. Cook’s lab. BXD strains present a variety of phenotypes and have been used for over 25 years to map Mendelian and quantitative trait loci; however, few researchers have characterized BXD mice on PTSD phenotypes. Students in Dr. Cook’s lab will gain experience in animal husbandry, genotyping, the above-mentioned behavioral assays, and complex data analysis. Identifying genetic markers of psychological disorders allows for the creation of clinically relevant animal models and a better understanding of neuropathologies and treatments.
Deranda Lester –Dr. Lester’s lab examines presynaptic mechanisms, neurotransmitter interactions, and neural pathways that influence dopamine transmission. Dopamine regulates behaviors associated with action- selection in the striatum, reward in the nucleus accumbens, emotional processing and anxiety in the amygdala, and executive functioning in the medial prefrontal cortex. The electrochemical technique fixed potential amperometry utilized in Dr. Lester’s lab allows for real-time, subsecond (10k samples/sec) measurement of stimulation-evoked dopamine in anesthetized animals. A recent publication from her lab was the first to characterize and compare specific aspects of phasic dopamine transmission in all of the previously mentioned brain areas. Many projects in Dr. Lester’s lab focus on deciphering the influence of other neurotransmitter systems (such as glutamate, acetylcholine, oxytocin, opioid, and endocannabinoids) on dopamine release and related behaviors. For example, by microinfusing drugs that act on glutamate and/or acetylcholine receptors into the regions containing dopamine cell bodies during in vivo dopamine recordings in the limbic regions, Dr. Lester and colleagues were able to determine the relative contribution of each receptor type. A majority of her current and upcoming projects are centered around understanding the neural interactions between oxytocin and dopamine. A recent publication from her lab was the first to show that systemic administration of oxytocin alters dopamine transmission. Specifically, subchronic oxytocin administration decreased dopamine release and attenuated the dopaminergic response to a psychostimulant in mice. Upcoming projects will examine the effect of oxytocin administration on dopamine transmission in mouse models of addiction and anxiety. Also, direct infusions of oxytocin or oxytocin antagonists into specific brain regions during dopamine recordings will allow for improved understanding of the neural circuitry and mechanisms involved in regulating these interactive effects. Such projects are of particular importance given the interest in oxytocin as a treatment for disorders such as substance use disorder, anxiety, depression, and schizophrenia. Students in Dr. Lester’s lab will be trained in construction and calibration of carbon fiber electrodes, stereotaxic surgery in mice, in vivo amperometric recordings, histology, stereology, brain dissection, and data analysis.
Helen Sable – Dr. Sable’s lab is particularly focused on the DoHAD hypothesis – The Developmental Origins of Health and Disease. More specifically, she examines how negative early life events impact hormonal function, neurochemistry (including deficits in dopamine pharmacology), and behavior and how these neurobiological changes contribute to externalizing behavior/disorders later in life. One leg of her research arm is focused on examining behavioral phenotypes of genetic and environmental (toxin-exposed) rat models of ADHD and substance use disorder. For example, an ongoing collaboration with Cincinnati Children’s Medical Center is assessing behavioral and neurochemical outcomes in Lphn3-/- (i.e., knockout) rats to determine their utility as an animal model of ADHD and substance use disorder. These results are being compared to the same outcomes in the SHR rat (routinely used as an ADHD animal model), and rats exposed in utero to neurotoxicants (e.g., PCBs) her lab has previously shown to increase impulsivity and addiction-related behavior. Students engaged in this arm will learn how to design, conduct, and analyze behavioral tests designed to assess attention and impulsivity as well as drug reinforcement and drug-seeking. A second leg of Dr. Sable’s research will be examining the impact of marijuana use during pregnancy of externalizing behavior of the offspring. Several prospective longitudinal clinical studies report executive function deficits such as impulsivity and inattention and externalizing behaviors including hyperactivity and substance use in children and young adults whose mothers used marijuana once or more per week while pregnant. Dr. Sable will expose female rats to the primary psychoactive constituent of marijuana, delta-9-tetrahydro-cannabinol (Δ9-THC) before, during, and after pregnancy (during lactation) to examine how the timing of Δ9-THC exposure during early development affects executive function and externalizing behavior in adulthood. Students working on these projects will gain technical computer programming experience including working with MedState notation (operant programs), as well as coding in MatLab and Perl (data consolidation). They will also learn how to perform rodent survival surgeries (intravenous jugular catheters), administer intravenous drug infusions, and conduct preconceptional and perinatal dosing in the dams.
Nicholas Simon – Dr. Simon’s lab investigates the neurobiological basis of cost/benefit decision-making in a rat model. One behavioral pattern reliably observed in addiction is risky decision-making, operationalized as persistent choice of risky rewards despite the high likelihood of negative outcomes. Dr. Simon and colleagues have established a behavioral paradigm called the Risky Decision-making Task (RDT) that measures rat preference between small, safe rewards and larger rewards associated with a risk of punishment (mild shock) that escalates throughout a session. Critically, the RDT differs from other commonly used risky decision-making protocols, which utilize loss of reward opportunity rather than physical punishment as a risk factor. NeuroSTART students will contribute to a variety of ongoing projects examining dopamine receptor regulation of risk-taking, the role of amygdalo-cortical circuits in sensitivity to delayed outcomes, and neural encoding of decision-making across the lifespan. Students in Dr. Simon’s lab will gain experience in rat handling, a multitude of rat behavioral assays, data entry and analysis, stereotaxic implantation surgery, brain sectioning and staining, single unit electrophysiology, and optogenetics. Delineating the neurobiological mechanisms underlying risky decision-making has utility for the treatment and prevention of addiction.
2021 NeuroSTART students (L to R): Arrington Moses (Rhodes College), Tyler Feddema (Rhodes College), Lauren Clark (Rhodes College), Ivan Aguilar (University of Memphis), Erielle Culp (LeMoyne-Owen College), Asiah Bounmy (University of Memphis), Alexandria Martin (Christian Brothers University), and Ashlee Sayger (University of Memphis)
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