Medical Sciences Commons^™

Chronic Stress Prevents Cortico-Accumbens Cue Encoding And Alters Conditioned Approach, Mitchell Spring, Aaron Caccamise, Elizabeth A. Panther, Bethany M. Windsor, Karan R. Soni, Jayme R. Mcreynolds, Daniel S. Wheeler, John R. Mantsch, Robert A. Wheeler

Biomedical Sciences Faculty Research and Publications

Chronic stress impairs the function of multiple brain regions and causes severe hedonic and motivational deficits. One brain region known to be susceptible to these effects is the PFC. Neurons in this region, specifically neuronal projections from the prelimbic region (PL) to the nucleus accumbens core (NAcC), have a significant role in promoting motivated approach. However, little is known about how activity in this pathway changes during associative learning to encode cues that promote approach. Less is known about how activity in this pathway may be altered by stress. In this study, an intersectional fiber photometry approach was used in …

Intracellular Β1-Adrenergic Receptors And Organic Cation Transporter 3 Mediate Phospholamban Phosphorylation To Enhance Cardiac Contractility, Ying Wang, Qian Shi, Minghui Li, Meimi Zhao, Raghavender Reddy Gopireddy, Jian-Peng Teoh, Bing Xu, Chaoqun Zhu, Kyle E. Ireton, Sanghavi Srinivasan, Shaoliang Chen, Paul J. Gasser, Julie Bossuyt, Johannes W. Hell, Donald M. Bers, Yang K. Xiang

Biomedical Sciences Faculty Research and Publications

Rationale:

β₁ARs (β₁-adrenoceptors) exist at intracellular membranes and OCT3 (organic cation transporter 3) mediates norepinephrine entry into cardiomyocytes. However, the functional role of intracellular β₁AR in cardiac contractility remains to be elucidated.

Objective:

Test localization and function of intracellular β₁AR on cardiac contractility.

Methods and Results:

Membrane fractionation, super-resolution imaging, proximity ligation, coimmunoprecipitation, and single-molecule pull-down demonstrated a pool of β₁ARs in mouse hearts that were associated with sarco/endoplasmic reticulum Ca²⁺-ATPase at the sarcoplasmic reticulum (SR). Local PKA (protein kinase A) activation was measured using a PKA biosensor …

Vasopressin Regulates Daily Rhythms And Circadian Clock Circuits In A Manner Influenced By Sex, Kayla Rohr, Adam Telega, Alexandra Savaglio, Jennifer A. Evans

Biomedical Sciences Faculty Research and Publications

Arginine vasopressin (AVP) is a neurohormone that alters cellular physiology through both endocrine and synaptic signaling. Circadian rhythms in AVP release and other biological processes are driven by the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. Loss of vasopressin signaling alters circadian behavior, but the basis of these effects remains unclear. Here we investigate the role of AVP signaling in circadian timekeeping by analyzing behavior and SCN function in a novel AVP-deficient mouse model. Consistent with previous work, loss of AVP signaling increases water consumption and accelerates recovery to simulated jetlag. We expand on these results to show that loss …

Organic Cation Transporter 3 And The Dopamine Transporter Differentially Regulate Catecholamine Uptake In The Basolateral Amygdala And Nucleus Accumbens, Katherine M. Holleran, Jamie H. Rose, Steven C. Fordahl, Kelsey C. Benton, Kayla E. Rohr, Paul J. Gasser, Sara R. Jones

Biomedical Sciences Faculty Research and Publications

Regional alterations in kinetics of catecholamine uptake are due in part to variations in clearance mechanisms. The rate of clearance is a critical determinant of the strength of catecholamine signaling. Catecholamine transmission in the nucleus accumbens core (NAcc) and basolateral amygdala (BLA) is of particular interest due to involvement of these regions in cognition and motivation. Previous work has shown that catecholamine clearance in the NAcc is largely mediated by the dopamine transporter (DAT), but clearance in the BLA is less DAT‐dependent. A growing body of literature suggests that organic cation transporter 3 (OCT3) also contributes to catecholamine clearance in …

Marking Time: Colorful New Insights Into Master Clock Circuits, Deborah A.M. Joye, Jennifer A. Evans

Biomedical Sciences Faculty Research and Publications

No abstract provided.

Neurotoxicity Of Isomers Of The Environmental Toxin L-Bmaa, Thomas Schneider, Catherine Simpson, Prachi Desai, Madeleine Tucker, Doug Lobner

Biomedical Sciences Faculty Research and Publications

There is evidence that the environmental toxin β-N-methylamino-L-alanine (L-BMAA) may be involved in neurodegenerative diseases. However, a number of controversies exist regarding L-BMAA, one of which is the possibility that when assaying for L-BMAA, its isomers are being detected instead. There are at least four isomers of BMAA that are known to occur: L-BMAA, β-N-methylamino-D-alanine (D-BMAA), 2,4-diaminobutyric acid (DAB), and N-(2-aminoethyl)glycine (AEG). The fact that isomers of BMAA exist in nature also leads to the possibility that they are involved in toxicity. We set out to determine both the potency and the mechanism of toxicity of L-BMAA, D-BMAA, DAB, and …

Reduced Vip Expression Affects Circadian Clock Function In Vip-Ires-Cre Mice (Jax 010908), Deborah A.M. Joye, Kayla Rohr, Danielle Keller, Thomas Inda, Adam Telega, Harshida Pancholi, Vania Carmonia-Alcocer, Jennifer A. Evans

Biomedical Sciences Faculty Research and Publications

Circadian rhythms are programmed by the suprachiasmatic nucleus (SCN), which relies on neuropeptide signaling to maintain daily timekeeping. Vasoactive intestinal polypeptide (VIP) is critical for SCN function, but the precise role of VIP neurons in SCN circuits is not fully established. To interrogate their contribution to SCN circuits, VIP neurons can be manipulated specifically using the DNA-editing enzyme Cre recombinase. Although the Cre transgene is assumed to be inert by itself, we find that VIP expression is reduced in both heterozygous and homozygous adult VIP-IRES-Cre mice (JAX 010908). Compared with wild-type mice, homozygous VIP-Cre mice display faster reentrainment and shorter …

Prelimbic Input To Basolateral Amygdala Facilitates The Acquisition Of Trace Cued Fear Memory Under Weak Training Conditions, Adam Kirry, Robert C. Twining, Marieke R. Gilmartin

Biomedical Sciences Faculty Research and Publications

The ability to predict the occurrence of an aversive outcome based on available cues requires associative learning and plastic changes in the amygdala. When the predictive cue and aversive shock outcome are separated in time as in trace fear conditioning, additional circuitry is needed, including the prelimbic (PL) area of the prefrontal cortex. We have previously shown that neuronal firing in the PL during the trace interval separating the cue and shock is required for trace cued fear memory formation, but whether this mnemonic signal is conveyed to the amygdala is unknown. Here we show in males that silencing PL …

Predictors Of In-Hospital Mortality Among Under-Five Children With Severe Acute Malnutrition In South-Western Uganda, Timothy Nduhukire, Daniel Atwine, Luwaga Rachel, Joseph Byonanebye

Biomedical Sciences Faculty Research and Publications

Background

Severe acute malnutrition (SAM) affects about 13 million under-five children (U5), with an estimated one million dying every year. In this study we aimed at determining the in hospital mortality and its associated factors among U5s admitted with SAM.

Methods

This was a prospective cohort study of children 6 months to 5 years with SAM admitted at Mbarara Regional Referral Hospital (MRRH) between June and August 2015. Care-takers were interviewed to collect socio-demographic and clinical information. Children under-went physical examination and had blood drawn for HIV, serum glucose, malaria, full blood count, culture and serum electrolytes investigation. Children were …

Sex, Stress, And Prefrontal Cortex: Influence Of Biological Sex On Stress-Promoted Cocaine Seeking, Elizabeth M. Doncheck, Gage T. Liddiard, Chaz D. Konrath, Xiaojie Liu, Laikang Yu, Luke A. Urbanik, Matthew R. Herbst, Margot C. Debaker, Nicholas J. Raddatz, Erik C. Van Newenhizen, Jacob Mathy, Marieke R. Gilmartin, Qing-Song Liu, Cecilia J. Hillard, John Mantsch

Biomedical Sciences Faculty Research and Publications

Clinical reports suggest that females diagnosed with substance use disorder experience enhanced relapse vulnerability compared with males, particularly during stress. We previously demonstrated that a stressor (footshock) can potentiate cocaine seeking in male rats via glucocorticoid-dependent cannabinoid type-1 receptor (CB1R)-mediated actions in the prelimbic prefrontal cortex (PrL-PFC). Here, we investigated the influence of biological sex on stress-potentiated cocaine seeking. Despite comparable self-administration and extinction, females displayed a lower threshold for cocaine-primed reinstatement than males. Unlike males, footshock, tested across a range of intensities, failed to potentiate cocaine-primed reinstatement in females. However, restraint potentiated reinstatement in both sexes. While sex differences …

Acute Blockade Of Pacap-Dependent Activity In The Ventromedial Nucleus Of The Hypothalamus Disrupts Leptin-Induced Behavioral And Molecular Changes In Rats, Matthew M. Hurley, Eden M. Anderson, Christopher Chen, Brian Maunze, Evan Michael Hess, Megan E. Block, Neerali Patel, Zane Cooper, Riley Mccoy, Tanya Dabra, William Conley, Michael J. Reilly, Matthew C. Hearing, Sujean Choi

Biomedical Sciences Faculty Research and Publications

Leptin signaling pathways, stemming primarily from the hypothalamus, are necessary for maintaining normal energy homeostasis and body weight. In both rodents and humans, dysregulation of leptin signaling leads to morbid obesity and diabetes. Since leptin resistance is considered a primary factor underlying obesity, understanding the regulation of leptin signaling could lead to therapeutic tools and provide insights into the causality of obesity. While leptin actions in some hypothalamic regions such as the arcuate nuclei have been characterized, less is known about leptin activity in the hypothalamic ventromedial nuclei (VMN). Recently, pituitary adenylate cyclase activating-polypeptide (PACAP) has been shown to reduce …

Circuit Development In The Master Clock Network Of Mammals, Vania Carmonia-Alcocer, Kayla Rohr, Deborah A.M. Joye, Jennifer A. Evans

Biomedical Sciences Faculty Research and Publications

Daily rhythms are generated by the circadian timekeeping system, which is orchestrated by the master circadian clock in the suprachiasmatic nucleus (SCN) of mammals. Circadian timekeeping is endogenous and does not require exposure to external cues during development. Nevertheless, the circadian system is not fully formed at birth in many mammalian species and it is important to understand how SCN development can affect the function of the circadian system in adulthood. The purpose of the current review is to discuss the ontogeny of cellular and circuit function in the SCN, with a focus on work performed in model rodent species …

Seasonal Plasticity In GabaA Signaling Is Necessary For Restoring Phase Synchrony In The Master Circadian Clock Network, Kayla Rohr, Harshida Pancholi, Shabi Haider, Christopher Karow, David Modert, Nicholas J. Raddatz, Jennifer A. Evans

Biomedical Sciences Faculty Research and Publications

Annual changes in the environment threaten survival, and numerous biological processes in mammals adjust to this challenge via seasonal encoding by the suprachiasmatic nucleus (SCN). To tune behavior according to day length, SCN neurons display unified rhythms with synchronous phasing when days are short, but will divide into two sub-clusters when days are long. The transition between SCN states is critical for maintaining behavioral responses to seasonal change, but the mechanisms regulating this form of neuroplasticity remain unclear. Here we identify that a switch in chloride transport and GABA_A signaling is critical for maintaining state plasticity in the SCN …

Circuit-Specific Control Of The Medial Entorhinal Inputs To The Dentate Gyrus By Atypical Presynaptic Nmdars Activated By Astrocytes, Iaroslav Savtchouk, Maria Amalia Di Castro, Rugina Ali, Hiltrud Stubbe, Rafael Lujan, Andrea Volterra

Biomedical Sciences Faculty Research and Publications

Here, we investigated the properties of presynaptic N-methyl-D-aspartate receptors (pre-NMDARs) at corticohippocampal excitatory connections between perforant path (PP) afferents and dentate granule cells (GCs), a circuit involved in memory encoding and centrally affected in Alzheimer’s disease and temporal lobe epilepsy. These receptors were previously reported to increase PP release probability in response to gliotransmitters released from astrocytes. Their activation occurred even under conditions of elevated Mg²⁺ and lack of action potential firing in the axons, although how this could be accomplished was unclear. We now report that these pre-NMDARs contain the GluN3a subunit conferring them low Mg^{2+ …}

Enhancing Cell Seeding And Osteogenesis Of Mscs On 3d Printed Scaffolds Through Injectable Bmp2 Immobilized Ecm-Mimetic Gel, Farahnaz Fahimipour, Erfan Dashtimoghadam, Mohammad Mahdi Hasani-Sadrabadi, Jessica Vargas, Daryoosh Vashaee, Doug Lobner, Tahereh S. Jafarzadeh Kashi, Behnam Ghasemzadeh, Lobat Tayebi

Biomedical Sciences Faculty Research and Publications

Objective

Design of bioactive scaffolds with osteogenic capacity is a central challenge in cell-based patient-specific bone tissue engineering. Efficient and spatially uniform seeding of (stem) cells onto such constructs is vital to attain functional tissues. Herein we developed heparin functionalized collagen gels supported by 3D printed bioceramic scaffolds, as bone extracellular matrix (ECM)-mimetic matrices. These matrices were designed to enhance cell seeding efficiency of mesenchymal stem cells (MSCs) as well as improve their osteogenic differentiation through immobilized bone morphogenic protein 2 (BMP2) to be used for personalized bone regeneration.

Methods

A 3D gel based on heparin-conjugated collagen matrix capable of …

Positions In The N‐Methyl‐D‐Aspartate Receptor Glun2c Subunit M3 And M4 Domains Regulate Alcohol Sensitivity And Receptor Kinetics, Man Wu, Priya Katti, Yulin Zhao, Robert W. Peoples

Biomedical Sciences Faculty Research and Publications

Background

Alcohol alters synaptic transmission in the brain. The N‐methyl‐D‐aspartate (NMDA) receptor (NMDAR), a subtype of glutamate‐gated ion channel, is an important synaptic target of alcohol in the brain. We and others have previously identified 4 alcohol‐sensitive positions in the third and fourth membrane‐associated (M) domains, designated M3_1‐2and M4_1‐2, of the GluN1, GluN2A, and GluN2B NMDAR subunits. In the present study, we tested whether the corresponding positions in the GluN2C subunit also regulate alcohol sensitivity and ion channel gating.

Methods

We performed alanine‐ and tryptophan‐scanning mutagenesis in the GluN2C subunit followed by expression in HEK …

Roles For The Uptake2 Transporter Oct3 In Regulation Of Dopaminergic Neurotransmission And Behavior, Paul J. Gasser

Biomedical Sciences Faculty Research and Publications

Transporter-mediated uptake determines the peak concentration, duration, and physical spread of released monoamines. Most studies of monoamine clearance focus on the presynaptic uptake₁ transporters SERT, NET and DAT. However, recent studies have demonstrated the expression of the uptake₂ transporter OCT3 (organic cation transporter 3), throughout the rodent brain. In contrast to NET, DAT and SERT, OCT3 has higher capacity and lower affinity for substrates, is sodium-independent, and is multi-specific, with the capacity to transport norepinephrine, dopamine, serotonin and histamine. OCT3is insensitive to inhibition by cocaine and antidepressant drugs but is inhibited directly by the glucocorticoid hormone corticosterone. Thus, …

Mental Imagery Practice As A Therapy For Naming Impairments: A Preliminary Study, Subhash Bhatnagar, Bridget Patek, Yasmeen Khan-Ansari, Naveen K. Bansal, Hugh Buckingham, Lotfi Hacein-Bey

Speech Pathology and Audiology Faculty Research and Publications

Background

Anomia remains one of the most recalcitrant linguistic disruptions in aphasia to treat. Developing successful interventions to address the word-finding deficits are complicated by the post-stroke symptom variability and inconsistent recovery patterns associated with anomia. Most of the current treatment methods, with a focus on specific compensating techniques and the repetitive practice of a limited set of items, have had variable success in naming treatment. However, it has not been possible to predict the gains in generalizing the learning beyond the stimuli used in practice or the controlled clinical setting. In this preliminary case study, we explore the value …

Mice, Acorns, And Lyme Disease: A Case Study To Teach The Ecology Of Emerging Infectious Diseases, Laurieann Klockow

Biomedical Sciences Faculty Research and Publications

Ebola, Zika, the recall of contaminated lettuce - these are just a few recent outbreaks making headlines. Students should be able to connect what they learn in their biology courses to explain these events happening around them. Unfortunately, students do not necessarily make those connections. Therefore, it is important, as instructors, to provide opportunities where students engage with societal issues and problems related to course content and case studies, using headlines from the news are one way to do this.

Here I describe a case study about Lyme disease that engages students in learning about the ecology of infectious disease. …

Determinants Of Occupational Injuries Among Building Construction Workers In Kampala City, Uganda, Arthur Kiconco, Nathan Ruhinda, Abdullah Ali Halage, Stephen Watya, William Bazeyo, John C. Ssempebwa, Joseph Byonanebye

Biomedical Sciences Faculty Research and Publications

Background

Globally, about 1000 people die and close to 860,000 people sustain injury at work daily. Injury prevention and control require contextual evidence, although most studies in Uganda have focused on general causes. Factors associated with occupational injuries among building construction workers were assessed in this study.

Methods

A cross-sectional study among building construction workers was conducted in Kampala, Uganda. A standardized semi-structured questionnaire was used to collect data. Three hundred nineteen (319) participants were randomly and proportionately selected from 57 construction sites. Descriptive statistics were used to describe the variables while generalized linear modeling was used to estimate the …

Prefrontal-Accumbens Opioid Plasticity: Implications For Relapse And Dependence, Matthew C. Hearing

Biomedical Sciences Faculty Research and Publications

In addiction, an individual’s ability to inhibit drug seeking and drug taking is thought to reflect a pathological strengthening of drug-seeking behaviors or impairments in the capacity to control maladaptive behavior. These processes are not mutually exclusive and reflect drug-induced modifications within prefrontal cortical and nucleus accumbens circuits, however unlike psychostimulants such as cocaine, far less is known about the temporal, anatomical, and cellular dynamics of these changes. We discuss what is known regarding opioid-induced adaptations in intrinsic membrane physiology and pre-/postsynaptic neurotransmission in principle pyramidal and medium spiny neurons in the medial prefrontal cortex and nucleus accumbens from electrophysiological …

Global Connectivity And Function Of Descending Spinal Input Revealed By 3d Microscopy And Retrograde Transduction, Zimei Wang, Brian Maunze, Yunfang Wang, Pantelis Tsoulfas, Murray G. Blackmore

Biomedical Sciences Faculty Research and Publications

The brain communicates with the spinal cord through numerous axon tracts that arise from discrete nuclei, transmit distinct functions, and often collateralize to facilitate the coordination of descending commands. This complexity presents a major challenge to interpreting functional outcomes from therapies that target supraspinal connectivity after injury or disease, while the wide distribution of supraspinal nuclei complicates the delivery of therapeutics. Here we harness retrograde viral vectors to overcome these challenges. We demonstrate that injection of AAV2-Retro to the cervical spinal cord of adult female mice results in highly efficient transduction of supraspinal populations throughout the brainstem, midbrain, and cortex. …

Changes In Electroencephalogram Coherence In Adolescents With Autism Spectrum Disorder After A Social Skills Intervention, Angela D. Haendel

Dissertations (1934 -)

Autism spectrum disorder (ASD) is a developmental disorder that affects social communication and behavior. There is a consensus that neurological differences present in individuals with ASD. Further, theories emphasize the mixture of hypo- and hyper-connectivity as a neuropathology in ASD (O’Reilly, Lewis, & Elsabbagh, 2017), however, there is a paucity of studies specifically testing neurological underpinnings as predictors of success on social skills interventions. This study examined functional neural connectivity (electroencephalogram, EEG, coherence) of adolescents with ASD before and after the Program for the Education and Enrichment of Relational Skills (PEERS®) intervention. Two groups were utilized in this randomized controlled …

Developmental Chromatin Restriction Of Pro‐Growth Gene Networks Acts As An Epigenetic Barrier To Axon Regeneration In Cortical Neurons, Ishwariya Venkatesh, Vatsal Mehra, Zimei Wang, Ben Califf, Murray G. Blackmore

Biomedical Sciences Faculty Research and Publications

Axon regeneration in the central nervous system is prevented in part by a developmental decline in the intrinsic regenerative ability of maturing neurons. This loss of axon growth ability likely reflects widespread changes in gene expression, but the mechanisms that drive this shift remain unclear. Chromatin accessibility has emerged as a key regulatory mechanism in other cellular contexts, raising the possibility that chromatin structure may contribute to the age‐dependent loss of regenerative potential. Here we establish an integrated bioinformatic pipeline that combines analysis of developmentally dynamic gene networks with transcription factor regulation and genome‐wide maps of chromatin accessibility. When applied …

Organic Cation Transporter 3: A Cellular Mechanism Underlying Rapid, Non-Genomic Glucocorticoid Regulation Of Monoaminergic Neurotransmission, Physiology, And Behavior, Paul J. Gasser, Christopher A. Lowry

Biomedical Sciences Faculty Research and Publications

Corticosteroid hormones act at intracellular glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) to alter gene expression, leading to diverse physiological and behavioral responses. In addition to these classical genomic effects, corticosteroid hormones also exert rapid actions on physiology and behavior through a variety of non-genomic mechanisms, some of which involve GR or MR, and others of which are independent of these receptors. One such GR-independent mechanism involves corticosteroid-induced inhibition of monoamine transport mediated by “uptake₂” transporters, including organic cation transporter 3 (OCT3), a low-affinity, high-capacity transporter for norepinephrine, epinephrine, dopamine, serotonin and histamine. Corticosterone directly and acutely inhibits …

Pituitary Adenylate Cyclase-Activating Polypeptide (Pacap) Signaling In The Prefrontal Cortex Modulates Cued Fear Learning, But Not Spatial Working Memory, In Female Rats, Adam J. Kirry, Matthew R. Herbst, Sarah E. Poirier, Michelle M. Maskeri, Amy C. Rothwell, Robert C. Twining, Marieke R. Gilmartin

Biomedical Sciences Faculty Research and Publications

A genetic polymorphism within the gene encoding the pituitary adenylate cyclase- activating polypeptide (PACAP) receptor type I (PAC1R) has recently been associated with hyper-reactivity to threat-related cues in women, but not men, with post-traumatic stress disorder (PTSD). PACAP is a highly conserved peptide, whose role in mediating adaptive physiological stress responses is well established. Far less is understood about the contribution of PACAP signaling in emotional learning and memory, particularly the encoding of fear to discrete cues. Moreover, a neurobiological substrate that may account for the observed link between PAC1R and PTSD in women, but not men, has yet to …

Endogenous Dopamine And Endocannabinoid Signaling Mediate Cocaine-Induced Reversal Of Ampar Synaptic Potentiation In The Nucleus Accumbens Shell, Anna E. Ingebretson, Matthew C. Hearing, Ethan D. Huffington, Mark J. Thomas

Biomedical Sciences Faculty Research and Publications

Repeated exposure to drugs of abuse alters the structure and function of neural circuits mediating reward, generating maladaptive plasticity in circuits critical for motivated behavior. Within meso-corticolimbic dopamine circuitry, repeated exposure to cocaine induces progressive alterations in AMPAR-mediated glutamatergic synaptic transmission. During a 10–14 day period of abstinence from cocaine, AMPAR signaling is potentiated at synapses on nucleus accumbens (NAc) medium spiny neurons (MSNs), promoting a state of heightened synaptic excitability. Re-exposure to cocaine during abstinence, however, rapidly reverses and depotentiates enhanced AMPAR signaling. To understand how re-exposure to cocaine alters AMPAR synaptic transmission, we investigated the roles of dopamine …

Kappa Counterconditioning Of Cocaine Cues, John R. Mantsch, Robert C. Twining

Biomedical Sciences Faculty Research and Publications

No abstract provided.

Klf6 And Stat3 Co-Occupy Regulatory Dna And Functionally Synergize To Promote Axon Growth In Cns Neurons, Zimei Wang, Vatsal Mehra, Matthew T. Simpson, Brian Maunze, Dan C. Eastwood, Lyndsey Holan, Murray G. Blackmore, Ishwariya Venkatesh

Biomedical Sciences Faculty Research and Publications

The failure of axon regeneration in the CNS limits recovery from damage and disease. Members of the KLF family of transcription factors can exert both positive and negative effects on axon regeneration, but the underlying mechanisms are unclear. Here we show that forced expression of KLF6 promotes axon regeneration by corticospinal tract neurons in the injured spinal cord. RNA sequencing identified 454 genes whose expression changed upon forced KLF6 expression in vitro, including sub-networks that were highly enriched for functions relevant to axon extension including cytoskeleton remodeling, lipid synthesis, and bioenergetics. In addition, promoter analysis predicted a functional interaction …

What Does The Fos Say? Using Fos-Based Approaches To Understand The Contribution Of Stress To Substance Use Disorders, Jayme R. Mcreynolds, John P. Christianson, Jordan M. Blacktop, John Mantsch

Biomedical Sciences Faculty Research and Publications

Despite extensive research efforts, drug addiction persists as a largely unmet medical need. Perhaps the biggest challenge for treating addiction is the high rate of recidivism. While many factors can promote relapse in abstinent drug users, the contribution of stress is particularly problematic, as stress is uncontrollable and pervasive in the lives of those struggling with addiction. Thus, understanding the neurocircuitry that underlies the influence of stress on drug seeking is critical for guiding treatment. Preclinical research aimed at defining this neurocircuitry has, in part, relied upon the use of experimental approaches that allow visualization of cellular and circuit activity …