Medicine and Health Sciences | Open Access Articles

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. …

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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 …

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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 …

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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 …

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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 …

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

Biomedical Sciences Faculty Research and Publications

No abstract provided.

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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 …

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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 …

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17Β-Estradiol Potentiates The Reinstatement Of Cocaine Seeking In Female Rats: Role Of The Prelimbic Prefrontal Cortex And Cannabinoid Type-1 Receptors, Elizabeth M. Doncheck, Luke A. Urbanik, Margot C. Debaker, Laura M. Barron, Gage T. Liddiard, Jennifer J. Tuscher, Karyn M. Frick, Cecilia J. Hillard, John Mantsch

Biomedical Sciences Faculty Research and Publications

Clinical observations imply that female cocaine addicts experience enhanced relapse vulnerability compared with males, an effect tied to elevated estrogen phases of the ovarian hormone cycle. Although estrogens can enhance drug-seeking behavior, they do not directly induce reinstatement on their own. To model this phenomenon, we tested whether an estrogen could augment drug-seeking behavior in response to an ordinarily subthreshold reinstatement trigger. Following cocaine self-administration and extinction, female rats were ovariectomized to isolate estrogen effects on reinstatement. Although neither peak proestrus levels of the primary estrogen 17β-estradiol (E2; 10 μg/kg, i.p., 1-h pretreatment) nor a subthreshold cocaine dose …

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Transport Of Bmaa Into Neurons And Astrocytes By System XC-, Rebecca Albano, Doug Lobner

Biomedical Sciences Faculty Research and Publications

The study of the mechanism of β-N-methylamino-l-alanine (BMAA) neurotoxicity originally focused on its effects at the N-methyl-d-aspartate (NMDA) receptor. In recent years, it has become clear that its mechanism of action is more complicated. First, there are certain cell types, such as motor neurons and cholinergic neurons, where the dominate mechanism of toxicity is through action at AMPA receptors. Second, even in cortical neurons where the primary mechanism of toxicity appears to be activation of NMDA receptors, there are other mechanisms involved. We found that along with NMDA receptors, activation of mGLuR5 receptors and effects on the …

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The Opiod Epidemic: Clinical Dental Update, Matthew Hearing

Biomedical Sciences Faculty Research and Publications

No abstract provided.

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Full-Text Articles in Medicine and Health Sciences

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

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

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

Biomedical Sciences Faculty Research and Publications

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

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

Biomedical Sciences Faculty Research and Publications

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

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

Biomedical Sciences Faculty Research and Publications

Transport Of Bmaa Into Neurons And Astrocytes By System XC-, Rebecca Albano, Doug Lobner

Biomedical Sciences Faculty Research and Publications

The Opiod Epidemic: Clinical Dental Update, Matthew Hearing

Biomedical Sciences Faculty Research and Publications