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  1. Article ; Online: An automaton for preclinical pain testing.

    Graham, Robert D / Creed, Meaghan C

    Cell reports methods

    2023  Volume 3, Issue 12, Page(s) 100668

    Abstract: In this issue of Cell Reports Methods, Dedek et al. present RAMalgo-an AI-powered, automated platform for quantifying nociceptive behaviors in mice. With integrated video tracking and mechanical, thermal, and optogenetic stimulation, RAMalgo has the ... ...

    Abstract In this issue of Cell Reports Methods, Dedek et al. present RAMalgo-an AI-powered, automated platform for quantifying nociceptive behaviors in mice. With integrated video tracking and mechanical, thermal, and optogenetic stimulation, RAMalgo has the potential to increase standardization and throughput of pain behavior measurement in rodents.
    MeSH term(s) Mice ; Animals ; Pain/diagnosis ; Pain Measurement/methods
    Language English
    Publishing date 2023-12-11
    Publishing country United States
    Document type Journal Article
    ISSN 2667-2375
    ISSN (online) 2667-2375
    DOI 10.1016/j.crmeth.2023.100668
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  2. Article ; Online: Updating the striatal-pallidal wiring diagram.

    Fang, Lisa Z / Creed, Meaghan C

    Nature neuroscience

    2023  Volume 27, Issue 1, Page(s) 15–27

    Abstract: The striatal and pallidal complexes are basal ganglia structures that orchestrate learning and execution of flexible behavior. Models of how the basal ganglia subserve these functions have evolved considerably, and the advent of optogenetic and molecular ...

    Abstract The striatal and pallidal complexes are basal ganglia structures that orchestrate learning and execution of flexible behavior. Models of how the basal ganglia subserve these functions have evolved considerably, and the advent of optogenetic and molecular tools has shed light on the heterogeneity of subcircuits within these pathways. However, a synthesis of how molecularly diverse neurons integrate into existing models of basal ganglia function is lacking. Here, we provide an overview of the neurochemical and molecular diversity of striatal and pallidal neurons and synthesize recent circuit connectivity studies in rodents that takes this diversity into account. We also highlight anatomical organizational principles that distinguish the dorsal and ventral basal ganglia pathways in rodents. Future work integrating the molecular and anatomical properties of striatal and pallidal subpopulations may resolve controversies regarding basal ganglia network function.
    MeSH term(s) Corpus Striatum ; Globus Pallidus ; Basal Ganglia/physiology ; Neurons ; Neostriatum ; Neural Pathways/physiology
    Language English
    Publishing date 2023-12-06
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1420596-8
    ISSN 1546-1726 ; 1097-6256
    ISSN (online) 1546-1726
    ISSN 1097-6256
    DOI 10.1038/s41593-023-01518-x
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  3. Article ; Online: Invariant inhibition to calculate prediction errors?

    Creed, Meaghan C / Loureiro, Michaël / Lüscher, Christian

    Trends in neurosciences

    2023  Volume 46, Issue 4, Page(s) 257–259

    Abstract: The ventral tegmental area (VTA) has a pivotal role in motivated behavior. Much of the research on the VTA has focused on the mesocorticolimbic dopamine projections and their role in the computation of a 'reward prediction error' (RPE) for reward-guided ... ...

    Abstract The ventral tegmental area (VTA) has a pivotal role in motivated behavior. Much of the research on the VTA has focused on the mesocorticolimbic dopamine projections and their role in the computation of a 'reward prediction error' (RPE) for reward-guided learning. In a recent study, Zhou et al. report that VTA GABA neurons, the axons of which innervate the ventral pallidum (VP), have a unique role in signaling reward value to the basal ganglia and guiding reward seeking.
    MeSH term(s) Humans ; Ventral Tegmental Area/physiology ; Basal Ganglia ; Dopamine ; Reward
    Chemical Substances Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2023-01-26
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 282488-7
    ISSN 1878-108X ; 0378-5912 ; 0166-2236
    ISSN (online) 1878-108X
    ISSN 0378-5912 ; 0166-2236
    DOI 10.1016/j.tins.2023.01.004
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  4. Article ; Online: Toward a targeted treatment for addiction.

    Creed, Meaghan C

    Science (New York, N.Y.)

    2017  Volume 357, Issue 6350, Page(s) 464–465

    Language English
    Publishing date 2017-08-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.aao1197
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  5. Article: Deep Brain Stimulation of the Subthalamic Nucleus Modulates Reward-Related Behavior: A Systematic Review.

    Vachez, Yvan M / Creed, Meaghan C

    Frontiers in human neuroscience

    2020  Volume 14, Page(s) 578564

    Abstract: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for the motor symptoms of movement disorders including Parkinson's Disease (PD). Despite its therapeutic benefits, STN-DBS has been associated with adverse effects on ... ...

    Abstract Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for the motor symptoms of movement disorders including Parkinson's Disease (PD). Despite its therapeutic benefits, STN-DBS has been associated with adverse effects on mood and cognition. Specifically, apathy, which is defined as a loss of motivation, has been reported to emerge or to worsen following STN-DBS. However, it is often challenging to disentangle the effects of STN-DBS
    Language English
    Publishing date 2020-11-20
    Publishing country Switzerland
    Document type Systematic Review
    ZDB-ID 2425477-0
    ISSN 1662-5161
    ISSN 1662-5161
    DOI 10.3389/fnhum.2020.578564
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  6. Article: Impact of Δ

    Slivicki, Richard A / Wang, Justin G / Nhat, Vy Trinh Tran / Kravitz, Alexxai V / Creed, Meaghan C / Gereau, Robert W

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Oxycodone is commonly prescribed for moderate to severe pain disorders. While efficacious, long-term use can result in tolerance, physical dependence, and the development of opioid use disorder. Cannabis and its derivatives such as ... ...

    Abstract Oxycodone is commonly prescribed for moderate to severe pain disorders. While efficacious, long-term use can result in tolerance, physical dependence, and the development of opioid use disorder. Cannabis and its derivatives such as Δ
    Language English
    Publishing date 2023-12-06
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.12.04.569809
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  7. Article: Cell specific single viral vector CRISPR/Cas9 editing and genetically encoded tool delivery in the central and peripheral nervous systems.

    Moffa, Jamie C / Bland, India N / Tooley, Jessica R / Kalyanaraman, Vani / Heitmeier, Monique / Creed, Meaghan C / Copits, Bryan A

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Gene manipulation strategies using germline knockout, conditional knockout, and more recently CRISPR/Cas9 are crucial tools for advancing our understanding of the nervous system. However, traditional gene knockout approaches can be costly and time ... ...

    Abstract Gene manipulation strategies using germline knockout, conditional knockout, and more recently CRISPR/Cas9 are crucial tools for advancing our understanding of the nervous system. However, traditional gene knockout approaches can be costly and time consuming, may lack cell-type specificity, and can induce germline recombination. Viral gene editing presents and an exciting alternative to more rapidly study genes of unknown function; however, current strategies to also manipulate or visualize edited cells are challenging due to the large size of Cas9 proteins and the limited packaging capacity of adeno-associated viruses (AAVs). To overcome these constraints, we have developed an alternative gene editing strategy using a single AAV vector and mouse lines that express Cre-dependent Cas9 to achieve efficient cell-type specific editing across the nervous system. Expressing Cre-dependent Cas9 in specific cell types in transgenic mouse lines affords more space to package guide RNAs for gene editing together with Cre-dependent, genetically encoded tools to manipulate, map, or monitor neurons using a single virus. We validated this strategy with three commonly used tools in neuroscience: ChRonos, a channelrhodopsin, for manipulating synaptic transmission using optogenetics; GCaMP8f for recording Ca2+ transients using fiber photometry, and mCherry for anatomical tracing of axonal projections. We tested these tools in multiple brain regions and cell types, including GABAergic neurons in the nucleus accumbens (NAc), glutamatergic neurons projecting from the ventral pallidum (VP) to the lateral habenula (LHb), dopaminergic neurons in the ventral tegmental area (VTA), and parvalbumin (PV)-positive proprioceptive neurons in the periphery. This flexible approach should be useful to identify novel genes that affect synaptic transmission, circuit activity, or morphology with a single viral injection.
    Language English
    Publishing date 2023-10-10
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.10.10.561249
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  8. Article: The role of endogenous opioid neuropeptides in neurostimulation-driven analgesia.

    Lubejko, Susan T / Graham, Robert D / Livrizzi, Giulia / Schaefer, Robert / Banghart, Matthew R / Creed, Meaghan C

    Frontiers in systems neuroscience

    2022  Volume 16, Page(s) 1044686

    Abstract: Due to the prevalence of chronic pain worldwide, there is an urgent need to improve pain management strategies. While opioid drugs have long been used to treat chronic pain, their use is severely limited by adverse effects and abuse liability. ... ...

    Abstract Due to the prevalence of chronic pain worldwide, there is an urgent need to improve pain management strategies. While opioid drugs have long been used to treat chronic pain, their use is severely limited by adverse effects and abuse liability. Neurostimulation techniques have emerged as a promising option for chronic pain that is refractory to other treatments. While different neurostimulation strategies have been applied to many neural structures implicated in pain processing, there is variability in efficacy between patients, underscoring the need to optimize neurostimulation techniques for use in pain management. This optimization requires a deeper understanding of the mechanisms underlying neurostimulation-induced pain relief. Here, we discuss the most commonly used neurostimulation techniques for treating chronic pain. We present evidence that neurostimulation-induced analgesia is in part driven by the release of endogenous opioids and that this endogenous opioid release is a common endpoint between different methods of neurostimulation. Finally, we introduce technological and clinical innovations that are being explored to optimize neurostimulation techniques for the treatment of pain, including multidisciplinary efforts between neuroscience research and clinical treatment that may refine the efficacy of neurostimulation based on its underlying mechanisms.
    Language English
    Publishing date 2022-12-14
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2453005-0
    ISSN 1662-5137
    ISSN 1662-5137
    DOI 10.3389/fnsys.2022.1044686
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  9. Article ; Online: Orbitofrontal-striatal potentiation underlies cocaine-induced hyperactivity.

    Bariselli, Sebastiano / Miyazaki, Nanami L / Creed, Meaghan C / Kravitz, Alexxai V

    Nature communications

    2020  Volume 11, Issue 1, Page(s) 3996

    Abstract: Psychomotor stimulants increase dopamine levels in the striatum and promote locomotion; however, their effects on striatal pathway function in vivo remain unclear. One model that has been proposed to account for these motor effects suggests that ... ...

    Abstract Psychomotor stimulants increase dopamine levels in the striatum and promote locomotion; however, their effects on striatal pathway function in vivo remain unclear. One model that has been proposed to account for these motor effects suggests that stimulants drive hyperactivity via activation and inhibition of direct and indirect pathway striatal neurons, respectively. Although this hypothesis is consistent with the cellular actions of dopamine receptors and received support from optogenetic and chemogenetic studies, it has been rarely tested with in vivo recordings. Here, we test this model and observe that cocaine increases the activity of both pathways in the striatum of awake mice. These changes are linked to a dopamine-dependent cocaine-induced strengthening of upstream orbitofrontal cortex (OFC) inputs to the dorsomedial striatum (DMS) in vivo. Finally, depressing OFC-DMS pathway with a high frequency stimulation protocol in awake mice over-powers the cocaine-induced potentiation of OFC-DMS pathway and attenuates the expression of locomotor sensitization, directly linking OFC-DMS potentiation to cocaine-induced hyperactivity.
    MeSH term(s) Animals ; Behavior, Animal ; Central Nervous System Stimulants/pharmacology ; Cocaine/pharmacology ; Corpus Striatum/drug effects ; Corpus Striatum/metabolism ; Disease Models, Animal ; Dopamine ; Female ; Hyperkinesis/chemically induced ; Hyperkinesis/metabolism ; Locomotion/drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Neurons/drug effects ; Neurons/metabolism ; Optogenetics ; Prefrontal Cortex/drug effects ; Prefrontal Cortex/metabolism
    Chemical Substances Central Nervous System Stimulants ; Cocaine (I5Y540LHVR) ; Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2020-08-10
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-020-17763-8
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  10. Article ; Online: Optogenetically-inspired neuromodulation: Translating basic discoveries into therapeutic strategies.

    Murphy, Caitlin / Matikainen-Ankney, Bridget / Chang, Yu-Hsuan / Copits, Bryan / Creed, Meaghan C

    International review of neurobiology

    2021  Volume 159, Page(s) 187–219

    Abstract: Optogenetic tools allow for the selective activation, inhibition or modulation of genetically-defined neural circuits with incredible temporal precision. Over the past decade, application of these tools in preclinical models of psychiatric disease has ... ...

    Abstract Optogenetic tools allow for the selective activation, inhibition or modulation of genetically-defined neural circuits with incredible temporal precision. Over the past decade, application of these tools in preclinical models of psychiatric disease has advanced our understanding the neural circuit basis of maladaptive behaviors in these disorders. Despite their power as an investigational tool, optogenetics cannot yet be applied in the clinical for the treatment of neurological and psychiatric disorders. To date, deep brain stimulation (DBS) is the only clinical treatment that can be used to achieve circuit-specific neuromodulation in the context of psychiatric. Despite its increasing clinical indications, the mechanisms underlying the therapeutic effects of DBS for psychiatric disorders are poorly understood, which makes optimization difficult. We discuss the variety of optogenetic tools available for preclinical research, and how these tools have been leveraged to reverse-engineer the mechanisms underlying DBS for movement and compulsive disorders. We review studies that have used optogenetics to induce plasticity within defined basal ganglia circuits, to alter neural circuit function and evaluate the corresponding effects on motor and compulsive behaviors. While not immediately applicable to patient populations, the translational power of optogenetics is in inspiring novel DBS protocols by providing a rationale for targeting defined neural circuits to ameliorate specific behavioral symptoms, and by establishing optimal stimulation paradigms that could selectively compensate for pathological synaptic plasticity within these defined neural circuits.
    MeSH term(s) Basal Ganglia/physiology ; Humans ; Mental Disorders/physiopathology ; Mental Disorders/therapy ; Neuronal Plasticity/physiology ; Optogenetics
    Language English
    Publishing date 2021-07-21
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 209876-3
    ISSN 2162-5514 ; 0074-7742
    ISSN (online) 2162-5514
    ISSN 0074-7742
    DOI 10.1016/bs.irn.2021.06.002
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