Elyssa B. Margolis
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View article: Author response: Chronic hyperactivation of midbrain dopamine neurons causes preferential dopamine neuron degeneration
Author response: Chronic hyperactivation of midbrain dopamine neurons causes preferential dopamine neuron degeneration Open
View article: Chronic hyperactivation of midbrain dopamine neurons causes preferential dopamine neuron degeneration
Chronic hyperactivation of midbrain dopamine neurons causes preferential dopamine neuron degeneration Open
Parkinson’s disease (PD) is characterized by the death of substantia nigra pars compacta (SNc) dopamine (DA) neurons, but the pathophysiological mechanisms that precede and drive their death remain unknown. The activity of DA neurons is li…
View article: Chronic hyperactivation of midbrain dopamine neurons causes preferential dopamine neuron degeneration
Chronic hyperactivation of midbrain dopamine neurons causes preferential dopamine neuron degeneration Open
Parkinson’s disease (PD) is characterized by the death of substantia nigra (SNc) dopamine (DA) neurons, but the pathophysiological mechanisms that precede and drive their death remain unknown. The activity of DA neurons is likely altered i…
View article: Author response: Chronic hyperactivation of midbrain dopamine neurons causes preferential dopamine neuron degeneration
Author response: Chronic hyperactivation of midbrain dopamine neurons causes preferential dopamine neuron degeneration Open
View article: Structure-guided design of partial agonists at an opioid receptor
Structure-guided design of partial agonists at an opioid receptor Open
Chronic pain and opioid overdose deaths highlight the need for non-addictive analgesics with novel mechanisms. The δ opioid receptor (δOR) is a promising target, as it lacks the respiratory depression associated with µ opioid receptor (µOR…
View article: CHCHD2 mutant mice display mitochondrial protein accumulation and disrupted energy metabolism
CHCHD2 mutant mice display mitochondrial protein accumulation and disrupted energy metabolism Open
Mutations in the mitochondrial cristae protein CHCHD2 lead to a late-onset autosomal dominant form of Parkinson’s disease (PD) which closely resembles idiopathic PD, providing the opportunity to gain new insights into the mechanisms of mit…
View article: Author response: Chronic hyperactivation of midbrain dopamine neurons causes preferential dopamine neuron degeneration
Author response: Chronic hyperactivation of midbrain dopamine neurons causes preferential dopamine neuron degeneration Open
Parkinson's disease (PD) is characterized by the death of substantia nigra (SNc) dopamine (DA) neurons, but the pathophysiological mechanisms that precede and drive their death remain unknown. The activity of DA neurons is likely altered i…
View article: Chronic hyperactivation of midbrain dopamine neurons causes preferential dopamine neuron degeneration
Chronic hyperactivation of midbrain dopamine neurons causes preferential dopamine neuron degeneration Open
Parkinson’s disease (PD) is characterized by the death of substantia nigra (SNc) dopamine (DA) neurons, but the pathophysiological mechanisms that precede and drive their death remain unknown. The activity of DA neurons is likely altered i…
View article: Chronic hyperactivation of midbrain dopamine neurons causes preferential dopamine neuron degeneration
Chronic hyperactivation of midbrain dopamine neurons causes preferential dopamine neuron degeneration Open
Parkinson’s disease (PD) is characterized by the death of substantia nigra pars compacta (SNc) dopamine (DA) neurons, but the pathophysiological mechanisms that precede and drive their death remain unknown. The activity of DA neurons is li…
View article: Structure-Guided Design of Partial Agonists at an Opioid Receptor
Structure-Guided Design of Partial Agonists at an Opioid Receptor Open
The persistence of chronic pain and continuing overdose deaths from pain-relieving opioids targeting µ opioid receptor (µOR) have fueled the need for reliable long-term analgesics which use different targets and mechanisms. The δ opioid re…
View article: Chronic hyperactivation of midbrain dopamine neurons causes preferential dopamine neuron degeneration
Chronic hyperactivation of midbrain dopamine neurons causes preferential dopamine neuron degeneration Open
Parkinson’s disease (PD) is characterized by the death of substantia nigra (SNc) dopamine (DA) neurons, but the pathophysiological mechanisms that precede and drive their death remain unknown. The activity of DA neurons is likely altered i…
View article: The life and times of endogenous opioid peptides: Updated understanding of synthesis, spatiotemporal dynamics, and the clinical impact in alcohol use disorder
The life and times of endogenous opioid peptides: Updated understanding of synthesis, spatiotemporal dynamics, and the clinical impact in alcohol use disorder Open
View article: A diencephalic circuit in rats for opioid analgesia but not positive reinforcement
A diencephalic circuit in rats for opioid analgesia but not positive reinforcement Open
Mu opioid receptor (MOR) agonists are potent analgesics, but also cause sedation, respiratory depression, and addiction risk. The epithalamic lateral habenula (LHb) signals aversive states including pain, and here we found that it is a pot…
View article: A Novel Mitragynine Analog with Low-Efficacy Mu Opioid Receptor Agonism Displays Antinociception with Attenuated Adverse Effects
A Novel Mitragynine Analog with Low-Efficacy Mu Opioid Receptor Agonism Displays Antinociception with Attenuated Adverse Effects Open
Mitragynine and 7-hydroxymitragynine (7OH) are the major alkaloids mediating the biological actions of the psychoactive plant kratom. To investigate the structure-activity relationships of mitragynine/7OH templates, we diversified the arom…
View article: A novel mitragynine analog with low efficacy mu-opioid receptor agonism displays antinociception with attenuated adverse effects
A novel mitragynine analog with low efficacy mu-opioid receptor agonism displays antinociception with attenuated adverse effects Open
Dried kratom leaves are anecdotally used for the treatment of pain, opioid dependence, and alcohol use disorder. We have previously shown that kratom’s natural products (mitragynine) and semi-synthetic analogs (7-hydroxy mitragynine (7OH) …
View article: Ventral tegmental area GABA, glutamate, and glutamate‐GABA neurons are heterogeneous in their electrophysiological and pharmacological properties
Ventral tegmental area GABA, glutamate, and glutamate‐GABA neurons are heterogeneous in their electrophysiological and pharmacological properties Open
The ventral tegmental area (VTA) contains dopamine neurons intermixed with GABA‐releasing (expressing vesicular GABA transporter, VGaT), glutamate‐releasing (expressing vesicular glutamate transporter 2, VGluT2), and glutamate‐GABA co‐rele…
View article: Author response for "Ventral Tegmental Area GABA, glutamate, and glutamate‐GABA neurons are heterogeneous in their electrophysiological and pharmacological properties"
Author response for "Ventral Tegmental Area GABA, glutamate, and glutamate‐GABA neurons are heterogeneous in their electrophysiological and pharmacological properties" Open
View article: A diencephalic circuit for opioid analgesia but not positive reinforcement
A diencephalic circuit for opioid analgesia but not positive reinforcement Open
Mu opioid receptor (MOR) agonists are the most effective analgesics, but their use risks respiratory depression and addiction. The epithalamic lateral habenula (LHb) is a critical site that signals aversive states, often via indirect inhib…
View article: Differential effects of novel kappa opioid receptor antagonists on dopamine neurons using acute brain slice electrophysiology
Differential effects of novel kappa opioid receptor antagonists on dopamine neurons using acute brain slice electrophysiology Open
Activation of the kappa opioid receptor (KOR) contributes to the aversive properties of stress, and modulates key neuronal circuits underlying many neurobehavioral disorders. KOR agonists directly inhibit ventral tegmental area (VTA) dopam…
View article: A diencephalic circuit for opioid analgesia but not positive reinforcement
A diencephalic circuit for opioid analgesia but not positive reinforcement Open
Mu opioid receptor (MOR) agonists are potent analgesics, but also cause sedation, respiratory depression, and addiction risk. The epithalamic lateral habenula (LHb) signals aversive states including pain and we found it is a potent site fo…
View article: Differential Modulation of Ventral Tegmental Area Circuits by the Nociceptin/Orphanin FQ System
Differential Modulation of Ventral Tegmental Area Circuits by the Nociceptin/Orphanin FQ System Open
The neuropeptide nociceptin/orphanin FQ (N/OFQ) can be released by stressors and is associated with disorders of emotion regulation and reward processing. N/OFQ and its receptor, NOP, are enriched in dopaminergic pathways, and intra-ventri…
View article: Five Decades of Research on Opioid Peptides: Current Knowledge and Unanswered Questions
Five Decades of Research on Opioid Peptides: Current Knowledge and Unanswered Questions Open
View article: Biased signaling by endogenous opioid peptides
Biased signaling by endogenous opioid peptides Open
Significance There are >20 different endogenous opioid peptides derived from the three precursors proopiomelanocortin, proenkephalin, and prodynorphin; a long-standing question is the biological utility of having this variety of peptides. …
View article: Differential effects of novel kappa opioid receptor antagonists on dopamine neurons using acute brain slice electrophysiology
Differential effects of novel kappa opioid receptor antagonists on dopamine neurons using acute brain slice electrophysiology Open
Activation of the kappa opioid receptor (KOR) contributes to the aversive properties of stress, and modulates key neuronal circuits underlying many neurobehavioral disorders. KOR agonists directly inhibit ventral tegmental area (VTA) dopam…
View article: Differential modulation of ventral tegmental area circuits by the nociceptin/orphanin FQ system
Differential modulation of ventral tegmental area circuits by the nociceptin/orphanin FQ system Open
The neuropeptide nociceptin/orphanin FQ (N/OFQ) can be released by stressors and is associated with disorders of emotion regulation and reward processing. N/OFQ and its receptor, NOP, are enriched in dopaminergic pathways, and intra-ventri…
View article: A Midbrain Circuit that Mediates Headache Aversiveness in Rats
A Midbrain Circuit that Mediates Headache Aversiveness in Rats Open
View article: A midbrain circuit that mediates headache aversiveness
A midbrain circuit that mediates headache aversiveness Open
These data demonstrate a direct connection between the ventrolateral periaqueductal gray (vlPAG) and the ventral tegmental area (VTA) that contributes to headache aversiveness. Many VTA neurons receive monosynaptic input from the vlPAG, an…
View article: Dopaminergic cellular and circuit contributions to kappa opioid receptor mediated aversion
Dopaminergic cellular and circuit contributions to kappa opioid receptor mediated aversion Open
View article: Dopaminergic Cellular and Circuit Contributions to Kappa Opioid Receptor Mediated Aversion
Dopaminergic Cellular and Circuit Contributions to Kappa Opioid Receptor Mediated Aversion Open
Neural circuits that enable an organism to protect itself by promoting escape from immediate threat and avoidance of future injury are conceptualized to carry an “aversive” signal. One of the key molecular elements of these cir…
View article: Dopamine neurons create Pavlovian conditioned stimuli with circuit-defined motivational properties
Dopamine neurons create Pavlovian conditioned stimuli with circuit-defined motivational properties Open