Publications by authors named "Melissa Herman"

Introduction: The increasing prevalence of electronic nicotine delivery systems and alcohol drinking has led to increases in nicotine and alcohol co-use. However, the impact of ENDs on brain activity and binge drinking behavior is not fully understood.

Aims And Methods: We subjected female and male C57BL/6J mice to a voluntary drinking and electronic nicotine vapor exposure paradigm.

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Food deprivation is used in many experimental models and is becoming increasingly prevalent in human diets. The impact of food deprivation on specific brain regions, including the nucleus of the tractus solitarius (NTS), a region that is involved in hunger and satiety sensing, remains to be determined. The NTS is a heterogeneous nucleus that includes corticotropin releasing factor receptor 1 (CRF1) neurons.

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Article Synopsis
  • The release of neurotransmitters at synapses relies on a series of protein interactions, particularly involving complexins, which play a role in regulating synaptic transmission.
  • Research on the N-terminus of complexin II, focusing on its hydrophobic amino acids, shows that preserving this property supports its stimulatory function, while changes disrupt neurotransmitter release.
  • Specific mutations in the N-terminus, particularly residue changes, can enhance spontaneous release but negatively affect evoked release, highlighting the importance of precise amino acid composition in managing synaptic neurotransmitter dynamics.
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Frequent use of pain relief medications among patients with migraine can result in disease worsening and medication-overuse headache (MOH), a painful and debilitating condition. We sought to conduct a cross-sectional survey among adult patients diagnosed with migraine to determine: 1) their awareness of MOH, and 2) their knowledge of the condition and its prevention, and 3) the association of these factors with actual use of pain relief medications. We recruited and interviewed 200 English-speaking adults with migraine who had a clinic visit with a neurologist or primary care provider within the past month.

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Psychedelics have experienced renewed interest following positive clinical effects, however the neurobiological mechanisms underlying effects remain unclear. The paraventricular nucleus of the hypothalamus (PVN) plays an integral role in stress response, autonomic function, social behavior, and other affective processes. We investigated the effect of psilocin, the psychoactive metabolite of psilocybin, on PVN reactivity in Sprague Dawley rats.

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Alcohol use disorder (AUD) is a major public health concern that despite its prevalence, lacks a widely-effective treatment due to the complexity of AUD pathology. AUD is highly comorbid with other psychiatric conditions including anxiety and mood disorders, however it is unclear how these disorders influence each other. The underlying etiology of these comorbidities is difficult to decipher and factors including sex, stress, and the environment further complicate both diagnosis and treatment strategies.

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Objectives: Medication overuse headache (MOH) is a common, debilitating condition occurring when migraine patients overuse pain relief medications. We conducted a convergent mixed methods study examining patient-provider communication on MOH.

Methods: Migraine patients were identified from one academic health center via electronic health records.

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Article Synopsis
  • - The study investigates the role of complexin II (Cpx) in regulating neurotransmitter release at central synapses, focusing specifically on its N-terminal region (amino acids 1-27) which plays a critical role in both stimulating and inhibiting synaptic transmission.
  • - Through experiments such as mutagenesis and membrane fusion assays, the research reveals that the hydrophobic characteristics of the N-terminus are important for enhancing spontaneous neurotransmitter release, while alterations in specific amino acids can impair evoked release and affect the release pool size.
  • - The findings highlight the nuanced functions of Cpx in synaptic activity, emphasizing its effect on the balance between spontaneous and evoked neurotransmitter release in mouse hippocampal neurons.
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  • - Psychedelic drugs like LSD and psilocybin show promise as treatments for various mental health issues, including depression and PTSD, by activating specific brain receptors (HTR2A).
  • - Researchers developed engineered mice to help map and study HTR2A receptors and the neurons that express them, allowing for a clearer understanding of how these psychedelics work in the brain.
  • - Behavioral experiments confirmed that psychedelics affect these mice as expected, and further electrical activity studies showed how a neurotransmitter (5-HT) impacts neuron firing, paving the way for deeper insights into the effects of psychedelics.
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The central nucleus of the amygdala (CeA) is implicated in alcohol use disorder (AUD) and AUD-associated plasticity. The CeA is a primarily GABAergic nucleus that is subdivided into lateral and medial compartments with genetically diverse subpopulations. GABA receptors are heteromeric pentamers with subunits conferring distinct physiological characteristics.

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In 2021, 131 million adult Americans reported drinking alcohol in the last month, despite the well-known consequences of alcohol consumption. While alcohol use disorders (AUDs) are associated with both mood and chronic pain disorders, the relationship between alcohol drinking and affective and nociceptive behaviors remains unclear. Corticotropin releasing factor receptor-1 (CRF1) has been implicated in alcohol drinking, affective states, and pain sensitivity, often in a sex-dependent manner.

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The use of Electronic Nicotine Delivery Systems (ENDS) is increasing in prevalence and popularity. ENDS are a rapidly evolving technology as devices and e-liquid formulations adapt to policy restrictions and market demand To identify the impacts of nicotine formulation and concentration, we exposed female and male C57BL/6J mice to passive electronic vaporization of different nicotine formulations (freebase or salt) and concentrations (1% or 3%) and measured serum nicotine metabolite levels, brain activity by cFos expression, and anxiety-like and motivated behavior using the novelty suppressed feeding test. We found that the 3% freebase nicotine vapor group displayed significantly higher serum nicotine levels than either 1% or 3% nicotine salt formulations, and female mice displayed higher serum nicotine and cotinine levels compared to males.

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Article Synopsis
  • The study investigates how nicotine affects corticotropin-releasing factor receptor 1 (CRF1) neurons in the ventral tegmental area (VTA) of male and female mice, focusing on their roles in addiction and stress response.
  • It finds that CRF1 neurons, mainly dopaminergic, show distinct responses to nicotine based on sex, with females exhibiting higher firing rates and altered inhibitory signaling compared to males.
  • Chronic nicotine exposure leads to reduced basal phasic inhibition in both sexes, eliminating sex differences in response to nicotine, and suggests that these changes may influence behaviors related to addiction and stress.
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The central nucleus of the amygdala (CeA) is a critical brain region in the integration of emotional behaviors and is one of the major output areas of the amygdaloid complex. The CeA is composed of GABAergic interneurons and projection neurons which co-express a range of peptides including neuropeptide Y (NPY). Importantly, GABA and NPY signaling, via the NPY Y1 receptor (Y1R), in the CeA modulate binge-like ethanol intake in rodents and these systems undergo neuroplastic alterations following a history of ethanol consumption.

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Corticotropin-releasing factor type-1 (CRF) receptors are critical to stress responses because they allow neurons to respond to CRF released in response to stress. Our understanding of the role of CRF-expressing neurons in CRF-mediated behaviors has been largely limited to mouse experiments due to the lack of genetic tools available to selectively visualize and manipulate CRF cells in rats. Here, we describe the generation and validation of a transgenic CRF-Cre-Tomato rat.

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Corticotropin-releasing factor (CRF) signaling in the central nucleus of the amygdala (CeA) plays a critical role in rodent models of excessive alcohol drinking. However, the source of CRF acting in the CeA during alcohol withdrawal remains to be identified. In the present study, we hypothesized that CeA CRF interneurons may represent a behaviorally relevant source of CRF to the CeA increasing motivation for alcohol via negative reinforcement.

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Alcohol is a commonly used drug that can produce alcohol use disorders (AUDs). Few individuals with AUDs receive treatment and treatment options are complicated by issues with effectiveness and compliance. Alcohol has been shown to differentially affect specific brain regions and an improved understanding of circuit-specific dysregulation caused by alcohol is warranted.

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A major barrier to remission from an alcohol use disorder (AUD) is the continued risk of relapse during abstinence. Assessing the neuroadaptations after chronic alcohol and repeated abstinence is important to identify mechanisms that may contribute to relapse. In this study, we used a rhesus macaque model of long-term alcohol use and repeated abstinence, providing a platform to extend mechanistic findings from rodents to primates.

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Plasticity in the dentate gyrus (DG) is strongly influenced by ethanol, and ethanol experience alters long-term memory consolidation dependent on the DG. However, it is unclear if DG plasticity plays a role in dysregulation of long-term memory consolidation during abstinence from chronic ethanol experience. Outbred male Wistar rats experienced 7 weeks of chronic intermittent ethanol vapor exposure (CIE).

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Article Synopsis
  • Resting-state fMRI has advanced our understanding of brain networks through new databases in the rodent research community, though establishing standardization is hampered by the common use of anisotropic EPI imaging methods.
  • The authors proposed a high-resolution isotropic EPI protocol for the rat brain that provides comprehensive brain coverage and better data accuracy in comparison to existing methods.
  • Utilizing their new protocol, the researchers collected data from 87 rats and developed an EPI template for improved brain mapping, which facilitated identification of intrinsic brain activity patterns and spatially-defined functional regions of interest.
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  • The study found that while CRF1 antagonists show promise in preclinical settings for reducing alcohol consumption, clinical trials have not produced similar results in humans with alcohol use disorder (AUD).
  • Confounding factors include differences in study design, such as the use of experimenter-administered alcohol and a lack of female subject representation, which may limit the applicability of preclinical findings.
  • The research revealed that chronic voluntary alcohol drinking led to changes in CRF1+ neurons that affected how these neurons respond to alcohol, with noticeable differences in response between male and female mice, suggesting potential reasons for the different efficacy of CRF1 antagonists in treating AUD in women.
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Long-term alcohol use results in behavioral deficits including impaired working memory, elevated anxiety, and blunted inhibitory control that is associated with prefrontal cortical (PFC) dysfunction. Preclinical observations demonstrate multiple impairments in GABAergic neurotransmission onto deep-layer principal cells (PCs) in the prelimbic cortex that suggest dependence-related cortical dysfunction is the product of elevated excitability in these cells. Despite accumulating evidence showing alcohol-induced changes in interneuron signaling onto PCs differ between sexes, there is limited data explicitly evaluating sex-specific ethanol effects on excitatory signaling onto deep-layer PCs that may further contribute to deficits in PFC-dependent behaviors.

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Efficient neurotransmitter release at the presynaptic terminal requires docking of synaptic vesicles to the active zone membrane and formation of fusion-competent synaptic vesicles near voltage-gated Ca channels. Rab3-interacting molecule (RIM) is a critical active zone organizer, as it recruits Ca channels and activates synaptic vesicle docking and priming via Munc13-1. However, our knowledge about Munc13-independent contributions of RIM to active zone functions is limited.

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The central amygdala (CeA) is a critical regulator of emotional behavior that has been implicated in psychiatric illnesses, including anxiety disorders and addiction. The CeA corticotropin releasing factor receptor 1 (CRF1) system has been implicated in alcohol use disorder (AUD) and mood disorders, and has been shown to regulate anxiety-like behavior and alcohol consumption in rodents. However, the effects of CRF signaling within the CRF receptor 1-containing (CRF1+) population of the CeA remain unclear, and the effects of ethanol and CRF1 manipulations in female rodents have not been assessed.

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Tobacco smoking is highly addictive and causes respiratory disease, cardiovascular disease and multiple types of cancer. Electronic-cigarettes (e-cigarettes) are non-combustible tobacco alternatives that aerosolize nicotine and flavouring agents in a propylene glycol-vegetable glycerine vehicle. They were originally envisaged as a tobacco cessation aid, but whether or not they help people to quit tobacco use is controversial.

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