Erin S Calipari

Erin S Calipari
Vanderbilt University School of Medicine, Nashville TN, USA · Pharmacology

PhD

About

117
Publications
18,083
Reads
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3,667
Citations
Introduction
To learn about the work that my lab does check out our website: www.caliparilab.com One of the most fundamental forms of learning is the ability to associate positive and negative stimuli with cues that predict their occurrence. Dysregulation of these processes can precipitate a number of psychiatric disease states. I seek to characterize the circuits in the brain that underlie both adaptive and maladaptive processes in associative learning.
Additional affiliations
August 2016 - October 2017
Icahn School of Medicine at Mount Sinai
Position
  • Instructor
January 2014 - present
Icahn School of Medicine at Mount Sinai
Position
  • PostDoc Position
August 2009 - September 2013
Wake Forest School of Medicine
Position
  • PhD Student

Publications

Publications (117)
Article
Full-text available
Although both males and females become addicted to cocaine, females transition to addiction faster and experience greater difficulties remaining abstinent. We demonstrate an oestrous cycle-dependent mechanism controlling increased cocaine reward in females. During oestrus, ventral tegmental area (VTA) dopamine neuron activity is enhanced and drives...
Article
Full-text available
The reinforcing and rewarding properties of cocaine are attributed to its ability to increase dopaminergic transmission in nucleus accumbens (NAc). This action reinforces drug taking and seeking and leads to potent and long-lasting associations between the rewarding effects of the drug and the cues associated with its availability. The inability to...
Article
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Dopamine D2 autoreceptors located on the midbrain dopaminergic neurons modulate dopamine (DA) neuron firing, DA release, and DA synthesis through a negative feedback mechanism. Dysfunctional D2 autoreceptors following repeated drug exposure could lead to aberrant DA activity in the ventral tegmental area (VTA) and projection areas such as nucleus a...
Article
Full-text available
Methylphenidate (MPH) is commonly diverted for recreational use, but the neurobiological consequences of exposure to MPH at high, abused doses are not well defined. Here we show that MPH self-administration in rats increases dopamine transporter (DAT) levels and enhances the potency of MPH and amphetamine on dopamine responses and drug-seeking beha...
Article
Full-text available
The dopamine transporter (DAT) is responsible for terminating dopamine (DA) signaling and is the primary site of cocaine's reinforcing actions. Cocaine self-administration has been shown previously to result in changes in cocaine potency at the DAT. To determine whether the DAT changes associated with self-administration are due to differences in i...
Article
Full-text available
Studies investigating the neural mechanisms by which associations between cues and predicted outcomes control behavior often use associative learning frameworks to understand the neural control of behavior. These frameworks do not always account for the full range of effects that novelty can have on behavior and future associative learning. Here, i...
Preprint
Concatenating actions into automatic routines is evolutionarily advantageous as it allows organisms to efficiently use time and energy under predictable conditions. However, over reliance on inflexible behaviors can be life-threatening in a changing environment and can become pathological in disease states such as obsessive compulsive disorder (OCD...
Article
Biological sex has been pinpointed as significant biological factor impacting the prevalence and prognosis of Substance Use Disorder (SUD). Despite the overwhelming utilization of male subjects in SUD research, epidemiological evidence shows that women are the most susceptible population. At the hub of female vulnerability to SUD is significant dys...
Article
Full-text available
At this point in the history of the science of behavior, a focus on neuroscience-based outcomes has become dominant in neuropsychiatric fields at the preclinical and clinical levels of analysis. The notion that behavior is caused by brain function, and that changing brain function can alter behavior, has fueled this push to understand these neurobi...
Preprint
Background The inability to predict when aversive stimuli will and will not occur in is a hallmark of anxiety and stress disorders. Dopamine release in the nucleus accumbens (NAc) is sufficient and necessary for aversive learning and has been linked to both anxiety and stress disorder symptomatology. Thus, understanding how dopamine controls associ...
Article
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Anxiety disorders are complex diseases, and often co-occur with depression. It is as yet unclear if a common neural circuit controls anxiety-related behaviors in both anxiety-alone and comorbid conditions. Here, utilizing the chronic social defeat stress (CSDS) paradigm that induces singular or combined anxiety- and depressive-like phenotypes in mi...
Article
The progressive ratio procedure is used across fields to assess motivation for different reinforcers, define the effects of experimental interventions on motivation, and determine experience‐dependent changes in motivation. However, less is known about how operant training schedules affect performance on this widely utilized task. Here we designed...
Article
Manganese (Mn) is an essential micronutrient but is neurotoxic in excess. Environmental and genetic factors influence vulnerability to Mn toxicity, including sex, age, and the autosomal dominant mutation that causes Huntington disease (HD). To better understand the differential effects of Mn in wild-type (WT) versus YAC128 mice, we examined impacts...
Article
Inhibitory interneurons orchestrate prefrontal cortex (PFC) activity, but we have a limited understanding of the molecular and experience-dependent mechanisms that regulate synaptic plasticity across PFC microcircuits. We discovered that mGlu5 receptor activation facilitates long-term potentiation at synapses from the basolateral amygdala (BLA) ont...
Article
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Cocaine use disorder is associated with alterations in immune function including altered expression of multiple peripheral cytokines in humans—several of which correlate with drug use. Individuals suffering from cocaine use disorder show altered immune system responses to drug-associated cues, highlighting the interaction between the brain and immu...
Article
Background Central histamine (HA) signaling modulates diverse cortical and subcortical circuits throughout the brain, including the nucleus accumbens (NAc). The NAc, a key striatal subregion directing reward-related behavior, expresses diverse HA receptor subtypes that elicit cellular and synaptic plasticity. However, the neuromodulatory capacity o...
Article
A large body of work has aimed to define the precise information encoded by dopaminergic projections innervating the nucleus accumbens (NAc). Prevailing models are based on reward prediction error (RPE) theory, in which dopamine updates associations between rewards and predictive cues by encoding perceived errors between predictions and outcomes. H...
Article
Full-text available
Substance use disorder (SUD) is a chronic neuropsychiatric condition characterized by long-lasting alterations in the neural circuitry regulating reward and motivation. Substantial work has focused on characterizing the molecular substrates that underlie these persistent changes in neural function and behavior. However, this work has overwhelmingly...
Article
Full-text available
Epigenetic mechanisms, like those involving DNA methylation, are thought to mediate the relationship between chronic cocaine dependence and molecular changes in addiction-related neurocircuitry, but have been understudied in human brain. We initially used reduced representation bisulfite sequencing (RRBS) to generate a methylome-wide profile of coc...
Article
With the advent of tools for recording and manipulating activity with high spatiotemporal resolution in defined neural circuits in behaving animals, behavioral neuroscience is now tasked with establishing field-wide standards for implementing and interpreting these powerful approaches. Theoretical frameworks for what constitute proof of fundamental...
Article
Psychostimulant use disorder is a major public health issue, and despite the scope of the problem there are currently no Food and Drug Administration (FDA)-approved treatments. There would be tremendous utility in development of a treatment that could help patients both achieve and maintain abstinence. Previous work from our group has identified gr...
Article
The mesolimbic dopamine system—which originates in the ventral tegmental area and projects to the striatum—has been shown to be involved in the expression of sex-specific behavior and is thought to be a critical mediator of many psychiatric diseases. While substantial work has focused on sex differences in the anatomy of dopamine neurons and relati...
Article
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Microglia, the brain’s resident macrophages, help to regulate brain function by removing dying neurons, pruning non-functional synapses, and producing ligands that support neuronal survival1. Here we show that microglia are also critical modulators of neuronal activity and associated behavioural responses in mice. Microglia respond to neuronal acti...
Article
Dopamine (DA) has important roles in learning, memory, and motivational processes and is highly susceptible to oxidation. In addition to dementia, Alzheimer’s disease (AD) patients frequently exhibit decreased motivation, anhedonia, and sleep disorders, suggesting deficits in dopaminergic neurotransmission. Vitamin C (ascorbate, ASC) is a critical...
Article
Substance use disorder (SUD) is a behavioral disorder characterized by volitional drug consumption. Mouse models of SUD allow for the use of molecular, genetic, and circuit-level tools, providing enormous potential for defining the underlying mechanisms of this disorder. However, the relevance of results depends on the validity of the mouse models...
Article
Full-text available
MiR-124 is a highly expressed miRNA in the brain and regulates genes involved in neuronal function. We report that miR-124 post-transcriptionally regulates PARP-1. We have identified a highly conserved binding site of miR-124 in the 3′-untranslated region (3′UTR) of Parp-1 mRNA. We demonstrate that miR-124 directly binds to the Parp-1 3′UTR and mut...
Article
Alcohol use disorder (AUD) places a tremendous burden on society, with approximately two billion alcohol users in the world. While most people drink alcohol recreationally, a subpopulation (3–5%) engages in reckless and compulsive drinking, leading to the development of AUD and alcohol dependence. The Ventral Tegmental Area (VTA)-Nucleus Accumbens...
Article
Full-text available
Heightened aggression is characteristic of multiple neuropsychiatric disorders and can have various negative effects on patients, their families and the public. Recent studies in humans and animals have implicated brain reward circuits in aggression and suggest that, in subsets of aggressive individuals, domination of subordinate social targets is...
Article
A large body of work has focused on understanding stimulus-driven behavior, sex differences in these processes, and the neural circuits underlying them. Many preclinical mouse models present rewarding or aversive stimuli in isolation, ignoring that ethologically, reward seeking requires the consideration of potential aversive outcomes. In addition,...
Article
Full-text available
Vulnerability to relapse during periods of attempted abstinence from cocaine use is hypothesized to result from the rewiring of brain reward circuitries, particularly ventral tegmental area (VTA) dopamine neurons. How cocaine exposures act on midbrain dopamine neurons to precipitate addiction-relevant changes in gene expression is unclear. We found...
Article
Depression is a common disorder that affects women at twice the rate of men. Here, we report that long non-coding RNAs (lncRNAs), a recently discovered class of regulatory transcripts, represent about one-third of the differentially expressed genes in the brains of depressed humans and display complex region- and sex-specific patterns of regulation...
Article
Full-text available
Regulation of axonal dopamine release by local microcircuitry is at the hub of several biological processes that govern the timing and magnitude of signaling events in reward‐related brain regions. An important characteristic of dopamine release from axon terminals in the striatum is that it is rapidly modulated by local regulatory mechanisms. Thes...
Preprint
Full-text available
Background: Psychostimulant use disorder is a major public health issue, and despite the scope of the problem there are currently no FDA approved treatments. There would be tremendous utility in development of a treatment that could help patients both achieve and maintain abstinence. Previous work from our group has identified granulocyte-colony st...
Preprint
Full-text available
Heightened aggression is characteristic of multiple neuropsychiatric disorders and can have a wide variety of negative effects on patients, their families, and the public. Recent studies in humans and animals have implicated brain reward circuits in aggression and suggest that, in subsets of aggressive individuals, repeated domination of subordinat...
Article
Substance use disorder (SUD) is a behavioral disorder characterized by cycles of abstinence, drug seeking, and relapse. SUD is characterized by aberrant learning processes which develop after repeated exposure to drugs of abuse. At the core of this phenotype is the persistence of symptoms, such as craving and relapse to drug seeking, long after the...
Preprint
Substance use disorder is a behavioral disorder characterized by volitional drug consumption, compulsive behavior, drug seeking, and relapse. Mouse models of substance use disorder allow for the use of molecular, genetic, and circuit level tools, which provide enormous potential for defining the underlying mechanisms of this disorder. However, the...
Article
Addiction to psychostimulants is a major public health crisis and currently there are no FDA-approved pharmacotherapies. Development of widely effective treatments is hindered because the mechanisms underlying sex differences in the response to cocaine are poorly understood. Recently, we identified the neuroactive cytokine granulocyte-colony stimul...
Preprint
Full-text available
Background: Sex is a critical biological variable in the neuropathology of psychiatric disease, and in many cases, women represent a vulnerable population. It has been hypothesized that sex differences in neuropsychiatric disorders are manifestations of differences in basic reward processing. However, preclinical models often present rewards in iso...
Article
GPR83, the receptor for the neuropeptide PEN, exhibits high expression in the nucleus accumbens of the human and rodent brain, suggesting that it plays a role in modulating the mesolimbic reward pathway. However, the cell-type specific expression of GPR83, its functional impact in the reward pathway, and in drug reward-learning has not been fully e...
Article
Addictive behaviors, including relapse, are thought to depend in part on long-lasting drug-induced adaptations in dendritic spine signaling and morphology in the nucleus accumbens (NAc). While the influence of activity-dependent actin remodeling in these phenomena has been studied extensively, the role of microtubules and associated proteins remain...
Article
While preclinical work has aimed to outline the neural mechanisms of drug addiction, it has overwhelmingly focused on male subjects. There has been a push in recent years to incorporate females into existing addiction models; however, males and females often have different behavioral strategies, making it important to not only include females, but...
Preprint
Full-text available
Drugs of abuse are known to alter activity in areas of brain associated with reward, cognition and decision making. Changes in neural activity in these regions that follow repeated exposures to abused substances may underlie the development of addictive behaviors and contribute to the high rates of relapse associated with drug use. Measuring real-t...
Article
Drug addiction is a major public health concern across the world for which there are limited treatment options. In order to develop new therapies to correct the behavioral deficits that result from repeated drug use, we need to understand the neural circuit dysfunction that underlies the pathophysiology of the disorder. Because the initial reinforc...
Article
A fundamental aspect of survival is the ability to refine behaviors based on internal and external contexts. Interpretation of rewarding stimuli is driven by integration of a diverse number of inputs including contextual cues, hormone levels, and perceived valence of potentially stressful stimuli. These factors can influence the way that an organis...
Article
Full-text available
Cocaine addiction is characterized by aberrant plasticity of the mesolimbic dopamine circuit, leading to dysregulation of motivation to seek and take drug. Despite the significant toll that cocaine use disorder exacts on society, there are currently no available pharmacotherapies. We have recently identified granulocyte-colony stimulating factor (G...
Article
Background: Homeostatic plasticity in mesolimbic dopamine (DA) neurons plays an essential role in mediating resilience to social stress. Recent evidence implicates an association between stress resilience and projections from the locus coeruleus (LC) to the ventral tegmental area (VTA) (LC→VTA) DA system. However, the precise circuitry and molecul...
Article
Full-text available
Deficits in motivation and cognition are hallmark symptoms of multiple psychiatric diseases. These symptoms are disruptive to quality of life and often do not improve with available medications. In recent years there has been increased interest in the role of the immune system in neuropsychiatric illness, but to date no immune-related treatment str...
Article
Full-text available
The role of somatostatin interneurons in nucleus accumbens (NAc), a key brain reward region, remains poorly understood due to the fact that these cells account for < 1% of NAc neurons. Here, we use optogenetics, electrophysiology, and RNA-sequencing to characterize the transcriptome and functioning of NAc somatostatin interneurons after repeated ex...
Article
Background Global changes in gene expression underlying circuit and behavioral dysregulation associated with cocaine addiction remain incompletely understood. Here, we show how a history of cocaine self-administration (SA) “re-programs” transcriptome-wide responses throughout the brain’s reward circuitry at baseline and in response to context and/o...
Article
Full-text available
The original version of this Article contained an error in the spelling of the author Scott Edwards, which was incorrectly given as Scott Edward. This has now been corrected in both the PDF and HTML versions of the Article.
Article
Full-text available
Cocaine addiction is characterized by dysfunction in reward-related brain circuits, leading to maladaptive motivation to seek and take the drug. There are currently no clinically available pharmacotherapies to treat cocaine addiction. Through a broad screen of innate immune mediators, we identify granulocyte-colony stimulating factor (G-CSF) as a p...