Alexxai V Kravitz

Alexxai V Kravitz
Washington University in St. Louis | WUSTL , Wash U · Department of Psychiatry

PhD

About

92
Publications
23,028
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
4,767
Citations
Introduction
Dr. Kravitz obtained his PhD in Neuroscience from the University of Pennsylvania in 2009 and subsequently completed a postdoc at the Gladstone Institutes in San Francisco, CA. Dr. Kravitz joined the NIDDK in December of 2012. His research focuses on understanding reward circuitry in the brain, and how dysfunction in this circuitry contributes to obesity. The lab uses a variety of approaches to examine this, including behavioral testing, in vivo electrophysiology, and optogenetics

Publications

Publications (92)
Preprint
Full-text available
The central nucleus of the amygdala (CeA) is involved in the expression of fear and has been implicated in several anxiety disorders. Anatomically, it is divided in a medial (CeM), a lateral (CeL) and a capsular division (CeC). The CeA is densely innervated by dopaminergic projections that originate in the ventral periaqueductal gray/dorsal raphe (...
Preprint
Threat-response neural circuits are conserved across species and have roles in normal behaviors and psychiatric diseases. Maladaptive changes in these neural circuits contribute to stress, mood, and anxiety disorders. Active coping in response to stressors is psychosocial factor associated with resilience against stress induced mood and anxiety dis...
Article
Full-text available
Fiber photometry enables recording of population neuronal calcium dynamics in awake mice. While the popularity of fiber photometry has grown in recent years, it remains unclear whether photometry reflects changes in action potential firing (that is, ‘spiking’) or other changes in neuronal calcium. In microscope-based calcium imaging, optical and an...
Article
Recent data demonstrate that noradrenergic neurons of the locus coeruleus (LC-NE) are required for fear-induced suppression of feeding, but the role of endogenous LC-NE activity in natural, homeostatic feeding remains unclear. Here, we found that LC-NE activity was suppressed during food consumption, and the magnitude of this neural response was at...
Article
Background A greater understanding of how the brain controls appetite is fundamental to develop new approaches to treat disease characterized by dysfunctional feeding behavior, such as obesity and anorexia nervosa. Methods By modeling neural network dynamics related to homeostatic state and BMI, we identified a novel pathway projecting from the me...
Article
Full-text available
The use of rodents to acquire understanding of the function of neural circuits and of the physiological, genetic and developmental underpinnings of behaviour has been constrained by limitations in the scalability, automation and high-throughput operation of implanted wireless neural devices. Here we report scalable and modular hardware and software...
Article
Oxycodone is one of the most commonly prescribed analgesics for moderate to severe pain disorders. While effective in the short term, long-term use can result in a myriad of unwanted side-effects which include tolerance, physical dependence and the development of opioid use disorder. Δ9-Tetrahydrocannabinol (Δ9-THC), is a partial cannabinoid recept...
Preprint
Full-text available
Obesity is a chronic relapsing disorder that is caused by an excess of caloric intake relative to energy expenditure. In addition to homeostatic feeding mechanisms, there is growing recognition of the involvement of food reward and motivation in the development of obesity. However, it remains unclear how brain circuits that control food reward and...
Article
Full-text available
Agouti-related peptide (AgRP) neurons increase motivation for food, however whether metabolic sensing of homeostatic state in AgRP neurons potentiates motivation by interacting with dopamine reward systems is unexplored. As a model of impaired metabolic-sensing, we used the AgRP-specific deletion of carnitine acetyltransferase ( Crat ) in mice. We...
Article
Full-text available
Feeding is critical for survival and disruption in the mechanisms that govern food intake underlie disorders such as obesity and anorexia nervosa. It is important to understand both food intake and food motivation to reveal mechanisms underlying feeding disorders. Operant behavioral testing can be used to measure the motivational component to feedi...
Preprint
Full-text available
Prescription opioid use is an initiating factor driving the current opioid epidemic. There are several challenges with modeling prescription opioid addiction. First, prescription opioids such as oxycodone are orally self-administered and have different pharmacokinetics and dynamics than morphine or fentanyl. This oral route of administration determ...
Preprint
Full-text available
Calcium recording via fiber photometry is commonly used as a proxy for recording population neuronal activity in vivo, yet the biological source of the photometry signal remains unclear. Here, using simultaneous in vivo extracellular electrophysiology and fiber photometry in the striatum, along with endoscopic 1-photon and 2-photon calcium imaging,...
Preprint
Full-text available
Feeding is critical for survival and disruption in the mechanisms that govern food intake underlie disorders such as obesity and anorexia nervosa. It is important to understand both food intake and food motivation to reveal mechanisms underlying feeding disorders. Operant behavioral testing can be used to measure the motivational component to feedi...
Article
Full-text available
Marked deficits in glucose availability, or glucoprivation, elicit organism-wide counter-regulatory responses whose purpose is to restore glucose homeostasis. However, while catecholamine neurons of the ventrolateral medulla (VLMCA) are thought to orchestrate these responses, the circuit and cellular mechanisms underlying specific counter-regulator...
Article
The dorsal striatum is important for motor control. Yet whether that control encompasses procedural memories, kinematic refinement, or both is still debated. A recent study has shed new light on the role of the dorsal striatum in learned movement sequences and the effort required to refine them.
Article
Full-text available
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 neu...
Article
Full-text available
Striatal dopamine D2 receptors (D2Rs) are important for motor output. Selective deletion of D2Rs from indirect pathway-projecting medium spiny neurons (iMSNs) impairs locomotor activities in a task-specific manner. However, the role of D2Rs in the initiation of motor actions in reward seeking and taking is not fully understood, and there is little...
Article
Full-text available
Recurring and excessive violence and aggression are serious concerns for the individual and society at large and is a symptom of many psychiatric illnesses such as PTSD. The circuit and synaptic mechanisms underlying experience-induced aggression escalation, however, are poorly understood. Here we find that prior attack experience leading to an inc...
Article
Full-text available
Natural genetic variants of Neuregulin1 (NRG1) and its cognate receptor ErbB4 are associated with a risk for schizophrenia. Whereas most studies on NRG1-ErbB4 signaling have focused on GABAergic interneurons, ErbB4 is also expressed by midbrain dopaminergic neurons where it modulates extracellular dopamine (DA) levels. Here, we report that extracel...
Article
Full-text available
Video tracking is an essential tool in rodent research. Here, we demonstrate a machine vision rodent tracking camera based on a low-cost, open-source, machine vision camera, the OpenMV Cam M7. We call our device the rodent arena tracker (RAT), and it is a pocket-sized machine vision-based position tracker. The RAT does not require a tethered comput...
Article
Full-text available
Objective: While changes in diet often result in short-term weight loss, weight loss is not typically maintained. It remains unclear why long-term weight loss is so difficult. It was hypothesized that obesity produces persistent changes in behavior that bias animals toward weight regain after weight loss. Methods: Mice were induced to gain weigh...
Article
Full-text available
The dorsal striatum has been linked to decision-making under conflict, but the mechanism by which striatal neurons contribute to approach-avoidance conflicts remains unclear. We hypothesized that striatopallidal dopamine D2 receptor (D2R)-expressing neurons promote avoidance, and tested this hypothesis in two exploratory approach-avoidance conflict...
Article
Full-text available
A correction to this paper has been published and can be accessed via a link at the top of the paper.
Article
Full-text available
The striatum is critical for controlling motor output. However, it remains unclear how striatal output neurons encode and facilitate movement. A prominent theory suggests that striatal units encode movements in bursts of activity near specific events, such as the start or end of actions. These bursts are theorized to gate or permit specific motor a...
Preprint
Full-text available
Noradrenergic neurons of the locus coeruleus (LC-NE) are known to play an important role in arousal, emotion, memory and cognition. In the present study, we use fiber photometry combined with chemogenetic and optogenetic approaches to demonstrate a previously unrecognized role for LC-NE neurons in the modulation of feeding. We show that endogenous...
Preprint
Full-text available
Stimulants are one of the most widely prescribed classes of pharmaceuticals, but it is unclear which brain pathways underlie their therapeutic and adverse actions. Here, with real-time monitoring of circuit plasticity, we demonstrate that psychostimulants strengthen orbitofrontal (OFC) to dorsomedial striatum (DMS) pathway synapses, and increase st...
Article
Full-text available
Measuring ingestive behavior of liquids in rodents is commonly used in studies of reward, metabolism, and circadian biology. Common approaches for measuring liquid intake in real time include computer-tethered lickometers or video-based systems. Additionally, liquids can be measured or weighed to determine the amount consumed without real-time sens...
Article
Full-text available
Memories are a product of the concerted activity of many brain areas. Deregulation of consolidation and reprocessing of mnemonic traces that encode fearful experiences might result in fear-related psychopathologies. Here, we assessed how pre-established memories change with experience, particularly the labilization/reconsolidation of memory, using...
Article
Full-text available
Physical activity is a critical behavioral variable in many research studies and is, therefore, important to quantify. However, existing methods for measuring physical activity have limitations which include high expense, specialized caging or equipment, and high computational overhead. To address these limitations, we present an open-source, cost-...
Article
Full-text available
The direct and indirect pathway striatal medium spiny neurons (dMSNs and iMSNs) have long been linked to action selection, but the precise roles of these neurons in this process remain unclear. Here, we review different models of striatal pathway function, focusing on the classic “go/no-go” model which posits that dMSNs facilitate movement while iM...
Article
Full-text available
Feeding is a critical behavior that animals depend on for survival, and pathological alterations in food intake underlie disorders such as obesity and anorexia nervosa. To understand these disorders and their development in animal models, researchers must quantify food intake. Although conceptually straightforward, it remains a challenge to obtain...
Article
Full-text available
The obesity epidemic is a leading cause of health problems in the United States, increasing the risk of cardiovascular, endocrine, and psychiatric diseases. Although many people lose weight through changes in diet and lifestyle, keeping the weight off remains a challenge. Here, we discuss a hypothesis that seeks to explain why obesity is so persist...
Article
Full-text available
Objective Ad libitum high‐fat diets (HFDs) spontaneously increase caloric intake in rodents, which correlates positively with weight gain. However, it remains unclear why rodents overeat HFDs. This paper investigated how changing the proportion of diet that came from HFDs might alter daily caloric intake in mice. Methods Mice were given 25%, 50%,...
Article
Full-text available
The central adenosine system and adenosine receptors play a fundamental role in the modulation of dopaminergic neurotransmission. This is mostly achieved by the strategic co-localization of different adenosine and dopamine receptor subtypes in the two populations of striatal efferent neurons, striatonigral and striatopallidal, that give rise to the...
Article
Full-text available
The striatum controls food-related actions and consumption and is linked to feeding disorders including obesity and anorexia nervosa. Two populations of neurons project from the striatum: direct pathway medium spiny neurons (dMSNs) and indirect pathway medium spiny neurons (iMSNs). The selective contribution of dMSNs and iMSNs to food-related actio...
Article
Background The ability to appropriately integrate and respond to rewarding and aversive stimuli is essential for survival. The ventral pallidum (VP) plays a critical role in processing both rewarding and aversive stimuli. However, the VP is a heterogeneous structure, and how VP subpopulations integrate into larger reward networks to ultimately modu...
Article
Full-text available
The identification of distinct cell types in the basal ganglia has been critical to our understanding of basal ganglia function and the treatment of neurological disorders. The external globus pallidus (GPe) is a key contributor to motor suppressing pathways in the basal ganglia, yet its neuronal heterogeneity has remained an untapped resource for...
Article
Full-text available
Food intake measurements are essential for many research studies. Here, we provide a detailed description of a novel solution for measuring food intake in mice: the Feeding Experimentation Device (FED). FED is an open-source system that was designed to facilitate flexibility in food intake studies. Due to its compact and battery powered design, FED...
Article
Full-text available
Exercise is a common component of weight loss strategies, yet exercise programs are associated with surprisingly small changes in body weight [1-4]. This may be due in part to compensatory adaptations, in which calories expended during exercise are counteracted by decreases in other aspects of energy expenditure [1, 5-10]. Here we examined the rela...
Chapter
Over the past two decades, there has been an explosion of tools that allow researchers to manipulate and observe the function of specific neural populations and their projections. These tools, including optogenetics, chemogenetics, cell-type-specific ablation, and fluorescent calcium indicators, have been especially useful in studying the function...
Article
Full-text available
Obesity is associated with physical inactivity, which exacerbates the health consequences of weight gain. However, the mechanisms that mediate this association are unknown. We hypothesized that deficits in dopamine signaling contribute to physical inactivity in obesity. To investigate this, we quantified multiple aspects of dopamine signaling in le...
Conference Paper
Full-text available
In recent years, researchers and laboratory support companies have recognized the utility of automated profiling of laboratory mouse activity and behavior in the home-cage. Video-based systems have emerged as a viable solution for non-invasive mouse monitoring. Wider use of vision systems for ethology studies requires the development of scalable ha...
Article
Full-text available
Obesity is associated with physical inactivity, which exacerbates the negative health consequences of obesity. Despite a wide consensus that people with obesity should exercise more, there are few effective methods for increasing physical activity in people with obesity. This lack is reflected in our limited understanding of the cellular and molecu...
Article
A central theory of basal ganglia function is that striatal neurons expressing the D1 and D2 dopamine receptors exert opposing brain-wide influences. However, the causal influence of each population has never been measured at the whole-brain scale. Here, we selectively stimulated D1 or D2 receptor-expressing neurons while visualizing whole-brain ac...
Article
Full-text available
Bradykinesia is a prominent phenotype of Parkinson’s disease, depression, and other neurological conditions. Disruption of dopamine (DA) transmission plays an important role, but progress in understanding the exact mechanisms driving slowness of movement has been impeded due to the heterogeneity of DA receptor distribution on multiple cell types wi...
Article
Full-text available
The operant conditioning chamber is a cornerstone of animal behavioral research. Operant boxes are used to assess learning and motivational behavior in animals, particularly for food and drug reinforcers. However, commercial operant chambers cost several thousands of dollars. We have constructed the Rodent Operant Bucket (ROBucket), an inexpensive...
Article
Full-text available
It is widely believed that substance use disorder (SUD) results from both pre-alterations (vulnerability) and/or post-alterations (drug effects) on cortico-striatal circuits. These circuits are essential for cognitive control, motivation, reward dependent learning, and emotional processing. As such, dysfunctions in cortico-striatal circuits are tho...
Article
Full-text available
The striatum mediates a variety of functions including movement, decision-making, motivation, and reward learning. In vivo recording is a powerful technique that allows for the interrogation of these striatal functions while an animal is awake and behaving. Here, we describe equipment needed and general setup for performing in vivo electrophysiolog...