What individual differences in neural activity predict the future escalation of alcohol drinking from casual to compulsive? The neurobiological mechanisms that gate the transition from moderate to ...compulsive drinking remain poorly understood. We longitudinally tracked the development of compulsive drinking across a binge-drinking experience in male mice. Binge drinking unmasked individual differences, revealing latent traits in alcohol consumption and compulsive drinking despite equal prior exposure to alcohol. Distinct neural activity signatures of cortical neurons projecting to the brainstem before binge drinking predicted the ultimate emergence of compulsivity. Mimicry of activity patterns that predicted drinking phenotypes was sufficient to bidirectionally modulate drinking. Our results provide a mechanistic explanation for individual variance in vulnerability to compulsive alcohol drinking.
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. However, RPE cannot describe multiple phenomena to which dopamine is inextricably linked, such as behavior driven by aversive and neutral stimuli. We combined a series of behavioral tasks with direct, subsecond dopamine monitoring in the NAc of mice, machine learning, computational modeling, and optogenetic manipulations to describe behavior and related dopamine release patterns across multiple contingencies reinforced by differentially valenced outcomes. We show that dopamine release only conforms to RPE predictions in a subset of learning scenarios but fits valence-independent perceived saliency encoding across conditions. Here, we provide an extended, comprehensive framework for accumbal dopamine release in behavioral control.
•NAc core dopamine only mimics reward prediction error in select reward contexts•RPE does not model dopamine release during negative reinforcement•Dopamine signaling in the NAc core does not support valence-free prediction error•NAc core dopamine tracks valence-free perceived saliency in all conditions
Kutlu et al. examine dopaminergic information encoding in the nucleus accumbens. This work revises the long-held theory of dopamine as a reward prediction molecule and provides a novel framework for dopamine as a perceived saliency signal. These results unite multiple theories of dopamine signaling and have broad implications for psychopathologies.
•Dopamine has diverse actions on prefrontal cortex physiology and function.•The mesocortical dopamine pathway is uniquely sensitive to aversive stimuli.•Dopamine differentially influences ...projection-defined prefrontal subpopulations.•By calibrating distinct prefrontal outputs, dopamine sets the stage for aversive processing.
Decades of research suggest that the mesocortical dopamine system exerts powerful control over mPFC physiology and function. Indeed, dopamine signaling in the medial prefrontal cortex (mPFC) is implicated in a vast array of processes, including working memory, stimulus discrimination, stress responses, and emotional and behavioral control. Consequently, even slight perturbations within this delicate system result in profound disruptions of mPFC-mediated processes. Many neuropsychiatric disorders are associated with dysregulation of mesocortical dopamine, including schizophrenia, depression, attention deficit hyperactivity disorder, post-traumatic stress disorder, among others. Here, we review the anatomy and functions of the mesocortical dopamine system. In contrast to the canonical role of striatal dopamine in reward-related functions, recent work has revealed that mesocortical dopamine fine-tunes distinct efferent projection populations in a manner that biases subsequent behavior towards responding to stimuli associated with potentially aversive outcomes. We propose a framework wherein dopamine can serve as a signal for switching mPFC states by orchestrating how information is routed to the rest of the brain.
Alcohol and drug use can dysregulate neural circuit function to produce a wide range of neuropsychiatric disorders, including addiction. To understand the neural circuit computations that mediate ...behavior, and how substances of abuse may transform them, we must first be able to observe the activity of circuits. While many techniques have been utilized to measure activity in specific brain regions, these regions are made up of heterogeneous sub-populations, and assessing activity from neuronal populations of interest has been an ongoing challenge. To fully understand how neural circuits mediate addiction-related behavior, we must be able to reveal the cellular granularity within brain regions and circuits by overlaying functional information with the genetic and anatomical identity of the cells involved. The development of genetically encoded calcium indicators, which can be targeted to populations of interest, allows for in vivo visualization of calcium dynamics, a proxy for neuronal activity, thus providing an avenue for real-time assessment of activity in genetically and anatomically defined populations during behavior. Here, we highlight recent advances in calcium imaging technology, compare the current technology with other state-of-the-art approaches for in vivo monitoring of neural activity, and discuss the strengths, limitations, and practical concerns for observing neural circuit activity in preclinical addiction models.
•Calcium imaging allows for overlaying functional activity with cell identity.•Recently, this technology has become feasible for use outside the optics field.•There are unique considerations for using this approach in alcohol abuse models.
Textile dyes and their residues gained growing attention worldwide. Textile industry is a strong water consumer potentially releasing xenobiotics from washing and rinsing procedures during finishing ...processes. On a decentralised basis, also final consumers generate textile waste streams. Thus, a procedure simulating home washing with tap water screened cotton textiles leachates (n = 28) considering physico-chemical (COD, BOD
5
, and UV absorbance) and ecotoxicological data (
Daphnia magna, Pseudokirchneriella subcapitata
and
Lepidium sativum
). Results evidenced that: (i) leachates presented low biodegradability levels; (ii) toxicity in more than half leachates presented slight acute or acute effects; (iii) the remaining leachates presented “no effect” suggesting the use of green dyes/additives, and/or well established finishing processes; (iv) no specific correlations were found between traditional physico-chemical and ecotoxicological data. Further investigations will be necessary to identify textile residues, and their potential interactions with simulated human sweat in order to evidence potential adverse effects on human health.
Neurobiology of novelty seeking Farahbakhsh, Zahra Z; Siciliano, Cody A
Science (American Association for the Advancement of Science),
05/2021, Letnik:
372, Številka:
6543
Journal Article
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. These processes can occur via homosynaptic mechanisms—such as presynaptic dopamine autoreceptors and dopamine transporters ‐ as well heterosynaptic mechanisms such as retrograde signaling from postsynaptic cholinergic and dynorphin systems, among others. Additionally, modulation of dopamine release via diffusible messengers, such as nitric oxide and hydrogen peroxide, allows for various metabolic factors to quickly and efficiently regulate dopamine release and subsequent signaling. Here we review how these mechanisms work in concert to influence the timing and magnitude of striatal dopamine signaling, independent of action potential activity at the level of dopaminergic cell bodies in the midbrain, thereby providing a parallel pathway by which dopamine can be modulated. Understanding the complexities of local regulation of dopamine signaling is required for building comprehensive frameworks of how activity throughout the dopamine system is integrated to drive signaling and control behavior.
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. Dopamine release at terminals in the striatum can be modulated by a variety of mechanisms, including homosynaptic mechanisms intrinsic to the cell itself and heterosynaptic mechanisms that integrate activity of local microcircuitry. Together, these mechanisms work in concert to dynamically regulate dopamine release, uptake and repackaging for future release events, and thus exert precise control over dopaminergic activity. Here we review how these mechanisms work together to influence the timing and magnitude of striatal dopamine signaling, independent of action potential activity at the level of dopaminergic cell bodies in the midbrain, thereby providing a parallel pathway by which dopamine can be modulated.
Although the dopamine transporter (DAT) is the primary site of action for cocaine, and the dopamine system is known to mediate the reinforcing effects of cocaine, the dopaminergic variations ...underlying individual differences in cocaine self-administration behaviors are not fully understood. Recent advances in the application of economic principles to operant tasks in rodents have allowed for the within-subject, within-session determination of both consummatory and appetitive responding for reinforcers. Here we combined a behavioral economics approach with cocaine self-administration and ex vivo voltammetric recording of dopamine signaling in the core of the nucleus accumbens of rats to determine the relationship between dopamine signaling and discrete aspects of cocaine taking and seeking. We found neither dopamine release or uptake tracked individual differences in cocaine consumption or the reinforcing efficacy of cocaine. Cocaine potency at the DAT was correlated with reinforcing efficacy, but was not related to cocaine consumption. Further, we introduce a novel analysis that determines perseverative responding within the same procedure, and find that cocaine potency at the DAT also tracks differences in perseverative responding. Together, we demonstrate that cocaine effects at the DAT determine the reinforcing efficacy of cocaine, and perseverative responding for sub-threshold doses of cocaine that do not maintain responding when presented in isolation. Surprisingly, we find that variations in cocaine potency do not account for differences in cocaine consumption, suggesting that satiation for cocaine is determined by other targets or mechanisms. Finally, we outline a novel approach for relating drug-target interactions and potency to discrete motivational states during a single self-administration session.
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