Program

To study the neural circuitry, the action of one cells under the context of others, one would precisely measure and perturb specific neuronal populations and molecules in behaving animals who are specifically engaged in performing the computation or function of interest. The dataset of millions of neurons firing together underlying a behavior are required to develop and refine theories (hypotheses) explaining animal behavior in terms of brain physiology. The focus of lab is to develop novel genetically encoded indicators based on fluorescence proteins, especially focusing on direct and specific measurement of myriad input signals with needed spatial and temporal resolutions. In this talk, I will discuss our recent progress into develop and apply a new suite of genetically encoded indicators of neural activity. I will discuss the design, characterization and applications of these genetically encoded indicators. We also validate our sensor design platform, which could also be applied to developing sensors for a broad range of neuromodulators, including norepinephrine, serotonin, melatonin, and opioid neuropeptides. In combination with calcium imaging and optogenetics, these sensors are well poised to permit direct functional analysis of how the spatiotemporal coding of neural input signaling mediates the plasticity and function of target circuits.

Stephan Lammel¹, Mitsuko Uchida², Markita Landry¹, Tianyi Mao³

¹UC Berkeley, ²Harvard University, ³Vollum Institute

Great strides have been made towards understanding the diversity of midbrain dopamine neurons. Recent studies suggest that rather than a single functional unit, dopamine neurons form distinct groups at anatomical, molecular and functional levels contributing to the signaling of reward, aversion, salience, novelty and locomotion. This panel will highlight the development of novel optical tools and imaging approaches, as well as the application of cutting-edge tools to add important information to the rapidly progressing dissection of heterogeneous dopamine signaling in health and disease. Markita Landry (UC Berkeley) will discuss the development of a near-infrared nanosensor (nIRCats) that can measure dopamine transmission in acute brain slices and detect dopamine efflux in the extracellular space driven by electrical or optogenetic stimulation. Tianyi Mao (Vollum Institute) will present the development of novel PKA and cAMP fluorescence sensors, which combined with modern microscopy can image intracellular responses to endogenous dopamine release at single-cell and subcellular resolutions in brain slices and behaving animals. Mitsuko Watabe-Uchida (Harvard University) will introduce how posterior tail of the striatum-projecting dopamine neurons form a unique subgroup of dopamine neurons and discuss why multiple axes of dopamine evaluation systems are advantageous for reinforcement learning. Stephan Lammel (UC Berkeley) will discuss how developing a detailed understanding of subregion-specific dopamine signaling in the nucleus accumbens contributes to the anatomical and functional diversity of dopamine neurons and may represent an important step towards the identification of clinically-relevant targets for treating impulse control disorders. Taken together, this panel will cover technology development and biological applications that allow exciting progress in understanding the structural and functional heterogeneity of the dopamine system. 

Clifford Cassidy¹, Luigi Zecca², Ioannis Isaias³, Matthew Betts⁴

¹The University of Ottawa, ²Institute of Biomedical Technology, ³University Hospital Würzburg, ⁴University of Magdeburg

Establishing new methods to interrogate the status of the dopamine and noradrenaline systems in the human brain in vivo is needed to promote research and treatment in neuropsychiatric illness. Over recent years, diverse applications have been developed for a novel family of MRI sequences, known as neuromelanin-sensitive MRI. In this symposium, the biology of neuromelanin will be reviewed to indicate the relevance of neuromelanin content to the health and function of catecholamine neurons. The well-established use of this method as a marker of neurodegeneration in the substantia nigra in Parkinson’s disease will be reviewed as well as more recent applications of this technique as an assay of dopamine function and marker of dopamine dysregulation in psychotic illness. Finally, measurement of NM-MRI signal in the locus coeruleus to probe the integrity of the noradrenergic system will be reviewed.

Kim Neve¹, Jonathan Javitch², Chris Ford³, Jean Martin Beaulieu⁴

¹VA Portland Health Care System, ²Columbia University/New York State Psychiatric Institute, ³University of Colorado School of Medicine, ⁴University of Toronto

Recent technological advances have greatly enhanced our ability to move rapidly from molecular-level studies of protein function and signal transduction to behavioral and translational studies. The speakers in this session will present work on the dopamine D2 receptor that extends the full range of that spectrum. Chris Ford has characterized synaptic activation of D2 receptors on medium spiny neurons in the murine striatum and nucleus accumbens. He will describe differences in kinetics and sensitivity of the receptors between these two regions and how exposure to cocaine leads to region-specific alterations in D2 receptor sensitivity. Jonathan Javitch will describe the design and characterization of D2 receptors biased towards interactions with arrestin or G proteins and will show data elucidating the relationship between this signaling bias and D2 receptor-mediated behaviors. Kim Neve will discuss the in vitro and in vivo functional consequences of splice and allelic variation of the D2 receptor. Martin Beaulieu has used high-precision intersectional approaches to characterize cerebral cortical neurons that express the D2 receptor and modify gene expression in these cells. He will discuss the relationship of cortical D2 receptor signaling to emotional and cognitive functions that may be involved in mental illnesses.

Vincent Seutin¹, Zayd Khaliq², Jean-Marc Goaillardr4, Carlos Paladini³

¹Liège University, ²NIH, ³University of Texas at San Antonio, 4 Université of Aix Marseille

In the last few years, progress has been made on several fronts in this area. Vincent Seutin will describe experiments suggesting a hereto unknown mechanism for the characteristic slow pacemaking of these neurons. Zayd Khaliq will describe experiments showing physiological properties of axonal conduction in these neurons, a completely new topic in the dopamine field. Jean Marc Goaillard will describe his recent work on the morphological and biophysical determinants of action potential shape and pacemaking in these neurons. Carlos Paladini will show results of in vivo patch clamp experiments demonstrating how the waveform of subthreshold membrane potential fluctuations relates to their firing properties.

Kelly Tan¹, Talia Lerner², Elizabeth Steinberg³, Benjamin Saunders⁴

¹Biozentrum, University of Basel, ²Northwestern Feinberg School of Medicine, ³Stanford University, ⁴University of Minnesota

Dopamine is well known both for its roles in reward processing and in action selection, but these roles are often studied in isolation. This symposium will go in depth to explore how interactions between heterogeneous populations of dopamine neurons translate motivational states into motor patterns, bridging two areas of study and providing unique insights into the dopaminergic coordination of motivated behavior.

Louis-Eric Trudeau¹, Pascal Kaeser², Ulrik Gether³, Zachary Freyberg⁴

¹Université de Montréal, ²Harvard University, ³University of Copenhagen, ⁴University of Pittsburgh

Compared to neurons using classical fast synapses, we presently know very little about the connectivity mediated by neurons releasing modulatory neurotransmitters such as dopamine, which signal through release sites that do not conform to the classical synaptic model. In this session, the four speakers will present new discoveries on the structure and function of dopaminergic axon terminals.

Marco Leyton¹, Isabelle Boileau², David Zald³, Eleanor Simpson⁴

¹McGill University, ²CAMH, University of Toronto, ³Vanderbilt University, ⁴Columbia University

What is the role of D2/3 receptors in reward-related behaviors? The answer has proven to be more complex than previously envisaged. The present speakers’ combination of correlational studies in humans and causality testing in rodents extends our understanding of the influence of temporal factors, spatial factors and receptor subtypes, indicates that both increases and decreases in DR2/3 transmission can be disruptive, and clarifies previously reported superficially contradictory findings.

Nina Karalija¹, Alireza Salami², Goran Papenberg³, Jarkko Johansson¹

¹Umeå university, ²Umeå university and Aging Research Center, Karolinska Institute and Stockholm University, ³Aging Research Center, Karolinska Institute and Stockholm University

This symposium will address interindividual differences and decline of dopamine receptor systems during normal (non-pathological) aging. The presentations will demonstrate interrelations between D1 and D2-receptor availability, their contributions to various cognitive domains in old age, their associations to brain structure and function, and their interactions with lifestyle and genetic variations.

Jeroen Pasterkamp¹, Sandra Blaess², Martin Levesque³, Jens Schwamborn⁴

¹University Medical Center Utrecht, ²University of Bonn, ³Université Laval, ⁴University of Luxembourg

It is becoming clear that the midbrain dopamine system is rather heterogeneous. How this heterogeneity is established and how different dopamine neuron subtypes function remains incompletely understood.

Heinz Steiner¹, Carlos Bolanos², Panayotis Thanos³, Micky Marinelli⁴

¹RFUMS/Chicago Medical School, ²Texas A&M University, ³University at Buffalo, ⁴University of Texas at Austin

Psychostimulant plus antidepressant co-exposure occurs in treatment of ADHD/depression comorbidity (~40% of ADHD) and with psychostimulant abuse in patients on antidepressants. We will discuss how SSRI antidepressants potentiate neuronal and behavioral effects of psychostimulants, including effects on gene regulation, functional brain connectivity, reward and cocaine self-administration, in rats. Our findings indicate that psychostimulant+SSRI co-exposure may increase addiction liability.

Dysfunctional dopamine (DA) signaling has been associated with a broad spectrum of neuropsychiatric disorders, prompting investigations into how midbrain DA neuron heterogeneity may underpin this variety of behavioral symptoms. Recognizing the need for a systematic classification scheme, we and others have catalogued DA neurons based on their gene expression profiles. Here I will synthesize points of congruence, but also highlight key differences, between these molecular classification schemes. In doing so, I hope to provide an initial framework that will facilitate investigations into the functions of these putative DAergic subtypes. Next, I will discuss recent studies on the developmental basis of DA neuron diversity. Our lab has previously described the floor plate origin of DA neurons. Here I will discuss recent studies that suggest that molecular subdivisions in the floor plate, at least in part, underpin DA neuron diversity.

More information to come

There is a strange disconnect in how we typically think about dopamine. On the one hand, there is broad consensus that dopamine is a critical modulator of motivation. On the other, our predominant theory – that dopamine signals reward prediction errors – is not about motivation at all, but rather learning. In recent years we have attempted to bridge this gap, demonstrating that dopamine fluctuations can track convey motivational signals in specific forebrain subregions, even when midbrain dopamine cell firing does not. Yet this has proven controversial, with some continuing to interpret all dopamine fluctuations as reward prediction errors. I will present our latest contributions to this debate, including new results on how dopamine signals are regulated to drive motivated behavior.

Jeremy Day¹, Colleen McClung², Ian Maze³, Erin Calipari⁴

¹University of Alabama at Birmingham, ²University of Pittsburgh, ³Mt. Sinai School of Medicine, ⁴Vanderbilt University

Genetic and epigenetic regulatory mechanisms exert tremendous control over nearly all aspects of dopamine neurotransmission, and alterations in these processes have been linked to numerous neuropsychiatric disorders. The goal of this session is to communicate cutting-edge research into our understanding of how these mechanisms influence reward circuit function and drug-seeking behaviors.

Véronique Deroche-Gamonet¹, Terry Robinson², Anna Samaha³, Marco Venniro⁴

¹Université de Bordeaux, ²University of Michigan, ³Université de Montréal, ⁴National Institute on Drug Abuse, National Institutes of Health

Addiction research relies heavily on preclinical models, where animals self-administer drugs voluntarily. Animal research has made great contributions to our current understanding of addiction, but it has not yet met the urgent need for new treatment approaches. This may be because present preclinical approaches do not adequately reflect the human situation. Here we present novel approaches that might help remedy this.

Katlin Silm¹, Margaret Rice², Susana Mingote³, Vivien Zell⁴

¹University of California San Francisco, ²New York University, ³Advance Science Research Center/City University of New York, ⁴University of California San Diego

It is now well established that subsets of midbrain dopamine neurons can store and co-release the major excitatory and inhibitory neurotransmitters, glutamate and GABA. However, basic physiological and functional roles of these signals are only just beginning to come into focus. This symposium will explore recent findings on the physiological mechanisms that regulate the synaptic release of co-transmitters, their effects on defined post-synaptic cells, as well as their roles in shaping behavior.

Gilberto Fisone¹, Pierre-Olivier Fernagut², Maria Rodriguez Oroz³, Antonio Strafella⁴, Raffaekka Tonini⁵

¹Karolinska Institutet, ²INSERM U1084, University of Poitiers, ³University of Navarra, ⁴University of Toronto, ⁵Italian Institute of Technology

In Parkinson’s disease administration of dopaminergic drugs leads to the emergence of impulsive/compulsive disorders and addictive-like behavior, which negatively affect the quality of life of patients and are still poorly understood. This Symposium will discuss the mechanisms and neural systems implicated in these neuropsychiatric complications presenting a series of basic and clinical studies ranging from experimental modeling to advanced imaging analyses.

Martin Parent¹, Philippe Huot², Christopher Bishop³, Véronique Sgambato⁴

¹Université Laval, ²McGill University, ³Binghamton University, ⁴CNRS

This session will revolve around the interactions between DA and 5-HT systems involved in the expression of motor and non-motor symptoms that are experienced by PD patients, and will address the growing interest in the fate of 5-hydroxytryptamine (serotonin or 5-HT) neurons in Parkinson’s disease (PD).

Nao Chuhma¹, Naoshige Uchida², Jochen Roeper³, Mark Howe⁴

¹Columbia University, ²Harvard University, ³Goethe University Frankfurt, ⁴Boston University

The functional diversity of midbrain DA neurons ranges across multiple scales. Speakers will address distinct biophysical features of projection-defined DA neuron subpopulations, diversity of encoding of reward prediction error signals underpinning improvement in reinforcement learning, heterogeneity in DA neuron synaptic actions in the striatum, and how spatiotemporal variations in DA axonal signals contribute to spontaneous movements and unpredicted rewards across striatal territories.

Jessica Perkins¹, Jill Crittenden², Fumino Fujiyama³, Nadine Gut⁴

¹University of Texas at San Antonio, ²Massachusetts Institute of Technology, ³Doshisha University, ⁴Rutgers University

Inhibition of DA activity has been associated with reduced motor performance and encoding of negative reward prediction error, but how different sources of inhibition contribute to DA activity in the SNc and how they shape behavior is not well understood. We will address the different components of the inhibitory afferent circuitry using a variety of tools to describe the connectivity of GABAergic afferents and their effects on DA neurons, and the behavioral consequences of this inhibition.

Lauren Faget¹, Jasper Heinsbroek², Mary Kay Lobo³, Steve Mahler⁴

¹Univeristy of California San Diego, ²University of Colorado Denver – Anschutz Medical Campus, ³University of Maryland, School of Medecine, ⁴University of California, Irvine

The ventral pallidum has recently emerged as an underappreciated, but critical player in the regulation of physiological and pathological dopamine signaling. This panel brings new light on how heterogeneous VP neurons, as well as their inputs and outputs, impact motivated behaviors, and contribute to maladaptive behaviors related to abnormal dopamine signaling.

Geoffrey Schoenbaum¹, Yael Niv², Thorsten Kahnt³, Peter Shizgal⁴

¹National Institute on Drug Addiction, ²Princeton, ³Northwestern University, ⁴Concordia University

Recent data poses challenges to model-free approaches of dopamine signaling. The present symposium will address the constrains of the model-free hypothesis and how can they be resolved.

Patricia Silveira¹, Cecilia Flores¹, Francesco Papaleo², Catherine Peña³

¹McGill University, ²Istituto Italiano di Tecnologia, ³Princeton

In this symposium, we will present multidisciplinary and translational data from different labs demonstrating that dopamine neurotransmission is a key modulator of the effects of early life adversity on neurodevelopment and risk for psychopathology.

Since the 1990s, thinking about the role of dopamine (DA) in the regulation of basal ganglia circuitry and movement has focused on the striatum. This single-mindedness is particularly evident in models of movement disorders, like Parkinson’s disease (PD). However, DA signaling takes place throughout the basal ganglia. Indeed, new progressive models of PD suggest that while striatal DA release is critical for associative learning and action sequences, it is not necessary for simple ambulation. This recognition has implications not only for how we think about DA control of movement, but how we approach treating movement disorders, like PD.

 The susceptibility to develop drug addiction differs substantially between individuals. Among the predictive factors that have been implicated are personality traits such as impulsivity, exploration or novelty seeking. Using an interdisciplinary approach that combines electrophysiology, genetic manipulation of circuits and behavioral analysis, we analyze exploratory behaviors and reactions to uncertainty, two major components of mouse personality, and link modifications of midbrain dopamine cells to modulation of such behaviors. By analyzing mice behaviors in a semi-naturalistic environment, we also explore the causal role of social relationships in the shaping of intra-individual behavioral variabilities. We notably showed that the composition of social groups affects non-social behavioral traits and the underlying decision-making system. By acting on the dopamine system, the social context may indeed affect the capacity of individuals to make decisions and consequently their vulnerability to drugs of abuse.

Ingo Willuhn¹, Lauren Burgeno²

¹Netherlands Institute for Neuroscience, ²University of Oxford

Dopamine function is shaped by anatomical organization and connectivity. Dopamine cell-cluster and projection-target sub-systems, as well as axonal regulation of dopamine neurons, have diverse behavioral implications. This panel will present novel insights on the behavioral impact of such systems – detailing and integrating the cellular and regional specificity of dopamine signaling by applying an array of cutting-edge in vivo techniques supporting high temporal and spatial resolution.

James Daniel⁴, John Williams¹, Yulong Li², Stephani Gantz³

¹Vollum Institute, ²Peking University, ³National Institute on Drug Abuse (NIDA), ⁴Max Planck Institute of Experimental Medicine

 

Given the importance of dopamine in brain function and behavior, it is essential to understand the molecular regulation of dopamine secretion and its dysfunction in disease. Recently, several innovative approaches to studying dopamine release have been developed, allowing deeper insight into dopaminergic transmission. This symposium focuses on recent breakthroughs in deciphering the molecular regulation of dopamine based on innovative methodologies to detect released dopamine.

Randy Blakely¹, Sara Jones², Aurelio Galli³, Ali Salahpour⁴

¹FAU Brain Institute, ²Wake Forest, ³University of Alabama in Birmingham, ⁴Dr.

This symposium is focused on dopamine transporter. Presenters will discuss published and unpublished data using a variety of approaches to interrogate how drugs, interacting proteins and disease causing mutants impair/affect transporter function. Each presenter will also discuss different pharmacological interventions that can be used to rectify the various DAT impairments described in their presentations. 

Ashley Kopec¹, John Meitzen², Alexa Veenema³, Nicola Grissom⁴

¹Albany Medical College, ²North Caroline State University, ³Michigan State University, ⁴University of Minnesota Twin Cities

Behaviors supported by the dopaminergic ‘reward’ circuitry of the brain have broad relevance to many mental health disorders in humans. Neurological disorders often present in sex-specific ways, but how sex differences manifest is an active area of research. This symposium will focus on the sex-specific development and utilization of dopaminergic systems at cellular, molecular, genetic, circuit, and behavioral levels, with implications for behavioral outcomes in health and disease.

Catharine Winstanely¹, Melissa Sharpe², Thomas Stalnaker³, Mihaela Iordanova³

¹University of British Columbia, ²University of California Los Angeles, ³Concordia University

The hypothesis that mesolimbic dopamine signals reward prediction error has fascinated the field of neuroscience. This symposium will delve deeper into the conditions that define this signal and its influence over learning and motivated behaviour. The studies presented will explore circuit dynamics within and beyond the realm of reward.

Freja Herborg¹, David Sulzer², Robert Edwards³, Anne Bassett⁴

¹University of Copenhagen, ²Columbia University, ³UCSF School of Medicine, ⁴University of Toronto

Dopamine plays an essential role in neuropsychiatric and neurodegenerative diseases but classically these two groups of diseases have been viewed as distinct pathologies. This session will present novel insights into shared pathobiological mechanisms with focus on results from new genetic mouse models, large-scale exome sequencing data, mechanisms of altered dopamine release patterns, role of alpha-synuclein in exocytotic monoamine release, and phenotypic spectrum of 22q11.2 deletion syndrome.

Pierre Trifilieff¹, Marco Niello², Nathalie Ginovart³, Matthaeus Willeit², Harald Sitte²

¹INRA, ²Medical University of Vienna, ³University of Geneva

Altered reward processing is a key element in the pathogenesis of psychiatric disorders. Assembling scientists engaged in molecular, behavioral, and clinical studies, this symposium will focus on alterations in dopamine (DA) signalling affecting the physiological functions of DA in dopaminergic and dopaminoceptive neurons.

Marco Capogna¹, Jesper Sjöström², Jeff Wickens³, Laurent Venance⁴, Emma Louth¹

¹University of Aarhus, ²McGill University, ³Okinawa Institute of Science and Technology Graduate University, ⁴CNRS/ UMR 7241 – INSERM U1050

Experience-dependent plasticity at excitatory synapses within neuron circuits involving dopamine is likely to represent a fundamental cellular mechanism that enables a wide range of positive and negative reinforcement learning strategies. In this symposium, we will discuss the neuromodulatory role of dopamine on Spike-Timing-Dependent Plasticity (STDP) a salient cellular model of reward learning and memory. First, Jesper Sjöström, Montreal, Canada, will introduce the concept of STDP, a temporally asymmetric form of Hebbian learning induced by tight temporal correlations between the spikes of pre- and postsynaptic neurons. The second speaker, Jeff Wickens, Okinawa, Japan, will propose that dopamine-dependent STDP at striatal synapses represents a striking cellular mechanism to explain the retroactive effect of dopamine in reinforcing past behaviour. The action of dopamine on STDP at striatal synapses will be also the focus of the talk presented by Laurent Venance, Paris, France. Particularly, he will show experimental and computer-modelling data on dopamine-endocannabinoid interactions that mediate bidirectional STDP in the striatum. The speaker will emphasize that this novel mechanism could also be implicated in basal ganglia pathophysiology. Finally, Emma Louth, Aarhus, Denmark, will compare neuromodulatory actions exerted by dopamine on STDP evoked at excitatory cortical synapses in adult mouse and in surgically-resected human cortical tissue. Thus, the symposium will provide an exciting overview on the work in progress on the role of dopamine on synaptic plasticity in cortical and striatal circuits. We are confident that the topic will attract a broad audience including experts or students of synaptic physiology, neuropharmacology, computer modelling and neurology.

Todd Doran¹, Theresa H Hastings², Luigi Bubacco³, Jonathan Doorn⁴

¹University of Minnesota, ²University of Pittsburgh, ³University of Padova, ⁴University of Iowa

Selective degeneration of dopaminergic neurons is the cause of motor symptoms during Parkinson’s disease (PD). The toxicity of dopamine and its metabolites are hypothesized to play a causal role in PD. Dopamine auto-oxidation generates reactive electrophilic small molecules that modify proteins and influence their function. This symposium will discuss methods that enable functional and structural characterization of these reactive species and their biomolecular adducts.

Peter Magill¹, Kathrine Brimblecombe¹, Jörg Striessnig², Nadine Ortner², Birgit Liss³

¹Oxford University, ²Innsbruck University, ³Ulm University

We propose a symposium to address the interplay of Cav channels, Ca2+ homeostasis, and α-synuclein load in context of the selective vulnerability of dopaminergic neurons in brain disorders, in particular in Parkinson’s disease. The proposed 4 speakers represent a balanced mix of females / males and of junior / intermediate / senior scientists, covering a broad range of different aspects of the proposed topic. Please note that either Striessnig or Ortner will speak, the other would act as chair.

Dopamine (DA) in the mammalian striatum plays critical roles in motivation, action and reinforcement learning, and DA dysregulation underlies psychomotor disorders that include Parkinson’s disease and addictions. DA neurons in substantia nigra and ventral tegmental area generate action potentials at a range of instantaneous frequencies, but it is becoming evident that a mechanisms operating on the colossal branched arbours of DA axons govern whether dynamic activity in DA neurons is relayed into DA release. Our work in mouse striatum shows that a diverse range of mechanisms gate DA output, and these include other striatal circuits such as cholinergic interneurons, GABA tone and their regulators, as well as intrinsic regulators of short-term presynaptic plasticity including the DA transporter, and proteins associated with Parkinson’s. I will highlight our recent findings to illustrate how processes operating on DA axons powerfully filter DA output.

Dan Covey¹, Giovanni Hernandez², Natalie Zlebnik¹, Miriam Melis³

¹University of Maryland School of Medicine, ²McGill University, ³University of Cagliari

Chair: Joseph Cheer, University of Maryland School of Medicine. The endocannabinoid (eCB) system is an evolutionarily conserved signaling network that acts throughout the brain and periphery to regulate numerous homoeostatic processes. We will present recent work demonstrating that, by modulating dopamine function, eCB signaling controls various neural adaptations critical to normal learning and development. This work is timely and relevant given the spreading legalization of cannabis in North America and rising interest in cannabinoid-based therapies for neuropsychiatric disorders. A large body of work demonstrates that eCB manipulations potently alter reward-directed behavior. Dr. Covey will present findings showing that eCB signaling in the ventral tegmental area shapes neural circuit control of dopamine neurons and allows them to function as the canonical neural substrate of reward prediction during the pursuit of reward. Adolescence is a critical period for refinement and organization of dopamine neural circuitry. Dr. Hernandez will show that adolescent cannabinoid exposure increases susceptibility to depression and alters mesolimbic dopamine pathways later in life. Specifically, CB1 receptor agonist administration in adolescent mice disrupts responding to chronic social defeat stress in adulthood and alters levels of the microRNA miR-218 as well as those of Dcc receptors in the prefrontal cortex. Similarly, Dr. Zlebnik will present findings demonstrating that adolescent cannabinoid exposure dysregulates genes that orchestrate mesolimbic dopamine system development and induces aberrant addiction-related behaviors in adulthood, including potentiated cocaine-seeking behavior and its dopaminergic correlates. Finally, the work Dr. Melis will describe how prenatal cannabis exposure (PCE) predisposes offspring to various neuropsychiatric disorders. Her findings establish that PCE promotes molecular, cellular and synaptic changes resulting in a hyperdopaminergic phenotype in juvenile rat offspring.

Rodrigo Pachego⁴, Jennifer Felger³, Peter Gaskill², Habibeh Khoshbouei¹,

¹University of Florida, ²Drexel University, ³Emory University, ⁴Fundacion Ciencia & Vida

Although dopamine is widely studied for its role in CNS mediated neurological and neuropsychiatric diseases such as drug addiction, reward, learning and Parkinson’s diseases, a growing body of literature has demonstrated the importance of dopamine as an immunomodulatory factor and a neuro-immune mediator. Immune cells involved in both adaptive and innate immune responses, such as dendritic cells, T cells, B cells, and macrophages are capable of synthesizing and releasing dopamine into the extracellular compartment, thus enabling communications with different cell types in the periphery. These interactions not only suggest that dopamine can mediate communication between immune cells, but also may be involved in a bidirectional cross-talk between the immune and the nervous system. Indeed, the immunologic effects of dopamine has shown a substantial impact on immune cell function, and on the pathogenesis of several diseases. These include HIV infection, autoimmune diseases such as inflammatory bowel disease, Parkinson’s disease and cancer. However, the mechanisms regulating the impact of dopamine on these distinct pathologies remain unclear, as to the specific signaling pathways and neuro-immune interactions mediating these effects. This symposium will examine the disparate and common mechanisms involved in dopamine-mediated pathogeneses, bringing the immunologic impact of dopamine into wider focus. This will provide the conference with a novel perspective on the immunologic role of dopamine and potentially spur new insight and collaborations focused on targeting these pathways to amplify or ameliorate the positive and negative effects of dopamine on the etiology of disease.

Kuei Tseng¹, Rahul Chandrasekhar², Amy Newman³, Lauren Slosky²

¹College of Medicine – University of Illinois at Chicago (UIC), ²Duke University, ³NIDA-IRP, NIH

Chairs: Marc G. Caron, Duke University and Kuei Tseng, University of Illinois at Chicago. Dopamine (DA) is a major modulator of brain function that regulates executive function, motor control, motivation, arousal, reinforcement, and reward. This Parallel Session will demonstrate how using recently developed tools based of functional selectivity/ biased signaling at dopamine receptors can be used for potential therapeutic benefits.

Bruno Giros¹, Sebastian Haesler², Daniela Neuhofer³, Alban de Kerchove d’Exaerde⁴

¹McGill University, ²KU Leuven & Neuroelectronics Research Flanders, ³Medical University of South Carolina, ⁴Université Libre de Bruxelles (ULB)

Chairs: Bruno Giros, Alban de Kerchove d’Exaerde

Dopaminergic and dopaminoceptive systems are among the most studied because of their central roles in locomotion, the reward system, learning and many neuropsychiatric and cognition disorders. Despite these intensive studies, new roles and new circuits are constantly being discovered within the frame of the canonical direct (D1-MSNs) and indirect (D2-MSNs) striatal output and their complex regulation of the thalamo-cortico-striatal loop.

Jill Becker¹, Jennifer Zachry², Susan Andersen³, Adele Stewart⁴

¹University of Michigan, ²Vanderbilt University, ³McLean Hospital, ⁴Florida Atlantic University

This symposium will provide critical evidence demonstrating that genetic sex and sex hormones determine key elements of the dopamine system from development, to dynamic neurotransmission, to behavior and, ultimately, disease susceptibility.

Hui Zhang¹, Quyen Hoang², Mark Cookson³, Darren Moore⁴

¹Thomas Jefferson Univ., ²Indiana University School of Medicine, ³NIH, ⁴Van Andel Institute

Mutations in LRRK2 are the most common known genetic causes of Parkinson?s disease (PD). Given its strong genetic links, LRRK2 represents a compelling therapeutic target for PD. However, the mechanisms that regulate LRRK2 function and the pathogenic effects of mutations remain unclear. While studies have focused largely on LRRK2 kinase activity, attention on the GTPase activity is limited. In this symposium, we will discuss the importance of the GTPase domain for LRRK2-Linked PD Pathogenesis.

Christoph Kellendonk¹, Eduardo Gallo², Ana Rodrigues³, Johannes de Jong⁴, Veronica Alveraz⁵

¹Columbia University, ²Fordham University, ³University of Minho, ⁴University of California Berkeley, ⁵NIAAA

Extensive research has associated ventral striatal dopamine to reward-driven behavior. However, the underlying neurobiological mechanisms are still being explored. Newly developed tools in the mouse allow for cell type-specific circuit approaches that can help unravel these mechanisms in vivo.

Maria Concetta Miniaci¹, Paolo Calabresi², Elvira De Leonibus³, Sathya Puthanveettil⁴

¹University of Naples Federico II, ²Gemelli University Hospital, ³Institute of Neurobiology and Cellular Biology, ⁴The Scripps Research Institute

Neuromodulators, such as norepinephrine, serotonin, and dopamine have been implicated in the regulation of neuronal activity, synaptic plasticity, cognition and behavior across the lifespan. How these neurotransmitters shape neural activity during behavioral tasks and how they regulate synaptic transmission during memory formation is poorly understood. Understanding the mechanisms of monoamine synaptic modulation is of high clinical relevance since the neuromodulatory systems have been identified as a target of many pharmacological treatments for psychiatric and neurological conditions such as dementia, depression, anxiety, schizophrenia, and drug abuse.

Orexin (ox, also known as hypocretin) neurons of the lateral hypothalamus (LH) project widely through out the brain, including to the ventral tegmental area (VTA). Orexin signalling has been linked to many different behavioural phenotypes, but a recent hypothesis suggests that, across all domains, orexin plays a critical role in driving motivational activation. Orexin neurons are activated by internal, homeostatic or external, motivationally relevant signals and coordinate both psychological and physiological processes to facilitate adaptive behaviours. This presentation will focus on how orexin modulates drug-induced synaptic transmission in the VTA and related behavioural outcomes. Orexin is co-expressed with dynorphin, a kappa-opioid receptor agonist. These co-released peptides have opposing action on VTA dopamine firing and drug seeking behaviour. This presentation will also discuss potential consequences of co-release of these neuromodulators to dopamine neuronal activity and related behaviours.