Optogenetic Modulation of Neural Circuits that Underlie Reward Seeking

Department of Psychiatry, University of North Carolina Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Biological psychiatry (Impact Factor: 10.26). 12/2011; 71(12):1061-7. DOI: 10.1016/j.biopsych.2011.11.010
Source: PubMed


The manifestation of complex neuropsychiatric disorders, such as drug and alcohol addiction, is thought to result from progressive maladaptive alterations in neural circuit function. Clearly, repeated drug exposure alters a distributed network of neural circuit elements. However, a more precise understanding of addiction has been hampered by an inability to control and, consequently, identify specific circuit components that underlie addictive behaviors. The development of optogenetic strategies for selectively modulating the activity of genetically defined neuronal populations has provided a means for determining the relationship between circuit function and behavior with a level of precision that has been previously unobtainable. Here, we briefly review the main optogenetic studies that have contributed to elucidate neural circuit connectivity within the ventral tegmental area and the nucleus accumbens, two brain nuclei that are essential for the manifestation of addiction-related behaviors. Additional targeted manipulation of genetically defined neural populations in these brain regions, as well as afferent and efferent structures, promises to delineate the cellular mechanisms and circuit components required for the transition from natural goal-directed behavior to compulsive reward seeking despite negative consequences.

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Available from: Antonello Bonci, May 09, 2014
    • "The advent of optogenetics, which uses genetically encoded light-sensitive ion channels to selectively activate neurons of a defined brain region and neurotransmitter phenotype within physiological firing parameters, has overcome the limitations of previous techniques (e.g. electrical stimulation, pharmacological activation), transforming the neuroscience and depression fields (Albert, 2014;Nieh et al., 2013;Roeper, 2013;Stuber et al., 2012;Tye et al., 2013). In these studies, a virus containing the light-activated cation channel, channelrhodopsin2 (ChR2), which is driven by a cell type-selective promoter, is injected into a brain region of interest. "
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    ABSTRACT: Decades of research confirm that noradrenergic locus coeruleus (LC) neurons are essential for arousal, attention, motivation, and stress responses. While most studies on LC transmission focused unsurprisingly on norepinephrine (NE), adrenergic signaling cannot account for all the consequences of LC activation. Galanin coexists with NE in the vast majority of LC neurons, yet the precise function of this neuropeptide has proved to be surprisingly elusive given our solid understanding of the LC system. To elucidate the contribution of galanin to LC physiology, here we briefly summarize the nature of stimuli that drive LC activity from a neuroanatomical perspective. We go on to describe the LC pathways in which galanin most likely exerts its effects on behavior, with a focus on addiction, depression, epilepsy, stress, and Alzheimer's disease. We propose a model in which LC-derived galanin has two distinct functions: as a neuromodulator, primarily acting via the galanin 1 receptor (GAL1), and as a trophic factor, primarily acting via galanin receptor 2 (GAL2). Finally, we discuss how the recent advances in neuropeptide detection, optogenetics and chemical genetics, and galanin receptor pharmacology can be harnessed to identify the roles of LC-derived galanin definitively.
    No preview · Article · Nov 2015 · Brain research
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    • "Optogenetics has changed the landscape of neuroscience, and has enabled a new generation of experiments that dissect the causal roles of specific neural circuit components in normal and dysfunctional behavior. It has been used to increase our understanding of the neural circuits underlying mood disorders (Covington et al., 2010; Tye et al., 2011, 2013; Lobo et al., 2012; Warden et al., 2012; Kim et al., 2013; Lammel et al., 2014; Sidor et al., 2015), addiction (Lobo et al., 2010; Chen et al., 2013), Parkinson's disease (Gradinaru et al., 2009; Kravitz et al., 2010), obsessive compulsive disorder (Ahmari et al., 2013; Burguière et al., 2013), social behavior (Yizhar et al., 2011b; Yizhar, 2012; Dölen et al., 2013; Gunaydin et al., 2014), and reward (Tsai et al., 2009; Witten et al., 2010, 2011; Stuber et al., 2011a, 2011b; Van Zessen et al., 2012), among others (Deisseroth, 2014). The past decade has seen an explosion in the development of new optogenetic tools, both through discovery and engineering, and there is now a toolbox of exquisitely tuned opsins that can be used to stimulate and inhibit neural activity and control intracellular signaling cascades (Mattis et al., 2012; Tye and Deisseroth, 2012). "
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    ABSTRACT: This review, one of a series of articles, tries to make sense of optogenetics, a recently developed technology that can be used to control the activity of genetically defined neurons with light. Cells are first genetically engineered to express a light-sensitive opsin, which is typically an ion channel, pump, or G protein-coupled receptor. When engineered cells are then illuminated with light of the correct frequency, opsin-bound retinal undergoes a conformational change that leads to channel opening or pump activation, cell depolarization or hyperpolarization, and neural activation or silencing. Since the advent of optogenetics many different opsin variants have been discovered or engineered, and it is now possible to stimulate or inhibit neuronal activity or intracellular signaling pathways on fast or slow timescales with a variety of different wavelengths of light. Optogenetics has been successfully employed to enhance our understanding of the neural circuit dysfunction underlying mood disorders, addiction, and Parkinson's disease, and has enabled us to achieve a better understanding of the neural circuits mediating normal behavior. It has revolutionized the field of neuroscience, and has enabled a new generation of experiments that probe the causal roles of specific neural circuit components. © The Author 2015. Published by Oxford University Press on behalf of CINP.
    Full-text · Article · Jul 2015 · The International Journal of Neuropsychopharmacology
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    • "Thus, understanding the neural mechanisms supporting reward processing has been a long-­‐standing objective in neuroscience. Although considerable progress toward this objective has been made using a wide range of methodologies and approaches—including single-­‐unit neurophysiology (Hayden et al., 2009; Sugrue et al., 2005), optogenetics (Stuber et al., 2012), and brain stimulation (Amemori & Graybiel, 2012; Boggio et al., 2010)—this chapter will primarily focus on findings from human neuroimaging work. To investigate reward processing, researchers have employed concrete rewards such as money (Delgado et al., 2000; Knutson et al., 2001) and food (Kringelbach et al., 2003; Small et al., 2001), as well as more abstract rewards such as social status (Ly et al., 2011) and attractive faces (O'Doherty et al., 2003a; Winston et al., 2007). "
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    ABSTRACT: Our behavior is inextricably linked to rewards in our environment. This observation has sparked considerable interest in understanding the neural mechanisms that support reward processing in humans. Early neuroimaging studies implicated regions such as the striatum and ventromedial prefrontal cortex in reward processing, particularly how activation in these regions is modulated by anticipation and receipt of rewards. These findings have been extended in the context of models that account for the representation of subjective value, which influences decision making. Building from these findings, researchers are now beginning to characterize how social information has idiosyncratic influences on reward processing.
    Full-text · Chapter · Mar 2015
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