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
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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.
    The International Journal of Neuropsychopharmacology 07/2015; DOI:10.1093/ijnp/pyv079 · 4.01 Impact Factor
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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.
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    • "Although the bipolar stainless-steel electrodes were designed with a small exposed tip and stimulated with low intensity currents (25 µA) to increase target specificity, no further claim may be made as to whether passage fibers or other amygdaloidal subnuclei could also have been activated, thus yielding to increased variability. It is also important to highlight that different stimulation methodologies (e.g., optogenetics targeted at BLA cell bodies), considered much more specific in terms of neuronal activation, also lead to high variability in behavior outcome quantification (Stuber et al. 2012). The c-Fos mapping of the B-Paired group may also reflect the activation of substrates involved in an on-going process of extinction (Knapska et al. 2007); considering that the group was previously stimulated, on day 1, with the same µES pattern. "
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    ABSTRACT: Inputting information to the brain through direct electrical microstimulation must consider how underlying neural networks encode information. One unexplored possibility is that a single electrode delivering temporally coded stimuli, mimicking an asynchronous serial communication port to the brain, can trigger the emergence of different brain states. This work used a discriminative fear-conditioning paradigm in rodents in which 2 temporally coded microstimulation patterns were targeted at the amygdaloid complex. Each stimulus was a binary-coded “word” made up of 10 ms bins, with 1’s representing a single pulse stimulus: A-1001111001 and B-1110000111. During 3 consecutive retention tests (i.e., day-word: 1-B; 2-A, and 3-B), only binary coded words previously paired with a foot-electroshock elicited proper aversive behavior. To determine the neural substrates recruited by the different stimulation patterns, c-Fos expression was evaluated 90 min after the last retention test. Animals conditioned to word-B, after stimulation with word-B, demonstrated increased hypothalamic c-Fos staining. Animals conditioned to word-A, however, showed increased prefrontal c-Fos labeling. In addition, prefrontal-cortex and hypothalamic c-Fos staining for, respectively, word-B- and word-A-conditioned animals, was not different than that of an unpaired control group. Our results suggest that, depending on the valence acquired from previous learning, temporally coded microstimulation activates distinct neural networks and associated behavior.
    Cerebral Cortex 01/2015; 25. DOI:10.1093/cercor/bhu313 · 8.67 Impact Factor
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