Article

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: 8.93). 12/2011; 71(12):1061-7. DOI: 10.1016/j.biopsych.2011.11.010
Source: PubMed

ABSTRACT 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.

1 Bookmark
 · 
154 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The brain's remarkable capacity to generate cognition and behavior is mediated by an extraordinarily complex set of neural interactions that remain largely mysterious. This complexity poses a significant challenge in developing therapeutic interventions to ameliorate psychiatric disease. Accordingly, few new classes of drugs have been made available for patients with mental illness since the 1950s. Optogenetics offers the ability to selectively manipulate individual neural circuit elements that underlie disease-relevant behaviors and is currently accelerating the pace of preclinical research into neurobiological mechanisms of disease. In this review, we highlight recent findings from studies that employ optogenetic approaches to gain insight into normal and aberrant brain function relevant to mental illness. Emerging data from these efforts offers an exquisitely detailed picture of disease-relevant neural circuits in action, and hints at the potential of optogenetics to open up entirely new avenues in the treatment of psychiatric disorders.
    Current Opinion in Neurobiology 09/2014; 30C:9-16. DOI:10.1016/j.conb.2014.08.004 · 6.77 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A B S T R AC T : Elucidating the neuronal mechanisms underlying movement disorders is a major challenge because of the intricacy of the relevant neural circuits, which are characterized by diverse cell types and complex connectivity. A major limitation of traditional techniques, such as electrical stimulation or lesions, is that individual elements of a neural circuit cannot be selectively manipulated. Moreover, available treatments are largely based on trial and error rather than a detailed understanding of the circuit mechanisms. Gaps in our knowledge of the circuit mechanisms for movement disorders , as well as mechanisms underlying known treatments such as deep brain stimulation, make it difficult to design new and improved treatment options. In this perspective , we discuss how optogenetics, which allows researchers to use light to manipulate neuronal activity, can contribute to the understanding and treatment of movement disorders. We outline the advantages and limitations of optogenetics and discuss examples of studies that have used this tool to clarify the role of the basal ganglia circuitry in movement. V C 2014 International Par-kinson and Movement Disorder Society K e y Wo rd s : Channelrhodopsin; DBS; dystonia;
  • [Show abstract] [Hide abstract]
    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 · 8.31 Impact Factor

Full-text (3 Sources)

Download
48 Downloads
Available from
Jun 1, 2014