Optogenetic inhibition of cocaine seeking in rats

Stefanik, Michael T.; Moussawi, Khaled; Kupchik, Yonatan M.; Smith, Kyle C.; Miller, Rachel L.; Huff, Mary L.; Deisseroth, Karl; Kalivas, Peter W.; LaLumiere, Ryan T.

doi:10.1111/j.1369-1600.2012.00479.x

Cited by 223 publications

(213 citation statements)

References 6 publications

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“…Thus, optogenetic tools may be utilized to study the effects of specific ions on specific physiological processes. If side effects from the ions conducted by specific opsins are a concern, one useful strategy is to use multiple opsins that result in similar voltage effects, but rely on different ionic species (Adesnik et al 2012;Stefanik et al 2012;Kimura et al 2013). …”

Section: Channel and Pump Activitymentioning

confidence: 99%

Principles of designing interpretable optogenetic behavior experiments

2015

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Over the last decade, there has been much excitement about the use of optogenetic tools to test whether specific cells, regions, and projection pathways are necessary or sufficient for initiating, sustaining, or altering behavior. However, the use of such tools can result in side effects that can complicate experimental design or interpretation. The presence of optogenetic proteins in cells, the effects of heat and light, and the activity of specific ions conducted by optogenetic proteins can result in cellular side effects. At the network level, activation or silencing of defined neural populations can alter the physiology of local or distant circuits, sometimes in undesired ways. We discuss how, in order to design interpretable behavioral experiments using optogenetics, one can understand, and control for, these potential confounds.

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Section: Channel and Pump Activitymentioning

confidence: 99%

Principles of designing interpretable optogenetic behavior experiments

2015

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“…Verification of optic probes' placement was performed with a standard Nissl stain preparation (Cresyl violet) and light microscopy according to the Paxinos and Watson atlas (2005). Expression in the cell bodies and axons in the VH was verified using immunohistochemistry procedures, as described previously Stefanik et al 2013). GFP/ eYFP expression was assessed using a light microscope.…”

Section: Verification Of Opsin Expression and Histologymentioning

confidence: 99%

Basolateral amygdala projections to ventral hippocampus modulate the consolidation of footshock, but not contextual, learning in rats

et al. 2016

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The basolateral amygdala (BLA) modulates memory consolidation for a variety of types of learning, whereas other brain regions play more selective roles in specific kinds of learning suggesting a role for differential consolidation via distinct BLA pathways. The ventral hippocampus (VH), an efferent target of the BLA, has been suggested to selectively process emotionrelated learning, yet whether the BLA VH pathway modulates memory consolidation, and does so in a learning-specific manner, is unknown. To address this issue, the BLA of male Sprague-Dawley rats was bilaterally transduced to express either ChR2(E123A) or eArchT3.0. Fiber optic probes were implanted in the VH to provide illumination of BLA axons. Rats then underwent a modified contextual fear conditioning task permitting separation of context and footshock learning. On day 1, rats received 3 min of pre-exposure to the apparatus. On day 2, rats were placed into the apparatus, received an immediate footshock, and quickly removed. Retention was tested on day 4. Optical stimulation of the BLA VH pathway following footshock, but not context, training using trains of 40-Hz light pulses enhanced retention. Continuous optical inhibition of this pathway for 15 min starting 25 min after footshock training impaired retention. These findings indicate that BLA VH projections influence the consolidation for footshock, but not context, learning of a modified CFC task and provide direct evidence that BLA projections to other brain regions modulate memory consolidation selectively depending on the kind of learning involved.Learning and memory involves complex interactions among multiple brain regions that play discrete roles in the consolidation of specific kinds of memories. However, work strongly indicates that the basolateral amygdala (BLA) modulates the consolidation of a wide array of memories. It has been hypothesized that the BLA plays this more general role, at least in part, through interactions with distinct regions (McGaugh 2002(McGaugh , 2004McIntyre et al. 2012). BLA connections with forebrain regions such as the hippocampus and striatum that are selectively involved in the consolidation of certain kinds of memories (McDonald 1991;Pitkänen et al. 2000;McGaugh 2002;Malin and McGaugh 2006;Paz et al. 2006;Chavez et al. 2013) suggest that efferent pathways from the BLA may be selectively involved in modulating consolidation for specific kinds of information.Indeed, much evidence suggests that the BLA interacts with the hippocampus during memory consolidation (Packard et al. 1994;Roozendaal et al. 1999;Malin and McGaugh 2006) and that the BLA directly or indirectly influences activity and plasticity in different parts of the hippocampal formation (Ikegaya et al. 1995;Frey et al. 2001;McIntyre et al. 2005;McReynolds et al. 2014;Lovitz and Thompson 2015). These findings suggest pathway mechanisms by which the BLA influences the consolidation of memories regulated by the hippocampal formation. However, the hippocampus comprises different subregions, including dors...

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“…Preclinical studies, eg, have demonstrated that optogenetic modulation of these mesolimbic and mesocortical circuits can modulate drug-taking behavior in a causal manner (Chen et al, 2013c;Stefanik et al, 2013). Clinical studies are now investigating repetitive TMS (rTMS) as a tool to change drug-craving and drug-taking behavior.…”

Section: Implications For Treatment Development-dorsal Medial and Latmentioning

confidence: 99%

Mobilization of Medial and Lateral Frontal-Striatal Circuits in Cocaine Users and Controls: An Interleaved TMS/BOLD Functional Connectivity Study

Hanlon

Dowdle

Moss

et al. 2016

Neuropsychopharmacol

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The integrity of frontal-striatal circuits is an area of great interest in substance dependence literature, particularly as the field begins to develop neural circuit-specific brain stimulation treatments for these individuals. Prior research indicates that frontal-striatal connectivity is disrupted in chronic cocaine users in a baseline (resting) state. It is unclear, however, if this is also true when these circuits are mobilized by an external source. In this study, we measured the functional and structural integrity of frontal-striatal circuitry involved in limbic arousal and executive control in 36 individuals-18 cocaine-dependent individuals with a history of failed quit attempts and 18 age-matched controls. This was achieved by applying a transcranial magnetic stimulation to the medial prefrontal cortex (Brodmann area 10) and the dorsolateral prefrontal cortex (lateral Brodmann 9) while participants rested in the MRI scanner (TMS/BOLD imaging). Relative to the controls, cocaine users had a lower ventral striatal BOLD response to MPFC stimulation. The dorsal striatal BOLD response to DLPFC stimulation however was not significantly different between the groups. Among controls, DLPFC stimulation led to a reciprocal attenuation of MPFC activity (BA 10), but this pattern did not exist in cocaine users. No relationship was found between regional diffusion metrics and functional activity. Considered together these data suggest that, when engaged, cocaine users can mobilize their executive control system similar to controls, but that the 'set point' for mobilizing their limbic arousal system has been elevated-an interpretation consistent with opponent process theories of addiction.

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Optogenetic inhibition of cocaine seeking in rats

Cited by 223 publications

References 6 publications

Principles of designing interpretable optogenetic behavior experiments

Principles of designing interpretable optogenetic behavior experiments

Basolateral amygdala projections to ventral hippocampus modulate the consolidation of footshock, but not contextual, learning in rats

Mobilization of Medial and Lateral Frontal-Striatal Circuits in Cocaine Users and Controls: An Interleaved TMS/BOLD Functional Connectivity Study

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