Optogenetic Activation of the Infralimbic Cortex Suppresses the Return of Appetitive Pavlovian-Conditioned Responding Following Extinction

Villaruel, Franz R.; Lacroix, Franca; Sanio, Christian; Sparks, Daniel W.; Chapman, C. Andrew; Chaudhri, Nadia

doi:10.1093/cercor/bhx275

Cited by 34 publications

(41 citation statements)

References 41 publications

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“…With the rapid and widespread adoption of lightinducible technologies in neurobiology (Rost et al, 2017), these results provide a path forward when using these techniques in vitro. Recent reports have documented light-induced gene expression alterations of Fos in vivo (Villaruel et al, 2018), which may be the result of a similar stress response from poor heat dissipation during extended exposure times in vivo (Owen et al, 2019). In sum, our study highlights the importance of experimental design when using photoactivatable and imaging technologies.…”

Section: A B Csupporting

confidence: 60%

Blue Light-Induced Gene Expression Alterations in Cultured Neurons Are the Result of Phototoxic Interactions with Neuronal Culture Media

Duke

Savell

Tuscher

et al. 2019

eNeuro

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Blue wavelength light is used as an optical actuator in numerous optogenetic technologies employed in neuronal systems. However, the potential side effects of blue light in neurons has not been thoroughly explored, and recent reports suggest that neuronal exposure to blue light can induce transcriptional alterations in vitro and in vivo. Here, we examined the effects of blue wavelength light in cultured primary rat cortical cells. Exposure to blue light (470 nm) resulted in upregulation of several immediate early genes (IEGs) traditionally used as markers of neuronal activity, including Fos and Fosb, but did not alter the expression of circadian clock genes Bmal1, Cry1, Cry2, Clock, or Per2. IEG expression was increased following 4 h of 5% duty cycle light exposure, and IEG induction was not dependent on light pulse width. Elevated levels of blue light exposure induced a loss of cell viability in vitro, suggestive of overt phototoxicity. Induction of IEGs by blue light was maintained in cortical cultures treated with AraC to block glial proliferation, indicating that induction occurred selectively in postmitotic neurons. Importantly, changes in gene expression induced by blue wavelength light were prevented when cultures were maintained in a photoinert media supplemented with a photostable neuronal supplement instead of commonly utilized neuronal culture media and supplements. Together, these findings suggest that light-induced gene expression alterations observed in vitro stem from a phototoxic interaction between commonly used media and neurons, and offer a solution to prevent this toxicity when using photoactivatable technology in vitro.

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Section: A B Csupporting

confidence: 60%

Blue Light-Induced Gene Expression Alterations in Cultured Neurons Are the Result of Phototoxic Interactions with Neuronal Culture Media

Duke

Savell

Tuscher

et al. 2019

eNeuro

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“…Using this task, we previously reported selective ABA renewal of responding to an alcohol-predictive CS+ (Chaudhri et al, 2008b) that was dependent on dopaminergic (Sciascia et al, 2014) and cholinergic neurotransmission (Lacroix et al, 2017). We also reported ABA renewal of responding to a CS+ that predicted sucrose (Chaudhri et al, 2008b) and a reduction of this effect by optogenetic activation of the infralimbic prefrontal cortex during the CS (Villaruel et al, 2018). Given that ABA renewal is a reliable phenomenon across learning paradigms, we predicted that a return to the conditioning context following extinction in a different context would selectively renew CS+ responding in both alcohol-and sucrose-trained rats.…”

Section: Introductionmentioning

confidence: 89%

Comparing ABA, AAB, and ABC Renewal of Appetitive Pavlovian Conditioned Responding in Alcohol- and Sucrose-Trained Male Rats

Khoo

Sciascia

Brown

et al. 2020

Front. Behav. Neurosci.

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Conditioned responding can be renewed by re-exposure to the conditioning context following extinction in a different context (ABA renewal) or by removal from the extinction context (AAB or ABC renewal). ABA renewal is robust in Pavlovian and operant conditioning paradigms. However, fewer studies have investigated AAB and ABC renewal of appetitive conditioning, and those that did predominantly used operant conditioning tasks. Renewal has theoretical relevance for extinction and for exposurebased treatments for substance use disorders that aim to extinguish reactivity to drug-predictive cues. We therefore investigated ABA, AAB, and ABC renewal of Pavlovian conditioned responding to cues that predicted either alcohol or sucrose. Male, Long-Evans rats (Charles River) were exposed to either 15% ethanol (Study 1: "alcohol") or 10% sucrose (Study 2: "sucrose") in their home cages. Next, they were trained to discriminate between two auditory stimuli (white noise and clicker; 10 s) in conditioning chambers equipped with distinct olfactory, visual, and tactile contextual stimuli (context A). One conditioned stimulus (CS+) was paired with fluid delivery (0.2 ml/CS+; 3.2 ml/session; alcohol or sucrose in separate experiments), and the second CS (CS−) was not. In all sessions (conditioning, extinction, and test), each CS was presented 16 times/session on a variable-time 67-s schedule, and entries into the fluid port were recorded. CS+ port entries were then extinguished by withholding fluid delivery either in context A or in a second, different context (context B). Next, we assessed ABA, AAB, and ABC renewal in the absence of fluid delivery. During extinction, CS+ port entries were initially elevated in context A relative to context B. ABA renewal of CS+ port entries occurred in both alcohol-and sucrose-trained rats. ABC renewal approached statistical significance when data from both experiments were combined. No AAB renewal was observed, and, in fact, alcohol-trained rats showed AAB suppression. These results corroborate the reliability of ABA renewal and suggest that ABC renewal is a modest effect that may require greater statistical power to detect. From a treatment perspective, the lack of AAB renewal suggests that exposure-based treatments for substance use disorders might benefit from implementation in real-world, drug-use contexts.

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“…The function of IL is important for the expression of auditory-triggered conditioned fear in situations of latent inhibition. If IL is inhibited (e.g., infusion of GABAergic agonist, or activation of inhibitory M4 DREADD) the 'extinction' or outcome-specific inhibition disappears and the extinct behavior is reinstated (Do-Monte et al, 2015;Laurent et al, 2016) and if IL is stimulated (e.g., ChR2 or GABAergic antagonist) the extinction is strengthen (Do-Monte et al, 2015;Lingawi et al, 2018) and attenuation of responses to the conditioned stimulus is observed (Villaruel et al, 2018). Following a slightly different approach Halladay & Blair (2017) demonstrated that bilateral IL inactivation (GABAergic agonist) increases freezing responses and conditioned motor inhibition, whereas bilateral activation (GABAergic antagonist) enhances conditioned motor activation (turning away from an anticipated eyelid shock).…”

Section: Prelimbic (Prl) and Infralimbic (Il) Prefrontal Corticesmentioning

confidence: 99%

Thalamic afferents to prefrontal cortices from ventral motor nuclei in decision‐making

Sieveritz

García‐Muñoz

Arbuthnott

2018

Eur J of Neuroscience

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The focus of this literature review is on the three interacting brain areas that participate in decision‐making: basal ganglia, ventral motor thalamic nuclei, and medial prefrontal cortex, with an emphasis on the participation of the ventromedial and ventral anterior motor thalamic nuclei in prefrontal cortical function. Apart from a defining input from the mediodorsal thalamus, the prefrontal cortex receives inputs from ventral motor thalamic nuclei that combine to mediate typical prefrontal functions such as associative learning, action selection, and decision‐making. Motor, somatosensory and medial prefrontal cortices are mainly contacted in layer 1 by the ventral motor thalamic nuclei and in layer 3 by thalamocortical input from mediodorsal thalamus. We will review anatomical, electrophysiological, and behavioral evidence for the proposed participation of ventral motor thalamic nuclei and medial prefrontal cortex in rat and mouse motor decision‐making.

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Optogenetic Activation of the Infralimbic Cortex Suppresses the Return of Appetitive Pavlovian-Conditioned Responding Following Extinction

Cited by 34 publications

References 41 publications

Blue Light-Induced Gene Expression Alterations in Cultured Neurons Are the Result of Phototoxic Interactions with Neuronal Culture Media

Blue Light-Induced Gene Expression Alterations in Cultured Neurons Are the Result of Phototoxic Interactions with Neuronal Culture Media

Comparing ABA, AAB, and ABC Renewal of Appetitive Pavlovian Conditioned Responding in Alcohol- and Sucrose-Trained Male Rats

Thalamic afferents to prefrontal cortices from ventral motor nuclei in decision‐making

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