Representation of Spatial Goals in Rat Orbitofrontal Cortex

Feierstein, Claudia E.; Quirk, Michael C.; Uchida, Naoshige; Sosulski, Dara L.; Mainen, Zachary F.

doi:10.1016/j.neuron.2006.06.032

Cited by 244 publications

(313 citation statements)

References 67 publications

(114 reference statements)

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“…Specifically, chronic oPFC GABA A a1 silencing impairs the performance of goal-directed response strategies, while M2 GABA A a1 inhibition enhances sensitivity to action-outcome relationships. The effects of oPFC GABA A a1 knockdown are context selective, consistent with evidence that spatial information is represented within the ventrolateral oPFC during appetitive choice tasks (Feierstein et al, 2006), and that the oPFC regulates behavioral sensitivity to rewardassociated contextual cues (Lasseter et al, 2009(Lasseter et al, , 2014.…”

Section: Introductionsupporting

confidence: 71%

“…In addition, glutamatergic projections from the cortex and dopamine input from the ventral tegmental area converge on dendritic spines within the rodent nucleus accumbens (Bouyer et al, 1984); the targeted medium spiny neurons may then coordinate information being shuttled to the basal ganglia to regulate the expression of instrumental decisionmaking strategies or habits, depending on an animal's drug, stress, or training history. In addition, oPFC neurons, particularly within the ventrolateral region affected here, encode information regarding space, context, and motor requirements as they pertain to acquiring a reinforcer (Feierstein et al, 2006). All of these functions could be degraded by chronic oPFC GABA A a1 silencing and associated molecular sequelae.…”

Section: Regulation Of Action Selection By the Opfcmentioning

confidence: 88%

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GABAAα1-Mediated Plasticity in the Orbitofrontal Cortex Regulates Context-Dependent Action Selection

Swanson

Allen

Shapiro³

et al. 2014

Neuropsychopharmacol

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An essential aspect of goal-directed action selection is differentiating between behaviors that are more, or less, likely to be reinforced. Habits, by contrast, are stimulus-elicited behaviors insensitive to action-outcome contingencies and are considered an etiological factor in several neuropsychiatric disorders. Thus, isolating the neuroanatomy and neurobiology of goal-directed action selection on the one hand, and habit formation on the other, is critical. Using in vivo viral-mediated gene silencing, we knocked down Gabra1 in the orbitofrontal prefrontal cortex (oPFC) in mice, decreasing oPFC GABA A a1 expression, as well as expression of the synaptic marker PSD-95. Mice expressing Green Fluorescent Protein or Gabra1 knockdown in the adjacent M2 motor cortex served as comparison groups. Using instrumental response training followed by action-outcome contingency degradation, we then found that oPFC GABA A a1 deficiency impaired animals' ability to differentiate between actions that were more or less likely to be reinforced, though sensitivity to outcome devaluation and extinction were intact. Meanwhile, M2 GABA A a1 deficiency enhanced sensitivity to action-outcome relationships. Behavioral abnormalities following oPFC GABA A a1 knockdown were rescued by testing mice in a distinct context relative to that in which they had been initially trained. Together, our findings corroborate evidence that chronic GABA A a1 deficiency remodels cortical synapses and suggest that neuroplasticity within the healthy oPFC gates the influence of reward-related contextual stimuli. These stimuli might otherwise promote maladaptive habit-based behavioral response strategies that contribute to-or exacerbateneuropsychiatric illness.

show abstract

Section: Introductionsupporting

confidence: 71%

Section: Regulation Of Action Selection By the Opfcmentioning

confidence: 88%

GABAAα1-Mediated Plasticity in the Orbitofrontal Cortex Regulates Context-Dependent Action Selection

Swanson

Allen

Shapiro³

et al. 2014

Neuropsychopharmacol

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“…Although at least one previous report has implicated the OFC in conditioned reinforcement 8 , our results indicate that its role may be entirely subordinate to this region's well-documented involvement in signalling expected outcomes (see Supplementary Discussion for consideration of alternative interpretation involving attention). The OFC is activated by cues and during responding in a way that seems to reflect features of the specific outcomes that are to follow-particularly their value [10][11][12][13][14][15][16] -and damage to the OFC has been shown to impair changes in cue-evoked responding after devaluation [17][18][19] . Here we show that the OFC is also critical for instrumental responding when that responding is driven by cue-evoked representations of expected outcomes.…”

mentioning

confidence: 99%

The role of the orbitofrontal cortex in the pursuit of happiness and more specific rewards

Burke

Franz

Miller

et al. 2008

Nature

158

143

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Cues that reliably predict rewards trigger the thoughts and emotions normally evoked by those rewards. Humans and other animals will work, often quite hard, for these cues. This is termed conditioned reinforcement. The ability to use conditioned reinforcers to guide our behaviour is normally beneficial; however, it can go awry. For example, corporate icons, such as McDonald's Golden Arches, influence consumer behaviour in powerful and sometimes surprising ways 1 , and drug-associated cues trigger relapse to drug seeking in addicts and animals exposed to addictive drugs, even after abstinence or extinction 2,3 . Yet, despite their prevalence, it is not known how conditioned reinforcers control human or other animal behaviour. One possibility is that they act through the use of the specific rewards they predict; alternatively, they could control behaviour directly by activating emotions that are independent of any specific reward. In other words, the Golden Arches may drive business because they evoke thoughts of hamburgers and fries, or instead, may be effective because they also evoke feelings of hunger or happiness. Moreover, different brain circuits could support conditioned reinforcement mediated by thoughts of specific outcomes versus more general affective information. Here we have attempted to address these questions in rats. Rats were trained to learn that different cues predicted different rewards using specialized conditioning procedures that controlled whether the cues evoked thoughts of specific outcomes or general affective representations common to different outcomes. Subsequently, these rats were given the opportunity to press levers to obtain short and otherwise unrewarded presentations of these cues. We found that rats were willing to work for cues that evoked either outcome-specific or general affective representations. Furthermore the orbitofrontal cortex, a prefrontal region important for adaptive decision-making 4 , was critical for the former but not for the latter form of conditioned reinforcement.

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“…The OFC, for example, receives olfactory input from the piriform cortex, and neurons of the OFC detect and discriminate among odors (Rolls and Baylis, 1994;Lipton et al, 1999), represent learned associations between odors and location (Lipton et al, 1999), and encode rewards and punishments associated with odors (Schoenbaum et al, 1998). These findings indicate that the OFC acts both as a secondary olfactory cortex and a higher order association cortex (Lipton et al, 1999;Feierstein et al, 2006;Roesch et al, 2006). It was therefore critical to discriminate between egr-2 induction that occurred in response to odor exposure alone and induction that occurred in response to ASST-test exposure (i.e., stimulus-modality-independent).…”

mentioning

confidence: 99%

Induction of early growth response gene 2 expression in the forebrain of mice performing an attention-set-shifting task

DeSteno

Schmauss

2008

Neuroscience

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Early growth response (egr) genes encode transcription factors that are induced by stimuli that cause synaptic plasticity. Here we show that the expression of one member of this family, egr-2, is induced in the orbital frontal cortex (OFC) and medial prefrontal cortex (mPFC) of mice performing an attention-set-shifting task (ASST). The ASST is a series of two-choice perceptual discriminations between different odors and textures. Within the OFC and mPFC, different subregions exhibited egr-2 induction in response to different test-related features. In the medial OFC and the anterior cingulate subregion of the mPFC, egr-2 induction occurred in response to exposure to the novel odor stimulus. In the ventrolateral OFC and the pre-and infralimbic mPFC, additional egr-2 induction occurred during the associative learning phase of the ASST. In the infralimbic mPFC, further egr-2 induction occurred when mice performed set-shifting and reversal learning phases of the ASST. Mice with enhanced set-shifting performance exhibited decreased egr-2 induction in the mPFC indicating that the magnitude of egr-2 induction correlates with the magnitude of attentional demand. This decrease was largest in the infralimbic mPFC suggesting further that egr-2 induction in this region plays a role in the attentional control during set-shifting.In contrast to egr-2, neither egr-1 nor egr-3 expression was altered in ASST-tested mice, and no egr-2 induction occurred in mice that performed a spatial working memory task. These findings suggest a specific role of egr-2-mediated transcriptional activation in cognitive functions associated with attention. Keywordsearly growth response gene; medial prefrontal cortex; orbital frontal cortex; attention; working memory; miceThe earliest genomic response to synaptic activity is the induction of expression of immediate early genes (IEGs) encoding transcription factors that participate in synaptic and structural neuronal responses to external stimulation. Although induction of expression of the IEG c- ., Email address: cs581@columbia.edu (C. Schmauss). Section Editor: Dr. Werner Sieghart (Molecular Neuroscience) Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2008 April 21. Published in final edited form as:Neuroscience. 2008 March 18; 152(2): 417-428. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscriptfos is a powerful tool to map the activation of neuronal pathways (Sagar et al, 1988), the identification of other IEG transcription factors is critical...

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Representation of Spatial Goals in Rat Orbitofrontal Cortex

Cited by 244 publications

References 67 publications

GABAAα1-Mediated Plasticity in the Orbitofrontal Cortex Regulates Context-Dependent Action Selection

GABAAα1-Mediated Plasticity in the Orbitofrontal Cortex Regulates Context-Dependent Action Selection

The role of the orbitofrontal cortex in the pursuit of happiness and more specific rewards

Induction of early growth response gene 2 expression in the forebrain of mice performing an attention-set-shifting task

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