Reversible online control of habitual behavior by optogenetic perturbation of medial prefrontal cortex

McGovern Institute for Brain Research and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 10/2012; 109(46). DOI: 10.1073/pnas.1216264109
Source: PubMed


Habits tend to form slowly but, once formed, can have great stability. We probed these temporal characteristics of habitual behaviors by intervening optogenetically in forebrain habit circuits as rats performed well-ingrained habitual runs in a T-maze. We trained rats to perform a maze habit, confirmed the habitual behavior by devaluation tests, and then, during the maze runs (ca. 3 s), we disrupted population activity in a small region in the medial prefrontal cortex, the infralimbic cortex. In accordance with evidence that this region is necessary for the expression of habits, we found that this cortical disruption blocked habitual behavior. Notably, however, this blockade of habitual performance occurred on line, within an average of three trials (ca. 9 s of inhibition), and as soon as during the first trial (<3 s). During subsequent weeks of training, the rats acquired a new behavioral pattern. When we again imposed the same cortical perturbation, the rats regained the suppressed maze-running that typified the original habit, and, simultaneously, the more recently acquired habit was blocked. These online changes occurred within an average of two trials (ca. 6 s of infralimbic inhibition). Measured changes in generalized performance ability and motivation to consume reward were unaffected. This immediate toggling between breaking old habits and returning to them demonstrates that even semiautomatic behaviors are under cortical control and that this control occurs online, second by second. These temporal characteristics define a framework for uncovering cellular transitions between fixed and flexible behaviors, and corresponding disturbances in pathologies.

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    • "Animals continued goal-directed behavior when ILC pyramidal cells were optogenetically silenced during habit formation, but once the habit was fully expressed, photoinhibition evoked a new habitual pattern. Moreover, when photoinhibition was repeated during execution of the new habit, animals re-expressed the original habit (Smith et al., 2012). This immediate switching between habitual behaviors demonstrates that even semiautomatic behaviors are under cortical control while they are being performed. "
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    ABSTRACT: The medial prefrontal cortex (mPFC) is critically involved in numerous cognitive functions, including attention, inhibitory control, habit formation, working memory and long-term memory. Moreover, through its dense interconnectivity with subcortical regions (e.g., thalamus, striatum, amygdala and hippocampus), the mPFC is thought to exert top-down executive control over the processing of aversive and appetitive stimuli. Because the mPFC has been implicated in the processing of a wide range of cognitive and emotional stimuli, it is thought to function as a central hub in the brain circuitry mediating symptoms of psychiatric disorders. New optogenetics technology enables anatomical and functional dissection of mPFC circuitry with unprecedented spatial and temporal resolution. This provides important novel insights in the contribution of specific neuronal subpopulations and their connectivity to mPFC function in health and disease states. In this review, we present the current knowledge obtained with optogenetic methods concerning mPFC function and dysfunction and integrate this with findings from traditional intervention approaches used to investigate the mPFC circuitry in animal models of cognitive processing and psychiatric disorders.
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    • "The many output connections of IL cortex could support the translation of this general function into different behavioral effects in different situations (Peters et al., 2009). Our finding that IL inhibition could both block and reinstate a particular habit certainly suggests some form of dependency of IL function on context or history (Smith et al., 2012). "
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    ABSTRACT: Understanding habits at a biological level requires a combination of behavioral observations and measures of ongoing neural activity. Theoretical frameworks as well as definitions of habitual behaviors emerging from classic behavioral research have been enriched by new approaches taking account of the identification of brain regions and circuits related to habitual behavior. Together, this combination of experimental and theoretical work has provided key insights into how brain circuits underlying action-learning and action-selection are organized, and how a balance between behavioral flexibility and fixity is achieved. New methods to monitor and manipulate neural activity in real time are allowing us to have a first look "under the hood" of a habit as it is formed and expressed. Here we discuss ideas emerging from such approaches. We pay special attention to the unexpected findings that have arisen from our own experiments suggesting that habitual behaviors likely require the simultaneous activity of multiple distinct components, or operators, seen as responsible for the contrasting dynamics of neural activity in both cortico-limbic and sensorimotor circuits recorded concurrently during different stages of habit learning. The neural dynamics identified thus far do not fully meet expectations derived from traditional models of the structure of habits, and the behavioral measures of habits that we have made also are not fully aligned with these models. We explore these new clues as opportunities to refine an understanding of habits.
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    • "However , rats that have been over trained in this task continue to lever-press following devaluation of the food reward, indicating habitual behavior. Neural inactivation of the infralimbic cortex reinstates goal-directed behavior in overtrained rats, whereas neural inactivation of the prelimbic cortex leads to habitual behavior in rats that have received comparatively less training (Coutureau and Killcross, 2003; Killcross and Coutureau, 2003; Haddon and Killcross, 2011; Smith et al., 2012). Taken together, whereas both regions appear to be required for switching strategies, the infralimbic and prelimbic subregions appear to be selectively involved in the expression of habitual and goal-directed behaviors , respectively. "
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