NEUROFEAR · Neuronal circuits controlling fear behavior

Accurate adaptation to stimuli predicting threatening outcome is critical to survival. An insufficient fear reaction may lead the animal to overlook future signs of danger, whereas overreacting may lead the animal to failure to explore and miss opportunities for feeding or mating. Numerous data indicate that the medial prefrontal cortex (mPFC) plays a key role in the control of fear behavior and that distinct prefrontal areas differentially regulate the expression/inhibition of fear responses. Whereas lesions/inactivations of the mPFC infralimbic (IL) area promote fear expression, lesions/inactivations of the mPFC prelimbic area (PL) promote fear inhibition. Moreover, PL and IL receive segregated inputs from functionally distinct amygdala circuits activated during high and low fear states. These data suggest that a key function of mPFC circuits might be to integrate inputs from the amygdala to ultimately gate fear expression via projections to specific neuronal circuits. However, little is known about the underlying neuronal circuits. Is the rapid switch between expression/suppression of fear behaviors mediated by the same circuits or does the mPFC contain distinct circuits dedicated to the control of opposite behaviors? Is there an organization in terms of afferents and efferent at the level of mPFC neuronal circuits? To address these questions we will use a cross-level approach combining in vivo electrophysiological optogenetic and behavioral approaches to elucidate the anatomical/physiological properties of mPFC circuits and to address their functional role in the control of fear behavior. We will first examine the activation and connectivity of mPFC circuits using in vivo extracellular recordings and extracellular stimulations. We will next selectively manipulate these circuits during behavior using light-activated proteins to establish causal relationships. Finally we will study their plasticity and anatomical properties using in vivo intracellular recordings.