F the amygdala (Webster et al., 1991; Baizer et al., 1993; Cheng et al., 1997; Ghashghaei and Barbas, 2002; Stefanacci and Amaral, 2002; Freese and Amaral, 2005), the lateral OFC (lOFC) (Webster et al., 1994; Kondo et al., 2003; Barbas, 2007) along with the frontal eye fields (FEF) inside the PFC (Webster et al., 1994; Schall et al., 1995). TE and to a lesser extent TEO also projects to vlPFC, even though the function is just not however clear (Webster et al., 1994; Saleem et al., 2008; Gerbella et al., 2010) and may perhaps involve auditory processing (Medalla and Barbas, 2014). The OFC is a highly interconnected area within the primate brain, with connections amongst sensory and prefrontal cortices too as limbic structures, including bidirectional connections together with the amygdala (Carmichael and Price tag, 1995; Rolls, 2005; Barbas, 2007; Cost, 2007; Cho et al., 2013; Timbie and Barbas, 2014). Though the amygdala learns about emotional and fearful stimuli, the OFC does this at the same time, whilst also computing a punishment or reward value (Rolls, 2004; Dolan, 2007; Rolls and Grabenhorst, 2008). The OFC is generally divided into lateralmedial and anteriorposterior divisions. The lOFC receives visual stimuli from IT and other sensory places, with all the strongest visual projections from TE (Webster et al., 1994; Kondo et al., 2003; Barbas, 2007), likely over the uncinate fasciculus (UF). The lOFCFrontiers in Systems Neuroscience www.frontiersin.orgAugust 2015 Volume 9 ArticleSilverstein and IngvarFear signaling pathwaysis believed to be more active when processing aversive stimuli, although the medial OFC (mOFC) is more active when processing reward (O’Doherty et al., 2001; Kringelbach and Rolls, 2004). Learned punishments (or fears) and rewards are conditioned responses or secondary reinforcers from unconditioned stimuli or key reinforcers (LeDoux, 1996; Rolls, 2005). The mOFC projects to the nucleus accumbens (NAcc) and probably stimulates it on expected reward. Along the anteriorposterior axis, easier reinforcers are represented in the posterior location and grow to be progressively more complex toward the anterior (Kringelbach, 2005). The posterior OFC PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/21376593 (pOFC) has the strongest connections using the amygdala (Barbas, 2007; Barbas et al., 2011; Timbie and Barbas, 2014), with unidirectional projections from the pOFC towards the ITC and bidirectional projections MedChemExpress Maytansinoid DM1 involving the pOFC and the B and AB nuclei. The pOFC also receives inputs from sensory and olfactory cortices. Whilst anatomical studies show robust pOFC connectivity, functional imaging research ordinarily have distinguished only among lOFC and mOFC (Kahnt et al., 2012), so it really is assumed that pOFC and mOFC functional activity are blended together. Projections from other areas on the OFC also innervate the basal, AB, Ce, LA nuclei and ITC inside the amygdala, even though projections back to OFC originate in the basal, AB and LA nuclei. The PFC is a large cortical area attributed to many functions in executive handle. Along the medial-lateral axis, processing is self-referential to situational, along the ventral-dorsal axis, processing is emotional to cognitive and along the posterioranterior axis, processing is extra visceral to abstract. The PFC is typically divided into numerous regions, 3 of that will be focused on here. These are the medial PFC (mPFC), dorsolateral PFC (dlPFC) and the ventrolateral PFC (vlPFC). Activity inside the mPFC has been correlated with self-referential processing (Gusnard et al., 2001) and extinction, although situational proc.