Our use of the same context for conditioning and extinction prevented the rat from using context to disambiguate the meaning of the extinguished cue. Under such conditions, hippocampal activity is known to be required to disambiguate cues (Bouton, 2002; Tsetsenis et al., 2007), and prefrontal activity is required to switch between memory strategies (Rich

and Shapiro, 2009) and select between conflicting motivations (Granon and Changeux, 2012). Individuals suffering from mood and anxiety disorders tend to interpret ambiguous situations as threatening, leading to a state Selleck Talazoparib of hypervigilance. Individuals with high anxiety (Kim et al., 2011) or PTSD (Milad et al., 2009) show hyperactivity in the dorsal anterior cingulate cortex (dACC), a homolog of rodent PL (Milad et al., 2007). Consistent with the inhibitory function of vHPC we describe, Selleckchem Selisistat emotional disorders associated with heightened vigilance, such as PTSD, depression, and schizophrenia, are all accompanied by a reduction in the volume of the anterior hippocampus (Bremner et al., 2000; Gilbertson et al., 2002; McCarley et al., 1999), a homolog of rodent vHPC. This is consistent with the notion that the hippocampus

is necessary to keep fear and vigilance under control (Tsetsenis et al., 2007). Notably, in PTSD, increased activity in dACC is correlated with decreased activity in the anterior hippocampus (Milad et al., 2009). Thus, deficient hippocampal inhibition of the prefrontal cortex may put

individuals at risk for anxiety disorders (Shin et al., 2009) and may even constitute a premorbid risk factor (Linnman et al., 2012). Targeting the hippocampal-dACC gating circuit, heptaminol for example with transcranial magnetic stimulation or methods to promote neurogenesis in the anterior hippocampus (Sahay and Hen, 2007), may help treat a wide range of disorders characterized by deficits in emotional regulation. Male Sprague-Dawley rats (Harlan Laboratories, Indianapolis, IN) weighing 270–320 g were individually housed and handled as described previously (Burgos-Robles et al., 2009; Sierra-Mercado et al., 2011). Food was restricted to 18 g/day of standard laboratory rat chow until rats reached 85% of their free-feeding weight. Rats were trained to press a bar for food on a variable interval schedule of reinforcement (VI-60). Pressing maintains a constant level of activity against which freezing could be reliably measured, and provides a measure of moderate levels of fear (Mast et al., 1982; Sierra-Mercado et al., 2011). All procedures were approved by the Institutional Animal Care and Use Committee of the University of Puerto Rico School of Medicine in compliance with the National Institutes of Health guidelines for the care and use of laboratory animals.