The time constant of the decaying phase of gating currents was determined using a single or double time-exponential fitting procedure (see Figure S1). A weighted time constant was OSI906 calculated when a double exponential fit was used. The time constant of the activating (Nav and Kv) or deactivating (Nav) phases of ionic currents was determined using distinct monoexponential fits (see Figure S1). The V1/2 values were determined by fitting the Q-V curves with a two-state Boltzmann function. The statistical

analysis of the τmax values was performed using a standard two-tailed paired Student’s t test. All error bars indicate ±SEM. We thank Dr. Allan Drummond and Dr. Ramon Latorre for their insightful comments on the manuscript, Dr. Christopher Ahern and Dr. Stephan Pless for providing us with a plasmid encoding the human Nav1.5, and Dr. Ernesto Vargas for providing the pdb files for the all-atom simulation of the consensus resting state model. This work was

ALK mutation supported by National Institutes of Health grant GM030376. “
“Although amygdala circuitry has been implicated in anxiety in both humans (Büchel et al., 1999, Etkin et al., 2009 and Somerville et al., 2004) and rodent models (Adamec et al., 1999 and Davidson, 2002), the way in which it interacts with a distributed neural circuit to mediate anxiety is poorly understood. In rodents, a causal role for the amygdala microcircuitry has emerged in fear and anxiety (Ciocchi et al., 2010, Han

et al., 2009, Haubensak et al., 2010 and Tye et al., 2011), but relationships between the amygdala and distal regions are still unclear. One distal amygdalar projection target implicated in anxiety-related behaviors is the ventral hippocampus (vHPC; File and Gonzalez, 1996, McHugh et al., 2004 and Richardson et al., 2004). The vHPC shares robust reciprocal connections with the basolateral nucleus of the amygdala (BLA; O’Donnell and Grace, 1995 and Pikkarainen et al., 1999). Subsequent studies have concluded that the ventral, but not the dorsal, to hippocampus is required for the expression of anxiety-related behaviors in the elevated plus maze (EPM) and open-field test (OFT) (Bannerman et al., 2003, Kheirbek et al., 2013 and Kjelstrup et al., 2002). In vivo electrophysiology recordings have revealed neural correlates in the BLA and vHPC to anxiety-related behaviors, such as increased tonic firing in BLA (Wang et al., 2011) and increased theta-frequency synchrony between the vHPC and prefrontal cortex (PFC; Adhikari et al., 2010 and Adhikari et al., 2011). Although these studies establish neural correlates between anxiety-related behaviors and the BLA or vHPC during anxiety assays, the precise neural encoding dynamics of the BLA-vHPC projection are unknown.