A traumatic emotional experience inducing a lifelong anxiety disorder would be one possibility. Evidence implicating Selleckchem Olaparib TrkB signaling in the

induction of contextual fear conditioning (Rattiner et al., 2004), an animal model mimicking some features of posttraumatic stress disorder, supports this idea. The nature of the cellular consequences of enhanced TrkB activation that underlies the pathological consequences of the brief epoch of SE is presently unclear. Determining the cellular and subcellular locale of the activated TrkB is a critical first step to elucidating the cellular consequences, a determination that can be made using high-resolution microscopy methods to localize pTrkB (Helgager et al., 2013). The present findings provide proof of concept evidence that activation of TrkB kinase is required for the induction of chronic, recurrent seizures and anxiety-like NVP-AUY922 behavior

after SE. This result provides a strong rationale for developing selective inhibitors of TrkB kinase for clinical use. That commencing TrkB kinase inhibition after SE was effective together with the short latency of access to emergency medical care of many patients with SE (Alldredge et al., 2001) enhances the feasibility of this approach to preventive therapy. The fact that just 2 weeks of treatment was sufficient to prevent TLE could minimize potential unwanted effects inherent in long-term exposure to preventive therapy. In sum, TrkB signaling provides an appealing target for developing drugs aimed at prevention of TLE. TrkBF616A and WT mice in a C57BL/6 background (Charles River) were housed under a 12 hr light/dark cycle with food and water provided ad libitum. Animals were handled according to the National Institutes of Health Guide for the Care and Use of the 17-DMAG (Alvespimycin) HCl Laboratory Animals and the experiments were conducted under an approved protocol

by the Duke University Animal Care and Use Committee. Adult mice were anesthetized and a guide cannula was inserted above the right amygdala and a bipolar electrode was inserted into the left hippocampus under stereotaxic guidance (Figure S1A). After a 7-day postoperative recovery, either kainic acid (KA) (0.3 μg in 0.5 μl PBS) or vehicle (0.5 μl of PBS) was infused into the right basolateral amygdala in an awake, gently restrained animal. Hippocampal EEG telemetry (Grass Instrument) and time-locked video monitoring were performed using Harmonie software (Stellate Systems). Monitoring started at least 5 min before amygdala KA infusion for recording baseline EEG and behavioral activity. SE was typically evident electrographically and behaviorally (Mouri et al., 2008) 8–12 min after KA infusion (Figures S3A and S4A). Forty minutes after onset of KA-induced SE, diazepam (10 mg/kg, intraperitoneally [i.p.