Second, we demonstrate target-specific modulation of perisomatic CB1R. Last and most important, our study reveals that behavior can trigger target-specific changes in perisomatic synapses. Behavior-induced target-specific plasticity of perisomatic synapses may be a central feature of neural circuits across the brain. In summary, we discovered that contextual fear extinction causes the remodeling of perisomatic inhibitory

synapses located directly selleck chemicals llc around fear neurons in the basal amygdala. This discovery provides an anatomical and functional connection between the extinction circuit and the fear circuit. Since perisomatic synapses directly impinge on the fear circuit, they provide an attractive target for modulating maladaptive fear. In addition, our study reveals a mechanism by which behavior can use inhibitory synapse plasticity to alter the flow of information through the neural circuits. An important goal for future studies will be to determine the extent to which silencing of BA fear neurons is achieved by changes in perisomatic inhibitory synapses versus changes in other inhibitory and excitatory synapses and changes in neuronal excitability. All animal procedures were performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Tufts

University XAV-939 cell line Institutional Animal Care and Use Committee. The TetTag mouse line used in this study was heterozygous for two transgenes: c-fos promoter-driven tetracycline transactivator (cfosP-tTA; Jackson Laboratory stock number 008344) and a tet operator-driven fusion of histone2B and GFP (tetO-His2BGFP; Jackson Laboratory stock number 005104). TetTag mice were backcrossed to a C57Bl6/J background. Thy1-YFP mice were obtained from Jackson Laboratory (line H; stock number 003782). Mice had food and water ad libitum and were socially housed (three to five animals per cage) until the start of the experiment, which was at an age of at least 12 weeks. Mice were kept on a regular light-dark cycle, and all

experimental manipulations were done during the light phase. Mice were raised CYTH4 on food with doxycycline (40 mg doxycycline/kg chow). One week before fear conditioning, all mice were individually housed, and 4 days before fear conditioning, doxycycline was removed from the food. After the last fear conditioning trial on day 1, mice were put on food with a high dose of doxycycline (1 g/kg) to rapidly block the tagging of neurons activated after fear conditioning. On day 2 mice were put back on the regular dose of doxycycline (40 mg/kg). A total of 48 TetTag mice were used for the study. Experiment 1 consisted of a fear conditioning group (FC, n = 15) and a fear conditioning followed by extinction group (FC+EXT, n = 17). Experiment 2 consisted of a home cage group (HC, n = 8) and a fear conditioning group (FC, n = 8). The design of experiment 1 is summarized in Figure 1C.