Nevertheless, these data are in line with recent studies demonstrating a link between impaired extinction learning and altered immediate-early gene expression patterns in the BA, mITC and CEA in select mouse and rat strains with inborn behavioral deficits (Hefner et al., 2008; Muigg TSA HDAC ic50 et al., 2009) and with

the recovery of conditioned fear responses in extinguished animals after attenuation of glutamatergic input to mITCs or targeted immunotoxic lesions of mITCs (Jüngling et al., 2008; Likhtik et al., 2008). In summary, our results support a growing view that the emotional learning and memory system is not limited to the BLA but is distributed across BLA, ITC and CEA circuitry of the amygdala (Paréet al., 2004; Wilensky et al., 2006). Moreover, our study demonstrates that lack of PN-1 results in area-specific changes in signaling activity markers underlying fear extinction. Serine proteases and their inhibitors may thus represent new targets for intervention in various conditions associated with anxiety and stress. This work was supported by grants from the Swiss National Science Foundation, the Austrian Science Fund, the Volkswagen Stiftung and by the Novartis Research Foundation. We thank Sabrina Djaffer for expert animal breeding and care, Erik Cabuy for advice about laser dissection,

Sandrine Bichet for help with immunohistochemistry, Laurent Gelman for patient help with microscopy, and Cédric Fischer for help at the start of this work. We also thank Andrew Matus and Thomas Oertner for critical reading of the manuscript. Abbreviations BA basal nucleus of the amygdala BLA basolateral amygdaloid ICG-001 manufacturer complex CEA central nucleus of the amygdala CEl latero-capsular subdivision of the central amygdala CEm medial subdivision of the central amygdala CS conditioned

stimulus ext. extinction GABAergic γ-aminobutyric acid containing inhibitory neurons GAD67 glutamic acid dehydrogenase 67-kD isoform GFAP glial fibrillary acidic protein ITCs intercalated new cell masses LA lateral nucleus of the amygdala lITC lateral intercalated cell mass mITC medial intercalated cell mass NMDAR N-methyl-d-aspartate receptor no ext. no extinction PAR-1 protease-activated receptor-1 PN-1 KO mouse line lacking in protease nexin-1 PN-1 protease nexin-1 pαCamKII phosphorylated alpha-calcium/calmodulin protein kinase II US unconditioned stimulus WT wild-type littermates of PN-1 KO mice αCamKII alpha-calcium/calmodulin protein kinase II Fig. S1. Behavioral data for mice used for biochemical experiments. Fig. S2. αCamKII/actin does not show genotype dependence. Fig. S3. pαCamKII levels show no behavior dependence in LA and BA. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer-reviewed and may be re-organized for online delivery, but are not copy-edited or typeset by Wiley-Blackwell.