| First Author | Meins M | Year | 2010 |
| Journal | Eur J Neurosci | Volume | 31 |
| Issue | 11 | Pages | 2033-42 |
| PubMed ID | 20529116 | Mgi Jnum | J:163031 |
| Mgi Id | MGI:4820921 | Doi | 10.1111/j.1460-9568.2010.07221.x |
| Citation | Meins M, et al. (2010) Impaired fear extinction in mice lacking protease nexin-1. Eur J Neurosci 31(11):2033-42 |
| abstractText | The serine protease inhibitor protease-nexin-1 (PN-1) has been shown to modulate N-methyl-d-aspartate receptor (NMDAR)-mediated synaptic currents and NMDAR-dependent long-term potentiation of synaptic transmission. Here, we analysed the role of PN-1 in the acquisition and extinction of classical auditory fear conditioning, two distinct forms of learning that both depend on NMDAR activity in the amygdala. Immunostaining revealed that PN-1 is expressed throughout the amygdala, primarily in gamma-aminobutyric acid containing neurons of the central amygdala and intercalated cell masses (ITCs) and in glia. Fear extinction was severely impaired in mice lacking PN-1 (PN-1 KO). Consistent with a role for the basal nucleus of the amygdala in fear extinction, we found that, compared with wild-type (WT) littermate controls, PN-1 KO mice exhibited decreased numbers of Fos-positive neurons in the basal nucleus after extinction. Moreover, immunoblot analysis of laser-microdissected amygdala sub-nuclei revealed specific extinction-induced increases in the level of phosphorylated alpha-calcium/calmodulin protein kinase II in the medial ITCs and in the lateral subdivision of the central amygdala in WT mice. These responses were altered in PN-1 KO mice. Together, these data indicate that lack of extinction in PN-1 KO mice is associated with distinct changes in neuronal activity across the circuitry of the basal and central nuclei and the ITCs, supporting a differential impact on fear extinction of these amygdala substructures. They also suggest a new role for serine protease inhibitors such as PN-1 in modulating fear conditioning and extinction. |
