Fox urine exposure induces avoidance behavior in rats and activates the amygdalar olfactory cortex.

Predator odors represent a group of biologically-relevant chemosignals called kairomones. Kairomones enable prey animals to recognize potential predatory threats in their environment and to initiate appropriate defensive responses. Although the behavioral repertoire of anti-predatory responses (e.g. avoidance, freezing, risk assessment) has been investigated extensively, our knowledge about the neural network mediating these innate fear responses is rather limited. In the present study, the GABAA agonist muscimol was bilaterally injected (2.6 nmol/0.3 µl) into the amygdalar olfactory cortex (AOC), a brain area that receives massive olfactory input from both olfactory systems and is strongly interconnected with the medial hypothalamic defense circuit. Temporary inactivation of the AOC substantially disrupted avoidance behavior of rats to fox urine that is strongly avoided under control conditions (saline injections). Taken together, these results demonstrate that the AOC is critically involved in fox urine-induced fear behavior. This suggests that the AOC is part of a brain fear circuit that mediates innate fear responses toward predatory odors.

TMT predator odor activated neural circuit in C57BL/6J mice indicates TMT-stress as a suitable model for uncontrollable intense stress.

Intense stressful events can result in chronic disorders such as posttraumatic stress disorder (PTSD). In vulnerable individuals, a single aversive experience can be sufficient to cause long-lasting behavioral changes. Candidate brain regions implicated in stress-related psychopathology are the amygdala, the bed nucleus of the stria terminalis (BNST), and the hypothalamic pituitary adrenal (HPA) axis. In rodents exposure to 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), an ethologically relevant stressor, has been shown to induce intense stress and innate anxiety responses. To study dispositions for the development of maladaptive stress responses, mice models are required. Therefore C57BL/6J mice were exposed to TMT and Fos expression was studied in key brain regions implicated in stress responses and anxiety-like behavior. Our results show TMT-induced activation of a distinct neural circuit involving the BNST, the lateral septum (LS), the paraventricular nucleus of the hypothalamus (PVN), the periaqueductal gray (PAG) and the locus coeruleus (LC). Anatomical interconnection of the BNST with all these regions could point to an important modulatory role of this nucleus. Since, the BNST gets direct input from the olfactory bulbs and projects to the PVN and PAG and is therefore well positioned to modulate behavioral and endocrine stress responses to TMT. Hence, we suggest that TMT exposure is suitable to investigate uncontrollable stress responses in mice which exhibit similarities to maladaptive stress responses underlying PTSD in humans.

Impaired Pavlovian fear extinction is a common phenotype across genetic lineages of the 129 inbred mouse strain.

Fear extinction is impaired in psychiatric disorders such as post-traumatic stress disorder and schizophrenia, which have a major genetic component. However, the genetic factors underlying individual variability in fear extinction remain to be determined. By comparing a panel of inbred mouse strains, we recently identified a strain, 129S1/SvImJ (129S1), that exhibits a profound and selective deficit in Pavlovian fear extinction, and associated abnormalities in functional activation of a key prefrontal-amygdala circuit, as compared with C57BL/6J. The first aim of the present study was to assess fear extinction across multiple 129 substrains representing the strain's four different genetic lineages (parental, steel, teratoma and contaminated). Results showed that 129P1/ReJ, 129P3/J, 129T2/SvEmsJ and 129X1/SvJ exhibited poor fear extinction, relative to C57BL/6J, while 129S1 showed evidence of fear incubation. On the basis of these results, the second aim was to further characterize the nature and specificity of the extinction phenotype in 129S1, as an exemplar of the 129 substrains. Results showed that the extinction deficit in 129S1 was neither the result of a failure to habituate to a sensitized fear response nor an artifact of a fear response to (unconditioned) tone per se. A stronger conditioning protocol (i.e. five x higher intensity shocks) produced an increase in fear expression in 129S1, relative to C57BL/6J, due to rapid rise in freezing during tone presentation. Taken together, these data show that impaired fear extinction is a phenotypic feature common across 129 substrains, and provide preliminary evidence that impaired fear extinction in 129S1 may reflect a pro-fear incubation-like process.

Topography of thalamic and parabrachial calcitonin gene-related peptide (CGRP) immunoreactive neurons projecting to subnuclei of the amygdala and extended amygdala.

Injections of calcitonin gene-related peptide (CGRP) into the amygdala evoke fear-related behaviors and antinociceptive effects. In the present study we therefore characterized CGRP-containing amygdaloid afferents by injecting the retrograde tracer FluoroGold (FG) into subnuclei of the amygdala and adjacent divisions of the extended amygdala, namely, the lateral (LA) and central (CE) amygdaloid nuclei, interstitial nucleus of the posterior limb of the anterior commissure (IPAC), and the amygdalostriatal area (AStr). The distribution of retrogradely FG-labeled neurons and colocalization of CGRP-immunoreactivity with FG-labeling were mapped in the posterior paralaminar thalamic complex and parabrachial nuclei. The analysis of the posterior thalamus revealed that about 50% of CGRP-containing neurons projected to the AStr, the projections originating in the medial part of the medial geniculate body, posterior intralaminar nucleus, parvicellular subparafascicular nucleus, and peripeduncular nucleus. However, the percentage of CGRP-containing thalamic neurons projecting to the adjacent LA, medial part of the CE, and ventrocaudal part of the caudatoputamen rapidly dropped to 3-9%. There were no double-labeled cells after injections into the lateral and capsular parts of the CE and the IPAC. Thus, the AStr received the heaviest CGRP-containing projection from the posterior thalamus. CGRP-containing parabrachial neurons projected to the AStr and lateral, capsular, and medial parts of the CE, the projections originating in the external, crescent, and central parts of the lateral parabrachial nucleus and external part of the medial parabrachial nucleus. The results demonstrate a distinct projection pattern of CGRP-containing thalamic and parabrachial neurons to subnuclei of the amygdala and extended amygdala.