RESUMEN
Anxiety disorders are associated with abnormalities in the neural processing of threat-related stimuli. However, the neurobiological mechanisms underlying threat bias in anxiety are not well understood. We recently reported that a Prkar1a heterozygote (Prkar1a(+/-)) mouse with haploinsufficiency for the main regulatory subunit (R1α) of protein kinase A (PKA) exhibits an anxiety-like phenotype associated with increased cAMP signaling in the amygdala. Prkar1a(+/-) mice provide a novel model to test the direct effect of altered PKA expression and subsequent anxiety-like behavioral phenotype on the response to threat. We hypothesized that Prkar1a(+/-)mice would exhibit a bias in threat detection since increased amygdala activity during emotional stimuli is associated with a maladaptive response. We measured behavior and PKA activity in brain areas after exposure to predator or control odor exposure in male Prkar1a(+/-) and wild-type (WT) littermates. Indeed, there were significant differences in the behavioral response to threat detection; WT mice showed the expected response of decrease in exploratory behavior during predator vs. control odor exposure, while Prkar1a(+/-) mice did not alter their behavior between conditions. Basal and total PKA activity was independently associated with genotype, with an interaction between genotype and threat condition. Prkar1a(+/-) mice had higher PKA activity in amygdala and ventromedial hypothalamus in response to predator odor. In contrast, WT mice had higher PKA activity in amygdala and orbitofrontal cortex after exposure to control odor. Dysregulated PKA activity in the amygdala-prefrontal cortex circuitry in Prkar1a(+/-) mice is associated with behavioral phenotype of anxiety and a bias for threat. This is likely related to a failure to inhibit the amydgala response, which is an effect of the genotype. These results suggest that the alteration in PKA signaling in Prkar1a(+/-) mice is not ubiquitous in the brain; tissue-specific effects of the cAMP/PKA pathway are related to threat detection and fear sensitization.
Asunto(s)
Ansiedad/genética , Conducta Animal/fisiología , Encéfalo/enzimología , Subunidad RIalfa de la Proteína Quinasa Dependiente de AMP Cíclico/genética , Mutación , Animales , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones TransgénicosRESUMEN
The present paper deals with the determination of the self-diffusion coefficients of 134 Cs(+) ions in CsI, CsBr and CsCl over the concentration range of 5 x 10(-6)-0.01 M and of electrolyte diffusion coefficients of CsI, CsBr and CsCl (5 x 10(-5)-0.1M) labelled with 134 Cs(+) in 1% agar gel at 25 degrees C. These diffusion coefficients are compared with those expected from the Onsager-Fouss and Onsager's theory for electrolyte and self-diffusion, respectively. The disparity between the theoretical and experimental diffusion coefficients over the wide range of concentrations is accounted on the basis of various types of interactions occurring in the ion-gel-water system.