Anxiety disorders, such as post-traumatic stress, are more prevalent in women and are characterized by impaired inhibition of learned fear and medial prefrontal cortex (mPFC) dysfunction. Here we examined sex differences in fear extinction and mPFC activity in rats. Females showed more learned fear expression during extinction and its recall, but not fear conditioning. They also showed more spontaneous fear recovery and more contextual fear before extinction and its recall. Moreover, enhanced learned fear expression in females was associated with sustained prelimbic (PL) cortex activity. These results suggest that sex differences in learned fear expression may involve persistent PL activation.Women are at increased risk of developing fear-related anxiety disorders compared to men. For example, the prevalence of posttraumatic stress disorder (PTSD) is twice as high in women as in men (Lebron-Milad and Milad 2012). These disorders are characterized by impaired inhibition of learned fear (Milad et al. 2009a;Jovanovic et al. 2010) and a growing number of studies in humans and animals have shown sex differences in fear extinction (Milad et al. 2006;Baran et al. 2009Baran et al. , 2010Glover et al. 2012;ter Horst et al. 2012;Baker-Andresen et al. 2013), the reduction in learned fear that occurs with repeated nonreinforced presentations of the conditioned stimulus (CS).The neural circuitry mediating fear extinction is dysfunctional in PTSD. The medial prefrontal cortex (mPFC) is a heterogeneous area that plays a crucial role in this circuit through its involvement in learned fear and extinction processing. The dorsal anterior cingulate cortex (dACC) in humans and its rodent homolog, the prelimbic cortex (PL), are important for conditioned fear expression. In contrast, the human ventromedial prefrontal cortex (vmPFC) and the homologous infralimbic cortex (IL) in rodents are involved in fear suppression and extinction (Vidal-Gonzalez et al. 2006;Sierra-Mercado et al. 2011;Linnman et al. 2012). Importantly, PTSD is associated with dACC and vmPFC dysfunction (Milad et al. 2009a;Shin et al. 2009). Although a role for mPFC in mediating sex differences in fear extinction is emerging (Baran et al. 2010;Zeidan et al. 2011;Merz et al. 2012), the potential contribution of individual mPFC subregions remains unknown.We examined sex differences in local field potential (LFP) activity in PL and IL during fear extinction in male and naturally cycling female Lister hooded rats (Harlan, UK). All experimental procedures were conducted with internal ethical approval and in accordance with the Animals (Scientific Procedures) Act 1986, UK. Electrodes (Teflon-coated stainless-steel wires, 50 mm diameter) were implanted into PL and IL (2.7 mm anterior and 0.5 mm lateral to bregma, 3.3 mm (PL) and 4.3 mm (IL) ventral to the brain surface) under isoflurane anesthesia. Rats received peri-and post-operative analgesia (buprenorphine and meloxicam) and were singly housed during recovery and behavioral testing, which started 10 -14 d after surgery. ...

Muscle strength is a key clinical parameter used to monitor the progression of human muscular dystrophies, including Duchenne and Becker muscular dystrophies. Although Caenorhabditis elegans is an established genetic model for studying the mechanisms and treatments of muscular dystrophies, analogous strength-based measurements in this disease model are lacking. Here, we describe the first demonstration of the direct measurement of muscular strength in dystrophin-deficient C. elegans mutants using a micropillar-based force measurement system called NemaFlex. We show that dys-1(eg33) mutants, but not dys-1(cx18) mutants, are significantly weaker than their wild-type counterparts in early adulthood, cannot thrash in liquid at wild-type rates, display mitochondrial network fragmentation in the body wall muscles, and have an abnormally high baseline mitochondrial respiration. Furthermore, treatment with prednisone, the standard treatment for muscular dystrophy in humans, and melatonin both improve muscular strength, thrashing rate and mitochondrial network integrity in dys-1(eg33), and prednisone treatment also returns baseline respiration to normal levels. Thus, our results demonstrate that the dys-1(eg33) strain is more clinically relevant than dys-1(cx18) for muscular dystrophy studies in C. elegans. This finding, in combination with the novel NemaFlex platform, can be used as an efficient workflow for identifying candidate compounds that can improve strength in the C. elegans muscular dystrophy model. Our study also lays the foundation for further probing of the mechanism of muscle function loss in dystrophin-deficient C. elegans, leading to knowledge translatable to human muscular dystrophy.