T 2 weeks of CUS had better long-term memory for platform location. Although stressors increase corticosterone, which has damaging effects on the brain (see [6] for review), a large literature attests to the idea that stress does not necessarily detract from learning, and may even enhance it. Indeed, a great many variables influence thisA Stressful Learning Experience Altered Expression of Plasticity-associated Proteins in a Region-specific MannerIn order to determine whether an experience that was both stressful and involved spatial navigation would differentially affect protein expression in the dorsal and ventral DG subregions, Western blotting was used to quantify expression of mature BDNF, its precursor proBDNF and the synaptic scaffolding protein, PSD-95. Rats were sacrificed after completion of the long-term memory trial in the RAWM. One dorsal sample from a control animal was omitted because there was too little protein to be detected. For BDNF, there were no significant differences between groups in either the dorsal or ventral subregions (see Figure 4A). However, RAWM experience significantly increased proBDNF in the dorsal sub-region, and significantly KDM5A-IN-1 biological activity decreased it in the ventral (see Figure 4B). RAWM experience did not change 76932-56-4 site PSD-95 expression in the dorsal DG, but significantly elevated it in the ventral (see Figure 4C).Hippocampal Subregions, Stress and LearningFigure 3. Stress most severely affected neurogenesis in the ventral dentate gyrus. Compared with controls, rats in the CUS group showed decreased proliferation (A), survival (B) and neuronal differentiation (C) in the dentate gyrus. This effect was most pronounced in the ventral, compared to the dorsal, sub-region ({ indicates significant difference between subregions). * significantly different from control. doi:10.1371/journal.pone.0053126.grelationship, such as the type of stress and the type and difficulty of the learning task (see [31] for review). In the case of spatial learning, adaptive stress-induced plasticity in the dorsal hippocampus may preserve or enhance learning and other adaptive responses. The results of the present study, including enhanced long-term spatial memory, and the lack of any stress-induced decrement in performance during acquisition trials, suggests that the dorsal hippocampus may be stress-resilient, resulting in preserved, or even enhanced capacity to make adaptive responses.Figure 4. A stressful spatial navigation task differentially affected protein expression in the dorsal and ventral subregions. Expression of mature BDNF was not significantly changed by RAWM exposure in either the dorsal or ventral dentate gyrus (A). In contrast, proBDNF was significantly increased in the dorsal dentate, and significantly decreased in the ventral (C). PSD-95 was unchanged in the dorsal, but significantly increased in the ventral dentate (C). * significantly different from control. doi:10.1371/journal.pone.0053126.gHippocampal Subregions, Stress and LearningChronic Unpredictable Stress most Severely Affected Neurogenesis in the Ventral SubregionWe have previously shown that survival of newborn cells was better preserved in the dorsal dentate (compared to the ventral) following CUS [9]. In the present study, we used stereology to quantify proliferating cells labeled by CldU 2 hours prior to sacrifice, and surviving cells labeled by IdU during the first five days of the CUS paradigm. We found that CUS decreased the number of CldU+ cells in both the d.T 2 weeks of CUS had better long-term memory for platform location. Although stressors increase corticosterone, which has damaging effects on the brain (see [6] for review), a large literature attests to the idea that stress does not necessarily detract from learning, and may even enhance it. Indeed, a great many variables influence thisA Stressful Learning Experience Altered Expression of Plasticity-associated Proteins in a Region-specific MannerIn order to determine whether an experience that was both stressful and involved spatial navigation would differentially affect protein expression in the dorsal and ventral DG subregions, Western blotting was used to quantify expression of mature BDNF, its precursor proBDNF and the synaptic scaffolding protein, PSD-95. Rats were sacrificed after completion of the long-term memory trial in the RAWM. One dorsal sample from a control animal was omitted because there was too little protein to be detected. For BDNF, there were no significant differences between groups in either the dorsal or ventral subregions (see Figure 4A). However, RAWM experience significantly increased proBDNF in the dorsal sub-region, and significantly decreased it in the ventral (see Figure 4B). RAWM experience did not change PSD-95 expression in the dorsal DG, but significantly elevated it in the ventral (see Figure 4C).Hippocampal Subregions, Stress and LearningFigure 3. Stress most severely affected neurogenesis in the ventral dentate gyrus. Compared with controls, rats in the CUS group showed decreased proliferation (A), survival (B) and neuronal differentiation (C) in the dentate gyrus. This effect was most pronounced in the ventral, compared to the dorsal, sub-region ({ indicates significant difference between subregions). * significantly different from control. doi:10.1371/journal.pone.0053126.grelationship, such as the type of stress and the type and difficulty of the learning task (see [31] for review). In the case of spatial learning, adaptive stress-induced plasticity in the dorsal hippocampus may preserve or enhance learning and other adaptive responses. The results of the present study, including enhanced long-term spatial memory, and the lack of any stress-induced decrement in performance during acquisition trials, suggests that the dorsal hippocampus may be stress-resilient, resulting in preserved, or even enhanced capacity to make adaptive responses.Figure 4. A stressful spatial navigation task differentially affected protein expression in the dorsal and ventral subregions. Expression of mature BDNF was not significantly changed by RAWM exposure in either the dorsal or ventral dentate gyrus (A). In contrast, proBDNF was significantly increased in the dorsal dentate, and significantly decreased in the ventral (C). PSD-95 was unchanged in the dorsal, but significantly increased in the ventral dentate (C). * significantly different from control. doi:10.1371/journal.pone.0053126.gHippocampal Subregions, Stress and LearningChronic Unpredictable Stress most Severely Affected Neurogenesis in the Ventral SubregionWe have previously shown that survival of newborn cells was better preserved in the dorsal dentate (compared to the ventral) following CUS [9]. In the present study, we used stereology to quantify proliferating cells labeled by CldU 2 hours prior to sacrifice, and surviving cells labeled by IdU during the first five days of the CUS paradigm. We found that CUS decreased the number of CldU+ cells in both the d.