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Social Stress Engages Neurochemically-Distinct Afferents to the Rat Locus Coeruleus Depending on Coping Strategy.

Reyes BA, Zitnik G, Foster C, Van Bockstaele EJ, Valentino RJ - eNeuro (2015)

Bottom Line: Sections through the nucleus paragigantocellularis (PGi) and central amygdalar nucleus (CNA), major sources of enkephalin (ENK) and CRF LC afferents, respectively, were immunocytochemically processed to detect c-fos, FG, and CRF or ENK.Together, these results indicate that the establishment of different coping strategies to social stress is associated with changes in the circuitry that regulates activity of the brain norepinephrine system.This may underlie differential vulnerability to the consequences of social stress that characterize these different coping strategies.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology and Physiology, College of Medicine, Drexel University , Philadelphia, Pennsylvania 19102.

ABSTRACT
Stress increases vulnerability to psychiatric disorders, partly by affecting brain monoamine systems, such as the locus coeruleus (LC)-norepinephrine system. During stress, LC activity is coregulated by corticotropin-releasing factor (CRF) and endogenous opioids. This study identified neural circuitry that regulates LC activity of intruder rats during the resident-intruder model of social stress. LC afferents were retrogradely labeled with Fluorogold (FG) and rats were subjected to one or five daily exposures to an aggressive resident. Sections through the nucleus paragigantocellularis (PGi) and central amygdalar nucleus (CNA), major sources of enkephalin (ENK) and CRF LC afferents, respectively, were immunocytochemically processed to detect c-fos, FG, and CRF or ENK. In response to a single exposure, intruder rats assumed defeat with a relatively short latency (SL). LC neurons, PGI-ENK LC afferents, and CNA-CRF LC afferents were activated in these rats as indicated by increased c-fos expression. With repeated stress, rats exhibited either a SL or long latency (LL) to defeat and these strategies were associated with distinct patterns of neuronal activation. In SL rats, LC neurons were activated, as were CNA-CRF LC afferents but not PGI-ENK LC afferents. LL rats had an opposite pattern, maintaining activation of PGi-ENK LC afferents but not CNA-CRF LC afferents or LC neurons. Together, these results indicate that the establishment of different coping strategies to social stress is associated with changes in the circuitry that regulates activity of the brain norepinephrine system. This may underlie differential vulnerability to the consequences of social stress that characterize these different coping strategies.

No MeSH data available.


Related in: MedlinePlus

Activation of LC-projecting corticotropin-releasing factor neurons in the CNA. A, Scatterplot showing the percentage of FG-c-fos-labeled neurons that were also immunolabeled for CRF for individual control, SL, and LL rats. Lines through the points indicate the group mean. B, Representative immunofluorescence photomicrograph from a SL rat showing c-fos profiles (blue), FG labeling (green), CRF-immunoreactivity (red), and triple-labeled neurons (yellow). Arrows point to single-labeled neurons and arrowheads point to triple-labeled neurons. Scale bar, 10 μm. C, High-magnification photomicrographs illustrating activated LC-projecting CRF neurons in the CNA of a SL rat. FG, c-fos, and CRF panels show single labeling for the retrograde tracer, FG (green), c-fos immunoreactivity (blue), and CRF immunoreactivity (red), respectively. The merged image shows all labels. Thin arrows point to the same triple-labeled neuron in all images. Scale bar, 10 μm.
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Figure 3: Activation of LC-projecting corticotropin-releasing factor neurons in the CNA. A, Scatterplot showing the percentage of FG-c-fos-labeled neurons that were also immunolabeled for CRF for individual control, SL, and LL rats. Lines through the points indicate the group mean. B, Representative immunofluorescence photomicrograph from a SL rat showing c-fos profiles (blue), FG labeling (green), CRF-immunoreactivity (red), and triple-labeled neurons (yellow). Arrows point to single-labeled neurons and arrowheads point to triple-labeled neurons. Scale bar, 10 μm. C, High-magnification photomicrographs illustrating activated LC-projecting CRF neurons in the CNA of a SL rat. FG, c-fos, and CRF panels show single labeling for the retrograde tracer, FG (green), c-fos immunoreactivity (blue), and CRF immunoreactivity (red), respectively. The merged image shows all labels. Thin arrows point to the same triple-labeled neuron in all images. Scale bar, 10 μm.

Mentions: Figure 3 shows examples of FG, c-fos, and CRF immunolabeling in the CNA. In direct contrast to the patterns of activation within the PGi, more CNA neurons overall were activated in SL rats compared with LL or control rats based on the number of c-fos profiles (F(2,8) = 33, p = 0.0001; Table 2) and more CNA LC-afferents were activated in SL rats compared with other groups (FG+c-fos; F(2,8) = 40, p < 0.0001; Table 2). Notably, CRF-immunolabeled neurons were more numerous in the CNA of SL rats compared with all other groups (F(2,8) = 20, p = 0.0007; Table 2). Moreover, SL rats showed greater activation of CRF-LC-projecting neurons as indicated by the percentage of CRF-immunolabeled LC-projecting neurons exhibiting c-fos immunolabeling compared with both controls and LL rats (F(2,8) = 43, p < 0.0001; Table 2). There was a tendency for more triple-labeled neurons in LL rats compared with controls (p = 0.052, Tukey's HSD).


Social Stress Engages Neurochemically-Distinct Afferents to the Rat Locus Coeruleus Depending on Coping Strategy.

Reyes BA, Zitnik G, Foster C, Van Bockstaele EJ, Valentino RJ - eNeuro (2015)

Activation of LC-projecting corticotropin-releasing factor neurons in the CNA. A, Scatterplot showing the percentage of FG-c-fos-labeled neurons that were also immunolabeled for CRF for individual control, SL, and LL rats. Lines through the points indicate the group mean. B, Representative immunofluorescence photomicrograph from a SL rat showing c-fos profiles (blue), FG labeling (green), CRF-immunoreactivity (red), and triple-labeled neurons (yellow). Arrows point to single-labeled neurons and arrowheads point to triple-labeled neurons. Scale bar, 10 μm. C, High-magnification photomicrographs illustrating activated LC-projecting CRF neurons in the CNA of a SL rat. FG, c-fos, and CRF panels show single labeling for the retrograde tracer, FG (green), c-fos immunoreactivity (blue), and CRF immunoreactivity (red), respectively. The merged image shows all labels. Thin arrows point to the same triple-labeled neuron in all images. Scale bar, 10 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4660134&req=5

Figure 3: Activation of LC-projecting corticotropin-releasing factor neurons in the CNA. A, Scatterplot showing the percentage of FG-c-fos-labeled neurons that were also immunolabeled for CRF for individual control, SL, and LL rats. Lines through the points indicate the group mean. B, Representative immunofluorescence photomicrograph from a SL rat showing c-fos profiles (blue), FG labeling (green), CRF-immunoreactivity (red), and triple-labeled neurons (yellow). Arrows point to single-labeled neurons and arrowheads point to triple-labeled neurons. Scale bar, 10 μm. C, High-magnification photomicrographs illustrating activated LC-projecting CRF neurons in the CNA of a SL rat. FG, c-fos, and CRF panels show single labeling for the retrograde tracer, FG (green), c-fos immunoreactivity (blue), and CRF immunoreactivity (red), respectively. The merged image shows all labels. Thin arrows point to the same triple-labeled neuron in all images. Scale bar, 10 μm.
Mentions: Figure 3 shows examples of FG, c-fos, and CRF immunolabeling in the CNA. In direct contrast to the patterns of activation within the PGi, more CNA neurons overall were activated in SL rats compared with LL or control rats based on the number of c-fos profiles (F(2,8) = 33, p = 0.0001; Table 2) and more CNA LC-afferents were activated in SL rats compared with other groups (FG+c-fos; F(2,8) = 40, p < 0.0001; Table 2). Notably, CRF-immunolabeled neurons were more numerous in the CNA of SL rats compared with all other groups (F(2,8) = 20, p = 0.0007; Table 2). Moreover, SL rats showed greater activation of CRF-LC-projecting neurons as indicated by the percentage of CRF-immunolabeled LC-projecting neurons exhibiting c-fos immunolabeling compared with both controls and LL rats (F(2,8) = 43, p < 0.0001; Table 2). There was a tendency for more triple-labeled neurons in LL rats compared with controls (p = 0.052, Tukey's HSD).

Bottom Line: Sections through the nucleus paragigantocellularis (PGi) and central amygdalar nucleus (CNA), major sources of enkephalin (ENK) and CRF LC afferents, respectively, were immunocytochemically processed to detect c-fos, FG, and CRF or ENK.Together, these results indicate that the establishment of different coping strategies to social stress is associated with changes in the circuitry that regulates activity of the brain norepinephrine system.This may underlie differential vulnerability to the consequences of social stress that characterize these different coping strategies.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology and Physiology, College of Medicine, Drexel University , Philadelphia, Pennsylvania 19102.

ABSTRACT
Stress increases vulnerability to psychiatric disorders, partly by affecting brain monoamine systems, such as the locus coeruleus (LC)-norepinephrine system. During stress, LC activity is coregulated by corticotropin-releasing factor (CRF) and endogenous opioids. This study identified neural circuitry that regulates LC activity of intruder rats during the resident-intruder model of social stress. LC afferents were retrogradely labeled with Fluorogold (FG) and rats were subjected to one or five daily exposures to an aggressive resident. Sections through the nucleus paragigantocellularis (PGi) and central amygdalar nucleus (CNA), major sources of enkephalin (ENK) and CRF LC afferents, respectively, were immunocytochemically processed to detect c-fos, FG, and CRF or ENK. In response to a single exposure, intruder rats assumed defeat with a relatively short latency (SL). LC neurons, PGI-ENK LC afferents, and CNA-CRF LC afferents were activated in these rats as indicated by increased c-fos expression. With repeated stress, rats exhibited either a SL or long latency (LL) to defeat and these strategies were associated with distinct patterns of neuronal activation. In SL rats, LC neurons were activated, as were CNA-CRF LC afferents but not PGI-ENK LC afferents. LL rats had an opposite pattern, maintaining activation of PGi-ENK LC afferents but not CNA-CRF LC afferents or LC neurons. Together, these results indicate that the establishment of different coping strategies to social stress is associated with changes in the circuitry that regulates activity of the brain norepinephrine system. This may underlie differential vulnerability to the consequences of social stress that characterize these different coping strategies.

No MeSH data available.


Related in: MedlinePlus