The subgranular zone of the adult hippocampal dentate gyrus (DG) contains a pool of neural stem cells that continuously divide and differentiate into functional granule cells. The survival of newly born hippocampal neurons is decreased by chronic psychosocial stress and increased by antidepressants or from exposure to enriched environments. These observations suggest a role for adult hippocampal neurogenesis in the regulation of stress-related affective disorders. According to a transgenic mouse model with conditionally suppressed neurogenesis the efficacy of environmental enrichment in reversing the submissive and depressive-like behaviors acquired from chronic exposure to social defeat stress is dependent on adult neurogenesis. Valganciclovir administered to mice expressing herpes-simplex virus thymidine kinase (HSV-tk) under the control of the human GFAP promoter will ablate GFAP-positive cells. Representative images of a mouse on a running wheel, the presence of immature neurons via doublecortin (aqua) and activated microglia via iba1 (pink) in the DG of control mice, and the expression of HSV-tk (green) and GFAP positive cells (red) in the DG of transgenic mice. For more info on this topic, please refer to the article by Schloesser et al. on pages 1152–1163.

Cross section through the hippocampus of a transgenic mouse expressing the GAD67 miRNA under a control of NPY BAC. Note that the NPY+, eGFP-expressing cells (green) cells do not express GAD67 (red), suggesting that we achieved silencing of GAD67 in NPY+ interneurons. For more info on this topic, please refer to the article by Garbett et al on pages 987–995.

Mice housed in environmental enrichment (EE) conditions (left panel) showed an anxiolyticlike phenotype, which was associated with a significant reduction in CRF receptor type 1 (CRFR1) expression in the basolateral amygdala (BLA). A lentiviral-based system of RNA interference was used to genetically mimic the environmental enrichment anxiolytic-like effect in mice housed under standard conditions. In vivo knockdown of CRFR1 mRNA expression in the BLA induced a significant decrease in anxiety-like behavior, similar to the effect achieved by EE nurture. Site of injection was confirmed by an enhanced green fluorescence protein (eGFP) reporter (right panel), co-expressed with the CRFR1 RNA interference sequence. For further information on this topic, please refer to the article by Sztainberg et al. on pages 905–917.

Failure of activation and failure of de-activation during cognitive task performance in schizophrenia. Thirty-two patients with schizophrenia and 32 healthy control subjects were imaged using fMRI while they performed the n-back working memory task. Compared to the controls the patients showed reduced activation in a network of brain regions including the dorsolateral prefrontal cortex (shown in blue).There was also a large area in the medial frontal cortex where they showed failure of de-activation (shown in orange). The right side of the image represents the left side of the brain. For more information on this topic, please refer to the article by Pomarol-Clotet et al. on pages 823–830.

Functional enrichment analysis of ADHD structural variants. Genes disrupted by inherited structural variants identified in ADHD individuals were classified by associated gene ontology terms. The figure depicts a subset of the Gene Ontology graph, with spheres indicating functional nodes and lines indicating relationships between terms. Functional terms that were significantly enriched in genes found to be disrupted in ADHD relative to healthy controls are shaded green, representing (clockwise from left) functional terms learning, hindbrain development, central nervous system development, and cell adhesion. For further information on this topic, see the article by Elia et al on pages 637–646.

Modulation of neutrophil granulocyte adherence to brain ICAM immunoreactivity by leptin. Double immunohistochemistry for intracellular adhesion molecule (ICAM-1, green) and neutrophil granulocytes (7/4 antigen, red) is shown in the brain of lipopolysaccharide (LPS)-treated mice. The majority of 7/4-IR cells (neutrophils) were found adhering to ICAM-1-IR cells, on both the luminal and abluminal (brain) sides of vasculature-like structures suggesting an integrin-mediated neutrophil arrest to the endothelium, the essential step for eventual neutrophil infiltration into the parenchyma. For further information on this topic, including the role of leptin in modulating this process see the article by Rummel et al. on pages 523–534.

Circulating immune cells help the mind under stress conditions: the beneficial feedback loop between the immune system and the brain. For further information on this topic see the articles by M Schwartz on pages 337–338 and M Schwartz and R Shechter on pages 342–354.

Sub-fornical organ (SFO) demonstrates GLUT3 protein in neuronal processes (red), GLUT1 protein in microvessels (green) and DAPI nuclear staining (blue) in the wild type adult mouse brain sections. The glut3+/− mice (not shown) demonstrated a decrease in GLUT3 protein in neuronal processes with no change in microvascular GLUT1. For more information on this topic, please refer to the article by Zhao et al. on pages 286–299.

Many complex diseases, including depression and anxiety disorders, can be initiated by inadequate adaptation to stress. Specifically, prolonged central secretion of corticotropin-releasing hormone (CRH) is believed to account for a number of signs and symptoms characterizing these disorders. Among the symptoms are manifold sleep disturbances, and electroencephalogram (EEG) recordings characterize them by disinhibited raid eye movement (REM) sleep and a decrease of slew-wave sleep. According to a transgenic mouse model with conditional CRH overexpression, CRH accounts for these changes in sleep architecture. Both homozygous CRH-COE-Nes (CNS-specific) and -Cam (forebrain-specific) mice exhibited constantly elevated REM sleep. Representative images of a sleeping CRH-COE-Nes mouse and its EEG patterns. For more information on this topic, please refer to the article by Kimura et al. on pages 154–165.

Cells located within the dorsal dentate gyrus (dDG) of rats injected with lentiviral vectors (LV) expressing green fluorescent protein (GFP). The micrograph in the left is taken from a slice of dDG injected with LV expressing scrambled short hairpin RNA (LV-shSCR; control), while the micrograph in the right is taken from a slice of dDG injected with LV expressing short hairpin RNA complementary to the coding sequence of BDNF (LV-shBDNF; BDNF knockdown). The micrographs present superimposition of cells expressing GFP as an infection marker (green) and BDNF protein (red). Note the significant reduction in BDNF expression induced by the LV-shBDNF microinjection and the absence of BDNF in the infected cells in the right panel. For more information on this topic, please refer to the article by Taliaz et al on pages 80–92.