Glucocorticoids (GCs) secreted after stress reduce adult hippocampal neurogenesis, a process that has been implicated in cognitive aspects of psychopathology, amongst others. Yet, the exact role of... Show moreGlucocorticoids (GCs) secreted after stress reduce adult hippocampal neurogenesis, a process that has been implicated in cognitive aspects of psychopathology, amongst others. Yet, the exact role of the GC receptor (GR), a key mediator of GC action, in regulating adult neurogenesis is largely unknown. Here, we show that GR knockdown, selectively in newborn cells of the hippocampal neurogenic niche, accelerates their neuronal differentiation and migration. Strikingly, GR knockdown induced ectopic positioning of a subset of the new granule cells, altered their dendritic complexity and increased their number of mature dendritic spines and mossy fiber boutons. Consistent with the increase in synaptic contacts, cells with GR knockdown exhibit increased basal excitability parallel to impaired contextual freezing during fear conditioning. Together, our data demonstrate a key role for the GR in newborn hippocampal cells in mediating their synaptic connectivity and structural as well as functional integration into mature hippocampal circuits involved in fear memory consolidation. Show less
Schenk, G.J.; Veldhuisen, B.; Wedemeier, O.; McGown, C.C.; Schouten, T.G.; Oitzl, M.; ... ; Vreugdenhil, E. 2010
Products of the Doublecortin-Like Kinase (DCLK) gene are associated with cortical migration and hippocampal maturation during embryogenesis However the functions of those DCLK gene transcripts that... Show moreProducts of the Doublecortin-Like Kinase (DCLK) gene are associated with cortical migration and hippocampal maturation during embryogenesis However the functions of those DCLK gene transcripts that encode kinases and are expressed during adulthood are Incompletely understood To elucidate potential functions of these DCLK gene splice variants we have generated and analyzed transgenic mice with neuronal over-expression of a truncated constitutively active form of DCLK-short designated delta C-DCLK-short Previously we have performed an extensive molecular characterization of these transgenic delta C-DCLK-short mice and established that a specific subunit of the GABA(A) receptor which is involved in anxiety-related GABAergic neurotransmission is down regulated in the hippocampus Here we show that delta C-DCLK-short mRNA is highly expressed in the hippocampus cortex and amygdala of transgenic mice We provide evidence that the delta C DCLK-short protein is expressed and functional In addition we examined anxiety-related behavior in delta C-DCLK short mice in the elevated plus maze Interestingly delta C-DCLK-short mice spend less time move less in the open arms of the maze and show a reduction in the number of rim dips These behaviors indicate that delta C DCLK-short mice display a more anxious behavioral phenotype (C) 2010 Elsevier Inc All rights reserved Show less
