[PMC free article] [PubMed] [Google Scholar]Warren MS, Bradley WD, Gourley SL, Lin YC, Simpson MA, Reichardt LF, Greer CA, Taylor JR, Koleske AJ

[PMC free article] [PubMed] [Google Scholar]Warren MS, Bradley WD, Gourley SL, Lin YC, Simpson MA, Reichardt LF, Greer CA, Taylor JR, Koleske AJ. of age. These results suggest that ErbB4 signaling in excitatory pyramidal cells is critical for the proper formation and maintenance of dendritic spines in excitatory pyramidal cells. allele were obtained from the Mutant Mouse Regional Resource Center (MMRRC) at UC Davis (Golub et al., 2004). These embryos were implanted in pseudopregnant foster mothers by the Yale Animal Genomics Services and the resulting pups were genotyped with the following primers as per the MMRRC instructions: Primer 1 C 5′ CAAATGCTCTCTCTGTTCTTTGTGTCTG, Primer 2 C 5′ TTTTGCCAAGTT CTAATTCCATCAGAAGC, Primer 3 C 5′ TATTGTGTTCATCTATCATTGCAACCCAG. Mice expressing two copies of the floxed allele were then crossed with the allele and Nestin-Cre (Nestin-Cre), will be referred to as brain specific (allele and Nex-Cre (Nex-Cre) will be referred to as Nestin-Cre, see Materials and Methods) mice were also crossed into a transgenic (M1) mouse line (Feng et al., 2000) to visualize dendritic spines on cortical layer V pyramidal neurons (Fig. 1B). We imaged and analyzed dendritic spines on proximal, middle, and distal segments DUBs-IN-1 of secondary or tertiary apical dendrites of layer V dorsomedial prefrontal cortical neurons. This brain region Rabbit polyclonal to PNPLA2 is believed to correspond to the dorsolateral prefrontal cortex in humans, known to control working memory, perception, emotion, and executive functions (Moghaddam and Homayoun, 2008). At postnatal day 16 (P16), spine density was comparable in WT and reduces total ErbB4 in brain ErbB4 is expressed ubiquitously in the brain and there are clear consequences of loss of ErbB4 from GABAergic interneurons (Chen et al., 2010; Fazzari et al., 2010; Okada and Corfas, 2004; Ting et al., 2011). However, our localization data strongly suggest that in addition to its important functions in interneurons, ErbB4 may act in DUBs-IN-1 excitatory neurons to influence dendritic spine development and stability. To test this, we used a transgene to selectively inactivate in excitatory neurons of the cerebral cortex and hippocampus (mutant animals through P16, spine density is reduced by approximately 20% in mutant mice after P21. Interestingly, the extent of dendritic spine loss in both whole brain and excitatory neuronspecific mutant mice is usually of comparable magnitude to that observed in schizophrenic patients in the prefrontal cortex (Black et al., 2004; Glantz and Lewis, 2000). In addition, the spine loss in em bs-ErbB4 /em ?/? mice was observed in apical dendrite segments in layer II/III (middle segments) where the majority of spines are lost in post-mortem schizophrenic brains. This comparative reduction in spine density in em bs-ErbB4 /em ?/? animals is maintained into adulthood, indicating that this initial impairment does not recover. ErbB4 protein levels persist in adult mice, albeit at lower levels than during the peak of spine maturation and pruning around 3 weeks of age. However, in em Nex-ErbB4 /em ?/? mice the early deficits in spine density in the middle segments DUBs-IN-1 recover by P63. By contrast, the changes in proximal dendrite branches, of em Nex-ErbB4 /em ?/? mice at P21, persist at P63. This difference in the persistence of spine loss may reflect a greater dependence of more proximal spines within deep layer dendrite segments on ErbB4 function for their formation or stability. We observed slight differences in the baseline density of spines in wild type littermate control mice from the distinct em bs-ErbB4 /em ?/? and em Nex-ErbB4 /em ?/? breeding populations, which are likely due to differences in strain background. Importantly, the reduced spine density in both em bs-ErbB4 /em ?/? and em Nex-ErbB4 /em ?/? DUBs-IN-1 mice is mainly due to the.