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Neuroscience and Neurobiology

Neurons

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Wandering Neuronal Migration In The Postnatal Vertebrate Forebrain, Benjamin Scott, Timothy Gardner, Ni Ji, Michale Fee, Carlos Lois May 2013

Wandering Neuronal Migration In The Postnatal Vertebrate Forebrain, Benjamin Scott, Timothy Gardner, Ni Ji, Michale Fee, Carlos Lois

Carlos Lois

Most non-mammalian vertebrate species add new neurons to existing brain circuits throughout life, a process thought to be essential for tissue maintenance, repair, and learning. How these new neurons migrate through the mature brain and which cues trigger their integration within a functioning circuit is not known. To address these questions, we used two-photon microscopy to image the addition of genetically labeled newly generated neurons into the brain of juvenile zebra finches. Time-lapse in vivo imaging revealed that the majority of migratory new neurons exhibited a multipolar morphology and moved in a nonlinear manner for hundreds of micrometers. Young neurons …


Genetic Labeling Of Neuronal Subsets Through Enhancer Trapping In Mice, Wolfgang Kelsch, Alberto Stolfi, Carlos Lois May 2013

Genetic Labeling Of Neuronal Subsets Through Enhancer Trapping In Mice, Wolfgang Kelsch, Alberto Stolfi, Carlos Lois

Carlos Lois

The ability to label, visualize, and manipulate subsets of neurons is critical for elucidating the structure and function of individual cell types in the brain. Enhancer trapping has proved extremely useful for the genetic manipulation of selective cell types in Drosophila. We have developed an enhancer trap strategy in mammals by generating transgenic mice with lentiviral vectors carrying single-copy enhancer-detector probes encoding either the marker gene lacZ or Cre recombinase. This transgenic strategy allowed us to genetically identify a wide variety of neuronal subpopulations in distinct brain regions. Enhancer detection by lentiviral transgenesis could thus provide a complementary method for …


Similarity Of Visual Selectivity Among Clonally Related Neurons In Visual Cortex, Gen Ohtsuki, Megumi Nishiyama, Takashi Yoshida, Tomonari Murakami, Mark Histed, Carlos Lois, Kenichi Ohki May 2013

Similarity Of Visual Selectivity Among Clonally Related Neurons In Visual Cortex, Gen Ohtsuki, Megumi Nishiyama, Takashi Yoshida, Tomonari Murakami, Mark Histed, Carlos Lois, Kenichi Ohki

Carlos Lois

Neurons in rodent visual cortex are organized in a salt-and-pepper fashion for orientation selectivity, but it is still unknown how this functional architecture develops. A recent study reported that the progeny of single cortical progenitor cells are preferentially connected in the postnatal cortex. If these neurons acquire similar selectivity through their connections, a salt-and-pepper organization may be generated, because neurons derived from different progenitors are intermingled in rodents. Here we investigated whether clonally related cells have similar preferred orientation by using a transgenic mouse, which labels all the progeny of single cortical progenitor cells. We found that preferred orientations of …


Increasing Heterogeneity In The Organization Of Synaptic Inputs Of Mature Olfactory Bulb Neurons Generated In Newborn Rats, Wolfgang Kelsch, Shuyin Sim, Carlos Lois May 2013

Increasing Heterogeneity In The Organization Of Synaptic Inputs Of Mature Olfactory Bulb Neurons Generated In Newborn Rats, Wolfgang Kelsch, Shuyin Sim, Carlos Lois

Carlos Lois

New neurons are added into the mammalian olfactory bulb throughout life, but it remains unknown whether the properties of new neurons generated in newborn animals differ from those added during adulthood. We compared the densities of glutamatergic synapses of granule cells (GCs) generated in newborn and adult rats over extended periods of time. We observed that, whereas adult-born GCs maintained stable cell-to-cell variability of synaptic densities soon after they integrated into the circuit, cell-to-cell variability of synaptic densities of neonatal-born GCs increased months after their integration. We also investigated whether the synaptic reorganization induced by sensory deprivation occurred differently in …


Human-Specific Histone Methylation Signatures At Transcription Start Sites In Prefrontal Neurons, Hennady Shulha, Jessica Crisci, Denis Reshetov, Jogender Tushir, Iris Cheung, Rahul Bharadwaj, Hsin-Jung Chou, Isaac Houston, Cyril Peter, Amanda Mitchell, Wei-Dong Yao, Richard Myers, Jiang-Fan Chen, Todd Preuss, Evgeny Rogaev, Jeffrey Jensen, Zhiping Weng, Schahram Akbarian Apr 2013

Human-Specific Histone Methylation Signatures At Transcription Start Sites In Prefrontal Neurons, Hennady Shulha, Jessica Crisci, Denis Reshetov, Jogender Tushir, Iris Cheung, Rahul Bharadwaj, Hsin-Jung Chou, Isaac Houston, Cyril Peter, Amanda Mitchell, Wei-Dong Yao, Richard Myers, Jiang-Fan Chen, Todd Preuss, Evgeny Rogaev, Jeffrey Jensen, Zhiping Weng, Schahram Akbarian

Hsin-Jung Chou

Cognitive abilities and disorders unique to humans are thought to result from adaptively driven changes in brain transcriptomes, but little is known about the role of cis-regulatory changes affecting transcription start sites (TSS). Here, we mapped in human, chimpanzee, and macaque prefrontal cortex the genome-wide distribution of histone H3 trimethylated at lysine 4 (H3K4me3), an epigenetic mark sharply regulated at TSS, and identified 471 sequences with human-specific enrichment or depletion. Among these were 33 loci selectively methylated in neuronal but not non-neuronal chromatin from children and adults, including TSS at DPP10 (2q14.1), CNTN4 and CHL1 (3p26.3), and other neuropsychiatric susceptibility …


Dsarm/Sarm1 Is Required For Activation Of An Injury-Induced Axon Death Pathway, Jeannette Osterloh, Jing Yang, Timothy Rooney, A. Fox, Robert Adalbert, Eric Powell, Amy Sheehan, Michelle Avery, Rachel Hackett, Mary Logan, Jennifer Macdonald, Jennifer Ziegenfuss, Stefan Milde, Ying-Ju Hou, Carl Nathan, Aihao Ding, Robert Brown, Laura Comforti, Michael Coleman, Marc Tessier-Lavigne, Stephan Zuchner, Marc Freeman Dec 2012

Dsarm/Sarm1 Is Required For Activation Of An Injury-Induced Axon Death Pathway, Jeannette Osterloh, Jing Yang, Timothy Rooney, A. Fox, Robert Adalbert, Eric Powell, Amy Sheehan, Michelle Avery, Rachel Hackett, Mary Logan, Jennifer Macdonald, Jennifer Ziegenfuss, Stefan Milde, Ying-Ju Hou, Carl Nathan, Aihao Ding, Robert Brown, Laura Comforti, Michael Coleman, Marc Tessier-Lavigne, Stephan Zuchner, Marc Freeman

Dr Robert Brown

Axonal and synaptic degeneration is a hallmark of peripheral neuropathy, brain injury, and neurodegenerative disease. Axonal degeneration has been proposed to be mediated by an active autodestruction program, akin to apoptotic cell death; however, loss-of-function mutations capable of potently blocking axon self-destruction have not been described. Here, we show that loss of the Drosophila Toll receptor adaptor dSarm (sterile alpha/Armadillo/Toll-Interleukin receptor homology domain protein) cell-autonomously suppresses Wallerian degeneration for weeks after axotomy. Severed mouse Sarm1 null axons exhibit remarkable long-term survival both in vivo and in vitro, indicating that Sarm1 prodegenerative signaling is conserved in mammals. Our results provide direct …