Browsing by Author "Scharff, Constance"

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    A molecular neuroethological approach for identifying and characterizing a cascade of behaviorally regulated genes.
    (Proc Natl Acad Sci U S A, 2006-10-10) Wada, Kazuhiro; Howard, Jason T; McConnell, Patrick; Whitney, Osceola; Lints, Thierry; Rivas, Miriam V; Horita, Haruhito; Patterson, Michael A; White, Stephanie A; Scharff, Constance; Haesler, Sebastian; Zhao, Shengli; Sakaguchi, Hironobu; Hagiwara, Masatoshi; Shiraki, Toshiyuki; Hirozane-Kishikawa, Tomoko; Skene, Pate; Hayashizaki, Yoshihide; Carninci, Piero; Jarvis, Erich D
    Songbirds have one of the most accessible neural systems for the study of brain mechanisms of behavior. However, neuroethological studies in songbirds have been limited by the lack of high-throughput molecular resources and gene-manipulation tools. To overcome these limitations, we constructed 21 regular, normalized, and subtracted full-length cDNA libraries from brains of zebra finches in 57 developmental and behavioral conditions in an attempt to clone as much of the brain transcriptome as possible. From these libraries, approximately 14,000 transcripts were isolated, representing an estimated 4,738 genes. With the cDNAs, we created a hierarchically organized transcriptome database and a large-scale songbird brain cDNA microarray. We used the arrays to reveal a set of 33 genes that are regulated in forebrain vocal nuclei by singing behavior. These genes clustered into four anatomical and six temporal expression patterns. Their functions spanned a large range of cellular and molecular categories, from signal transduction, trafficking, and structural, to synaptically released molecules. With the full-length cDNAs and a lentiviral vector system, we were able to overexpress, in vocal nuclei, proteins of representative singing-regulated genes in the absence of singing. This publicly accessible resource http://songbirdtranscriptome.net can now be used to study molecular neuroethological mechanisms of behavior.
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    Basal ganglia function, stuttering, sequencing, and repair in adult songbirds.
    (Sci Rep, 2014-10-13) Kubikova, Lubica; Bosikova, Eva; Cvikova, Martina; Lukacova, Kristina; Scharff, Constance; Jarvis, Erich D
    A pallial-basal-ganglia-thalamic-pallial loop in songbirds is involved in vocal motor learning. Damage to its basal ganglia part, Area X, in adult zebra finches has been noted to have no strong effects on song and its function is unclear. Here we report that neurotoxic damage to adult Area X induced changes in singing tempo and global syllable sequencing in all animals, and considerably increased syllable repetition in birds whose song motifs ended with minor repetitions before lesioning. This stuttering-like behavior started at one month, and improved over six months. Unexpectedly, the lesioned region showed considerable recovery, including immigration of newly generated or repaired neurons that became active during singing. The timing of the recovery and stuttering suggest that immature recovering activity of the circuit might be associated with stuttering. These findings indicate that even after juvenile learning is complete, the adult striatum plays a role in higher level organization of learned vocalizations.
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    FoxP2 expression in avian vocal learners and non-learners.
    (J Neurosci, 2004-03-31) Haesler, Sebastian; Wada, Kazuhiro; Nshdejan, A; Morrisey, Edward E; Lints, Thierry; Jarvis, Eric D; Scharff, Constance
    Most vertebrates communicate acoustically, but few, among them humans, dolphins and whales, bats, and three orders of birds, learn this trait. FOXP2 is the first gene linked to human speech and has been the target of positive selection during recent primate evolution. To test whether the expression pattern of FOXP2 is consistent with a role in learned vocal communication, we cloned zebra finch FoxP2 and its close relative FoxP1 and compared mRNA and protein distribution in developing and adult brains of a variety of avian vocal learners and non-learners, and a crocodile. We found that the protein sequence of zebra finch FoxP2 is 98% identical with mouse and human FOXP2. In the avian and crocodilian forebrain, FoxP2 was expressed predominantly in the striatum, a basal ganglia brain region affected in patients with FOXP2 mutations. Strikingly, in zebra finches, the striatal nucleus Area X, necessary for vocal learning, expressed more FoxP2 than the surrounding tissue at post-hatch days 35 and 50, when vocal learning occurs. In adult canaries, FoxP2 expression in Area X differed seasonally; more FoxP2 expression was associated with times when song becomes unstable. In adult chickadees, strawberry finches, song sparrows, and Bengalese finches, Area X expressed FoxP2 to different degrees. Non-telencephalic regions in both vocal learning and non-learning birds, and in crocodiles, were less variable in expression and comparable with regions that express FOXP2 in human and rodent brains. We conclude that differential expression of FoxP2 in avian vocal learners might be associated with vocal plasticity.
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    The genome of a songbird.
    (Nature, 2010-04-01) Warren, Wesley C; Clayton, David F; Ellegren, Hans; Arnold, Arthur P; Hillier, Ladeana W; Künstner, Axel; Searle, Steve; White, Simon; Vilella, Albert J; Fairley, Susan; Heger, Andreas; Kong, Lesheng; Ponting, Chris P; Jarvis, Erich D; Mello, Claudio V; Minx, Pat; Lovell, Peter; Velho, Tarciso AF; Ferris, Margaret; Balakrishnan, Christopher N; Sinha, Saurabh; Blatti, Charles; London, Sarah E; Li, Yun; Lin, Ya-Chi; George, Julia; Sweedler, Jonathan; Southey, Bruce; Gunaratne, Preethi; Watson, Michael; Nam, Kiwoong; Backström, Niclas; Smeds, Linnea; Nabholz, Benoit; Itoh, Yuichiro; Whitney, Osceola; Pfenning, Andreas R; Howard, Jason; Völker, Martin; Skinner, Bejamin M; Griffin, Darren K; Ye, Liang; McLaren, William M; Flicek, Paul; Quesada, Victor; Velasco, Gloria; Lopez-Otin, Carlos; Puente, Xose S; Olender, Tsviya; Lancet, Doron; Smit, Arian FA; Hubley, Robert; Konkel, Miriam K; Walker, Jerilyn A; Batzer, Mark A; Gu, Wanjun; Pollock, David D; Chen, Lin; Cheng, Ze; Eichler, Evan E; Stapley, Jessica; Slate, Jon; Ekblom, Robert; Birkhead, Tim; Burke, Terry; Burt, David; Scharff, Constance; Adam, Iris; Richard, Hugues; Sultan, Marc; Soldatov, Alexey; Lehrach, Hans; Edwards, Scott V; Yang, Shiaw-Pyng; Li, Xiaoching; Graves, Tina; Fulton, Lucinda; Nelson, Joanne; Chinwalla, Asif; Hou, Shunfeng; Mardis, Elaine R; Wilson, Richard K
    The zebra finch is an important model organism in several fields with unique relevance to human neuroscience. Like other songbirds, the zebra finch communicates through learned vocalizations, an ability otherwise documented only in humans and a few other animals and lacking in the chicken-the only bird with a sequenced genome until now. Here we present a structural, functional and comparative analysis of the genome sequence of the zebra finch (Taeniopygia guttata), which is a songbird belonging to the large avian order Passeriformes. We find that the overall structures of the genomes are similar in zebra finch and chicken, but they differ in many intrachromosomal rearrangements, lineage-specific gene family expansions, the number of long-terminal-repeat-based retrotransposons, and mechanisms of sex chromosome dosage compensation. We show that song behaviour engages gene regulatory networks in the zebra finch brain, altering the expression of long non-coding RNAs, microRNAs, transcription factors and their targets. We also show evidence for rapid molecular evolution in the songbird lineage of genes that are regulated during song experience. These results indicate an active involvement of the genome in neural processes underlying vocal communication and identify potential genetic substrates for the evolution and regulation of this behaviour.