Claudio Mello
Oregon Health & Science University, Behavioral Neuroscience, Faculty Member
Research Interests:
Research Interests:
A Correction to this paper has been published: https://doi.org/10.1038/s41586-021-03473-8.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests: Neuroscience, Biology, Neurotransmission, Medicine, Comparative Physiology, and 14 moreBiological Sciences, Female, Animals, Male, Synaptic Transmission, Zebra finch, Auditory Cortex, Action Potentials, Glutamic Acid, Bursting, Acoustic Stimulation, Gabaergic, Finches, and Medical and Health Sciences
The low-density lipoprotein receptor (LDLR) is key to cellular cholesterol uptake and is also the main receptor for the vesicular stomatitis virus glycoprotein (VSV G). Here we show that in songbirds LDLR is highly divergent and lacks... more
The low-density lipoprotein receptor (LDLR) is key to cellular cholesterol uptake and is also the main receptor for the vesicular stomatitis virus glycoprotein (VSV G). Here we show that in songbirds LDLR is highly divergent and lacks domains critical for ligand binding and cellular trafficking, inconsistent with universal structure conservation and function across vertebrates. Linked to the LDLR functional domain loss, zebra finches show inefficient infectivity by lentiviruses (LVs) pseudotyped with VSV G, which can be rescued by the expression of human LDLR. Finches also show an atypical plasma lipid distribution that relies largely on high-density lipoprotein (HDL). These findings provide insights into the genetics and evolution of viral infectivity and cholesterol transport mechanisms in vertebrates.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
How the evolution of complex behavioral traits is associated with the emergence of novel brain pathways is largely unknown. Songbirds, like humans, learn vocalizations via tutor imitation and possess a specialized brain circuitry to... more
How the evolution of complex behavioral traits is associated with the emergence of novel brain pathways is largely unknown. Songbirds, like humans, learn vocalizations via tutor imitation and possess a specialized brain circuitry to support this behavior. In a comprehensive in situ hybridization effort, we show that the zebra finch vocal robust nucleus of the arcopallium (RA) shares numerous markers (e.g. SNCA, PVALB) with the adjacent dorsal intermediate arcopallium (AId), an avian analog of mammalian deep cortical layers with involvement in motor function. We also identify markers truly unique to RA and thus likely linked to modulation of vocal motor function (e.g. KCNC1, GABRE), including a subset of the known shared markers between RA and human laryngeal motor cortex (e.g. SLIT1, RTN4R, LINGO1, PLXNC1). The data provide novel insights into molecular features unique to vocal learning circuits, and lend support for the motor theory for vocal learning origin.
Research Interests:
Research Interests:
Page 1. 17 Isolation of Song-Regulated Genes in the Brain of Songbirds Claudio V. Mello, Erich D. Jarvis, Natalia Denisenko, and Miriam Rivas 1. Introduction ... 9. Klenow DNA polymerase (NewEngland BioLabs, Beverly, MA), 2 U/pL, and... more
Page 1. 17 Isolation of Song-Regulated Genes in the Brain of Songbirds Claudio V. Mello, Erich D. Jarvis, Natalia Denisenko, and Miriam Rivas 1. Introduction ... 9. Klenow DNA polymerase (NewEngland BioLabs, Beverly, MA), 2 U/pL, and Klenow buffer. 2.6. ...
Research Interests:
Research Interests:
Research Interests:
Among its various roles as a micronutrient, vitamin A (vit. A; retinol) is necessary for juvenile brain development and maintenance of adult neuronal phenotypes. Metabolism of vit. A produces all-trans retinoic acid (ATRA), which is... more
Among its various roles as a micronutrient, vitamin A (vit. A; retinol) is necessary for juvenile brain development and maintenance of adult neuronal phenotypes. Metabolism of vit. A produces all-trans retinoic acid (ATRA), which is unique as a diet-derived activator of transcription factors: the re...
Research Interests:
The underlying mechanisms that promote precise spiking in upper motor neurons controlling fine motor skills are not well understood. Here we report that projection neurons in the adult zebra finch song nucleus RA display: 1) robust... more
The underlying mechanisms that promote precise spiking in upper motor neurons controlling fine motor skills are not well understood. Here we report that projection neurons in the adult zebra finch song nucleus RA display: 1) robust high-frequency firing, 2) ultra-short half-width spike waveforms, 3) superfast Na+ current inactivation kinetics and 4) large resurgent Na+ currents (INaR). These spiking properties closely resemble those of specialized pyramidal neurons in mammalian motor cortex and are well suited for precise temporal coding. They emerge during the critical period for vocal learning in males but not females, coinciding with a complete switch of modulatory Na+ channel subunit expression from Navβ3 to Navβ4. Dynamic clamping and dialysis of Navβ4’s C-terminal peptide into juvenile RA neurons provide evidence that this subunit, and its associated INaR, promote neuronal excitability. We propose that Navβ4 underpins INaR that facilitates precise, prolonged, and reliable high...
Research Interests:
Research Interests:
Research Interests:
Research Interests:
This dataset contains a set of MS Excel tables in single .xlsx files, that document the curation of a large set of oligonucleotide (oligo) annotations from the Agilent Songbird Oligonucleotide Array V2.<br><b>Table 2</b>... more
This dataset contains a set of MS Excel tables in single .xlsx files, that document the curation of a large set of oligonucleotide (oligo) annotations from the Agilent Songbird Oligonucleotide Array V2.<br><b>Table 2</b> summarizes the overall effort, and provides a summary breakdown of the sets of oligos analyzed in the study. Summary data include total number of oligos examined, total that passed genomic filters and those removed for further analysis (including reasoning), along with total numbers of valid oligos either analyzed further or not.<br><b>Tables 3-13</b> provide a list of subsets of oligos that were curated at each step of the analysis, including subsets of oligos that were removed because they were deemed uninformative (<b>Tables 3-6</b>), or subjected to a name verification and/or reannotation effort (<b>Tables 8-13</b>). The step-by-step curation of these oligos is described in the manuscript associated with this dataset.<br>Oligos in various categories are identified by 'oligo IDs' given by Duke University. Those subject to name verification and/or reannotation effort also have recorded the most recent oligo consensus symbols and names applied in two studies referenced in the related paper, Chromosomal and strand information to which the oligo aligns, and related HGNC ID Gene Description and HGNC Symbol Status, where relevant.<br><b>Background</b>Zebra finches are a major model organism for investigating mechanisms of vocal learning, a trait that enables spoken language in humans. The development of EST/cDNA database collections and microarrays has allowed extensive molecular characterizations of the vocal learning and production circuitry. However, poor curation of these databases can lead to errors in transcriptome and bioinformatics analyses, limiting the impact of these resources. Here we used genomic alignments and synteny analysis for orthology verification to curate and reannotate a large set of oligonucleotides and corresponding ESTs/cDNAs that make-up Agilent microarrays for gene expres [...]
High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are only available for a few non-microbial species1–4. To... more
High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are only available for a few non-microbial species1–4. To address this issue, the international Genome 10K (G10K) consortium5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling the most accurate and complete reference genomes to date. Here we summarize these developments, introduce a set of quality standards, and present lessons learned from sequencing and assembling 16 species representing major vertebrate lineages (mammals, birds, reptiles, amphibians, teleost fishes and cartilaginous fishes). We confirm that long-read sequencing technologies are essential for maximizing genome quality and that unresolved complex repeats and haplotype heterozygosity are major sources of error in assemblies. Our new assemblies identify and correct substantial errors in some o...
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Spinal circuitry that enables wing flapping in birds evolved via genetic alternations of a guidance molecule. Flight in birds evolved through patterning of the wings from forelimbs and transition from alternating gait to synchronous... more
Spinal circuitry that enables wing flapping in birds evolved via genetic alternations of a guidance molecule. Flight in birds evolved through patterning of the wings from forelimbs and transition from alternating gait to synchronous flapping. In mammals, the spinal midline guidance molecule ephrin-B3 instructs the wiring that enables limb alternation, and its deletion leads to synchronous hopping gait. Here, we show that the ephrin-B3 protein in birds lacks several motifs present in other vertebrates, diminishing its affinity for the EphA4 receptor. The avian ephrin-B3 gene lacks an enhancer that drives midline expression and is missing in galliforms. The morphology and wiring at brachial levels of the chicken embryonic spinal cord resemble those of ephrin-B3 null mice. Dorsal midline decussation, evident in the mutant mouse, is apparent at the chick brachial level and is prevented by expression of exogenous ephrin-B3 at the roof plate. Our findings support a role for loss of ephrin-B3 function in shaping the avian brachial spinal cord circuitry and facilitating synchronous wing flapping.
Research Interests:
While the analysis of Bornelöv et al. is informative, they provide evidence for the existence of only 3% of the reported avian missing genes set, and thus do not significantly challenge our main findings that specific groups of syntenic... more
While the analysis of Bornelöv et al. is informative, they provide evidence for the existence of only 3% of the reported avian missing genes set, and thus do not significantly challenge our main findings that specific groups of syntenic protein-coding genes are missing in birds.This is a response to the Correspondence article: https://www.dx.doi.org/10.1186/s13059-017-1231-1.
Research Interests:
Research Interests: Motor Control, Gene expression, Animal communication, Comparative Physiology, Biological Sciences, and 15 moreBrain Mapping, Brain, Animals, Neuronal Plasticity, Songbirds, Comparative Analysis, Neural plasticity, High Resolution, Long Term Memory, Species Specificity, Focal Point, DNA binding proteins, Motor activity, Medical and Health Sciences, and Expression pattern
Research Interests:
In the present study, immunocytochemistry was used to assess the expression of Egr-1 nuclear protein across selected regions of the opossum visual system. In light-deprived (LD) animals, only a few scattered cell nuclei were found... more
In the present study, immunocytochemistry was used to assess the expression of Egr-1 nuclear protein across selected regions of the opossum visual system. In light-deprived (LD) animals, only a few scattered cell nuclei were found throughout the striate cortex (V1). Exposure to light promoted a significant increase in the density of Egr-1 labeled nuclei in V1. Laminar distribution of immunoreactive nuclei in light-stimulated animals (LS) tended to vary with topography: the lateral region, which corresponds to the central representation of the visual field, appeared to have higher density of cells expressing protein in the supragranular layers, as compared to the medial region, which corresponds to the representation of the peripheral field of vision. Finally, LS animals displayed a narrow band of labeled cell nuclei in the intergeniculate leaflet (IGL) and throughout the anteroposterior extent of the superior colliculus (SC). In contrast, almost no Egr-1 immunolabeling was found in the IGL and SC of LD animals. Our report is the first demonstration of light-regulated expression of the Egr-1 gene in the opossum visual system and provides evidence that the expression of an activity-dependent gene related to neural plasticity is evolutionarily conserved in the visual cortex of the mammalian lineage.
Research Interests: Cognitive Science, Immunohistochemistry, Transcription Factors, Visual Cortex, Brain Mapping, and 15 moreBrain, Topography, Animals, Male, Light, Superior Colliculus, Neural plasticity, Sensory Deprivation, Neural pathways, Visual Field, Opossums, DNA binding proteins, Neurosciences, Striate Cortex, and photic stimulation
Central neurons express a variety of neuronal types and ion channels that promote firing heterogeneity among their distinct neuronal populations. Action potential (AP) phasic firing, produced by low-threshold voltage-activated potassium... more
Central neurons express a variety of neuronal types and ion channels that promote firing heterogeneity among their distinct neuronal populations. Action potential (AP) phasic firing, produced by low-threshold voltage-activated potassium currents (VAKCs), is commonly observed in mammalian brainstem neurons involved in the processing of temporal properties of the acoustic information. The avian caudomedial nidopallium (NCM) is an auditory area analogous to portions of the mammalian auditory cortex that is involved in the perceptual discrimination and memorization of birdsong and shows complex responses to auditory stimuli We performed in vitro whole-cell patch-clamp recordings in brain slices from adult zebra finches (Taeniopygia guttata) and observed that half of NCM neurons fire APs phasically in response to membrane depolarizations, while the rest fire transiently or tonically. Phasic neurons fired APs faster and with more temporal precision than tonic and transient neurons. These ...
ABSTRACT At present, there are three independent lineages of birds—songbirds, parrots, and hummingbirds—that are known to learn their vocalizations. Each of these clades possesses a &#39;song circuit,&#39; a system of... more
ABSTRACT At present, there are three independent lineages of birds—songbirds, parrots, and hummingbirds—that are known to learn their vocalizations. Each of these clades possesses a &#39;song circuit,&#39; a system of interconnected forebrain nuclei that control this vocal learning behavior. The anatomical, physiological, and (to a lesser extent) molecular features of the songbird song circuit have been extensively characterized, but it is unclear which of these features represent neuronal requirements of song circuits that are common to all vocal learning birds, and which constitute specializations unique to songbirds. Of particular interest is HVC, the main pre-motor input to the vocal-motor output nucleus (RA) as well as the source of descending input to Area X, the basal ganglia component of a ‘cortico’-striato-thalamo-‘cortical’ loop crucial for song learning. Although parrot and hummingbird equivalents of songbird HVC, RA, and Area X have been identified, it is unclear which elements of these nuclei (e.g., interconnections, cell types, and expressed transcripts) may be conserved or convergent among vocal learning birds. To address this possibility, we sought to identify molecular markers—transcripts uniquely expressed in specific cell-type populations—that may differentiate analogous or homologous cell types in the song circuits of Zebra Finch (Taeniopygia guttata), Budgerigar (Melopsittacus undulatus), and Anna&#39;s Hummingbird (Calypte anna). We first compared results from microarray experiments conducted in HVC and its hummingbird equivalent to identify candidate markers likely to be conserved in all vocal learning birds. We then used in situ hybridization studies to investigate the expression of these markers in all three lineages. Our results indicate that some genes showed remarkably conserved patterns of expression in all three groups, pointing to conserved molecular programs in the equivalents of GABAergic interneurons and HVC-to-RA projection neurons. In contrast, markers of HVC-to-Area X projection neurons were largely not conserved. Together, these results point to molecular requirements for vocal learning in birds, but also suggest that there may be specific differences that reflect multiple evolutionary solutions to the problem of building a song circuit in the evolutionary histories of these groups.
Among known bird species, oscines are one of the few groups that produce complex vocalizations due to vocal learning. One of the most conspicuous oscine passerines in southeastern South America is the Rufous-bellied Thrush, Turdus... more
Among known bird species, oscines are one of the few groups that produce complex vocalizations due to vocal learning. One of the most conspicuous oscine passerines in southeastern South America is the Rufous-bellied Thrush, Turdus rufiventris. The complete mitochondrial genome of this species was sequenced with the Illumina HiSeq platform (Illumina Inc., San Diego, CA), assembled using MITObim software and annotated by MITOS web server and Artemis software. This mitogenome contained 16 669 bases, organized as 13 protein-coding genes, 22 transfer RNAs, two ribosomal RNAs, and a control region (d-loop). The sequencing of the Rufous-bellied Thrush mitochondrial genome is of particular interest for better understanding of population genetics and phylogeography of the Turdidae family.
Research Interests:
Research Interests:
Songbirds are capable of learning their vocalizations by copying a singing adult. This vocal learning ability requires juveniles to hear and memorize the sound of the adult song, and later to imitate it through a process involving... more
Songbirds are capable of learning their vocalizations by copying a singing adult. This vocal learning ability requires juveniles to hear and memorize the sound of the adult song, and later to imitate it through a process involving sensorimotor integration. Vocal learning is a trait that songbirds share with humans, where it forms the basis of spoken language acquisition, with other avian groups (parrots and hummingbirds), and with a few other mammals (cetaceans, bats). It is however absent in traditional model organisms such as rodents and nonhuman primates. Zebra finches, a songbird species from Australia, are popular pets and are easy to breed. They also sing a relatively simple and stereotyped song that is amenable to quantitative analysis. Zebra finches have thus emerged as a choice model organism for investigating the neurobiological basis of vocal learning. A number of tools and methodologies have been developed to characterize the bioacoustics properties of their song, analyz...
Research Interests:
High-throughput methods for analyzing genome structure and function are having a large impact in songbird neurobiology. Methods include genome sequencing and annotation, comparative genomics, DNA microarrays and transcriptomics, and the... more
High-throughput methods for analyzing genome structure and function are having a large impact in songbird neurobiology. Methods include genome sequencing and annotation, comparative genomics, DNA microarrays and transcriptomics, and the development of a brain atlas of gene expression. Key emerging findings include the identification of complex transcriptional programs active during singing, the robust brain expression of non-coding RNAs, evidence of profound variations in gene expression across brain regions, and the identification of molecular specializations within song production and learning circuits. Current challenges include the statistical analysis of large datasets, effective genome curations, the efficient localization of gene expression changes to specific neuronal circuits and cells, and the dissection of behavioral and environmental factors that influence brain gene expression. The field requires efficient methods for comparisons with organisms like chicken, which offer...
Research Interests:
The ZENK gene encodes a zinc-finger-containing transcriptional regulator and can be rapidly activated in songbird brain by presentation of birdsong (Mello et al., 1992). Here we map the areas of the songbird forebrain that show this... more
The ZENK gene encodes a zinc-finger-containing transcriptional regulator and can be rapidly activated in songbird brain by presentation of birdsong (Mello et al., 1992). Here we map the areas of the songbird forebrain that show this genomic response to birdsong, using in situ hybridization. After 30 min of song presentation ZENK mRNA levels reach a peak in the caudomedial telencephalon, in areas adjacent to or closely related with primary auditory structures. These areas include subfields of field L (L1 and L3), the caudomedial neostriatum (NCM), the caudomedial hyperstriatum ventrale (CMHV) anterior to field L, the caudal paleostriatum, and two field L targets, HVC shelf and RA cup. In contrast, ZENK induction is absent in some areas that show a response to song by other measures and where ZENK induction might have been expected. These include the direct thalamo-recipient field L subfield L2, and the nuclei of the circuit involved in the acquisition and production of learned song. ...
Research Interests:
Research Interests: Physiology, Long Term Potentiation, Gene expression, Prefrontal Cortex, Biological Sciences, and 15 moreHippocampus, Animals, Corticosterone, Male, Parietal Cortex, EST, Microarray Analysis, LTP, Protein Kinase, qRT PCR, Functional Laterality, Nras, Psychology and Cognitive Sciences, JAK, and Medical and Health Sciences
Many of the assumptions of homology on which the standard nomenclature for the cell groups and fiber tracts of avian brains have been based are in error, and as a result that terminology promotes misunderstanding of the functional... more
Many of the assumptions of homology on which the standard nomenclature for the cell groups and fiber tracts of avian brains have been based are in error, and as a result that terminology promotes misunderstanding of the functional organization of avian brains and their evolutionary relationship to mammalian brains. Recognizing this problem, a number of avian brain researchers began an effort to revise the terminology, which culminated in the Avian Brain Nomenclature Forum, held at Duke University from July 18 to 20, 2002. In the new terminology approved at this Forum, the flawed conception that the telencephalon of birds consists nearly entirely of a hypertrophied basal ganglia has been purged from the telencephalic terminology, and the actual parts of the basal ganglia and its brainstem afferent cell groups have been given names reflecting their now evident homologies. The telencephalic regions that were erroneously named to reflect presumed homology to mammalian basal ganglia were...