Navegando por Autor "Mello, Claudio V."

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Hippocampal functional organization: a microstructure of the place cell network encoding space
(2019-04-06) Pavlides, Constantine; Donishi, Tomohiro; Ribeiro, Sidarta Tollendal Gomes; Mello, Claudio V.; Blanco, Wilfredo; Ogawa, Sonoko
A clue to hippocampal function has been the discovery of place cells, leading to the ‘spatial map’ theory. Although the firing attributes of place cells are well documented, little is known about the organization of the spatial map. Unit recording studies, thus far, have reported a low coherence between neighboring cells and geometric space, leading to the prevalent view that the spatial map is not topographically organized. However, the number of simultaneously recorded units is severely limited, rendering construction of the spatial map nearly impossible. To visualize the functional organization of place cells, we used the activity-dependent immediate-early gene Zif268 in combination with behavioral, pharmacological and electrophysiological methods, in mice and rats exploring an environment. Here, we show that in animals confined to a small part of a maze, principal cells in the CA1/CA3 subfields of the dorsal hippocampus immunoreactive (IR) for Zif268 adhere to a ‘cluster-type’ organization. Unit recordings confirmed that the Zif268 IR clusters correspond to active place cells, while blockade of NMDAR (which alters place fields) disrupted the Zif268 IR clusters. Contrary to the prevalent view that the spatial map consists of a non-topographic neural network, our results provide evidence for a ‘cluster-type’ functional organization of hippocampal neurons encoding for space.
Identification and characterization of primordial germ cells in a vocal learning Neoaves species, the zebra finch
(Wiley, 2019-10-11) Jung, Kyung Min; Kim, Young Min; Keyte, Anna L.; Biegler, Matthew T.; Rengaraj, Deivendran; Lee, Hong Jo; Mello, Claudio V.; Velho, Tarciso André Ferreira; Fedrigo, Olivier; Haase, Bettina; Jarvis, Erich D.; Han, Jae Yong
The zebra finch has been used as a valuable vocal learning animal model for human spoken language. It is representative of vocal learning songbirds specifically, which comprise half of all bird species, and of Neoaves broadly, which comprise 95% of all bird species. Although transgenesis in the zebra finch has been accomplished, it is with a very low efficiency of germ-line transmission and far from the efficiency with a more genetically tractable but vocal nonlearning species, the chicken (a Galloanseriformes). To improve germ-line transmission in the zebra finch, we identified and characterized its primordial germ cells (PGCs) and compared them with chicken. We found striking differences between the 2 species, including that zebra finch PGCs were more numerous, more widely distributed in early embryos before colonization into the gonads, had slower timing of colonization, and had a different developmental gene-expression program. We improved conditions for isolating and culturing zebra finch PGCs in vitro and were able to transfect them with gene-expression vectors and incorporate them into the gonads of host embryos. Our findings demonstrate important differences in the PGCs of the zebra finch and advance the first stage of creating PGC-mediated germ-line transgenics of a vocal learning species.
Noradrenergic Control of Gene Expression and Long- Term Neuronal Adaptation Evoked by Learned Vocalizations in Songbirds
(2012-05-04) Velho, Tarciso André Ferreira; Lu, Kai; Ribeiro, Sidarta Tollendal Gomes; Pinaud, Raphael; Vicario, David; Mello, Claudio V.
Norepinephrine (NE) is thought to play important roles in the consolidation and retrieval of long-term memories, but its role in the processing and memorization of complex acoustic signals used for vocal communication has yet to be determined. We have used a combination of gene expression analysis, electrophysiological recordings and pharmacological manipulations in zebra finches to examine the role of noradrenergic transmission in the brain’s response to birdsong, a learned vocal behavior that shares important features with human speech. We show that noradrenergic transmission is required for both the expression of activity-dependent genes and the long-term maintenance of stimulus-specific electrophysiological adaptation that are induced in central auditory neurons by stimulation with birdsong. Specifically, we show that the caudomedial nidopallium (NCM), an area directly involved in the auditory processing and memorization of birdsong, receives strong noradrenergic innervation. Song-responsive neurons in this area express a-adrenergic receptors and are in close proximity to noradrenergic terminals. We further show that local a-adrenergic antagonism interferes with song-induced gene expression, without affecting spontaneous or evoked electrophysiological activity, thus dissociating the molecular and electrophysiological responses to song. Moreover, a-adrenergic antagonism disrupts the maintenance but not the acquisition of the adapted physiological state. We suggest that the noradrenergic system regulates long-term changes in song-responsive neurons by modulating the gene expression response that is associated with the electrophysiological activation triggered by song. We also suggest that this mechanism may be an important contributor to long-term auditory memories of learned vocalizations.
The genomic response to song and the representation of complex sounds in the auditory system of zebra finches
(2008-06) Velho, Tarciso André Ferreira; Mello, Claudio V.
The consolidation of long-lasting sensory memories requires the activation of gene expression programs. However, to fully understand the contribution of genomic events necessary for sensory learning, it is necessary to characterize the components involved in this response, their induction kinetics, and the possible functional interactions among individual components. Birdsong represents one of the best natural behaviors to study gene expression induced by auditory stimulation in awake, freely behaving animals. The present work addresses the properties and functional consequences of the genomic response to birdsong in zebra finches (Taeniopygia guttata), with a specific focus on the caudomedial nidopallium (NCM), a cortical-like auditory area involved in song auditory processing and memorization. We found that song induces a wellorchestrated cascade of gene expression that includes early and late genes. Early genes are co-expressed by NCM neurons and their induction is regulated by the mitogen-activated protein (MAP) kinase pathway. In addition, we also found that the induction of early genes is locally modulated by norepinephrine. We have also identified two late genes, syn2 and syn3, whose induction is repressed by early song-induced proteins genes in NCM. Functionally, we show that blockade of this response by α-adrenergic antagonists disrupts the long-term maintenance of long-lasting neuronal changes triggered by song. Finally, we show that the pattern of early song-induce gene expression in NCM is stimulus dependent. These patterns also indicate the existence of functional subdomains of more or less selectivity towards conspecific songs. Overall, these results help us understand the functional significance of the genomic response to song and the functional organization of sound representation in a higher order auditory area of the songbird brain.

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Navegando por Autor "Mello, Claudio V."