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1.
Nature ; 612(7939): 316-322, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36450986

RESUMO

In neural networks that store information in their connection weights, there is a tradeoff between sensitivity and stability1,2. Connections must be plastic to incorporate new information, but if they are too plastic, stored information can be corrupted. A potential solution is to allow plasticity only during epochs when task-specific information is rich, on the basis of a 'when-to-learn' signal3. We reasoned that dopamine provides a when-to-learn signal that allows the brain's spatial maps to update when new spatial information is available-that is, when an animal is moving. Here we show that the dopamine neurons innervating the Drosophila head direction network are specifically active when the fly turns to change its head direction. Moreover, their activity scales with moment-to-moment fluctuations in rotational speed. Pairing dopamine release with a visual cue persistently strengthens the cue's influence on head direction cells. Conversely, inhibiting these dopamine neurons decreases the influence of the cue. This mechanism should accelerate learning during moments when orienting movements are providing a rich stream of head direction information, allowing learning rates to be low at other times to protect stored information. Our results show how spatial learning in the brain can be compressed into discrete epochs in which high learning rates are matched to high rates of information intake.


Assuntos
Dopamina
3.
Mamm Genome ; 29(5-6): 325-343, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29737391

RESUMO

To fine map a mouse QTL for lean body mass (Burly1), we used information from intercross, backcross, consomic, and congenic mice derived from the C57BL/6ByJ (host) and 129P3/J (donor) strains. The results from these mapping populations were concordant and showed that Burly1 is located between 151.9 and 152.7 Mb (rs33197365 to rs3700604) on mouse chromosome 2. The congenic region harboring Burly1 contains 26 protein-coding genes, 11 noncoding RNA elements (e.g., lncRNA), and 4 pseudogenes, with 1949 predicted functional variants. Of the protein-coding genes, 7 have missense variants, including genes that may contribute to lean body weight, such as Angpt41, Slc52c3, and Rem1. Lean body mass was increased by the B6-derived variant relative to the 129-derived allele. Burly1 influenced lean body weight at all ages but not food intake or locomotor activity. However, congenic mice with the B6 allele produced more heat per kilogram of lean body weight than did controls, pointing to a genotype effect on lean mass metabolism. These results show the value of integrating information from several mapping populations to refine the map location of body composition QTLs and to identify a short list of candidate genes.


Assuntos
Mapeamento Cromossômico , Cromossomos de Mamíferos , Locos de Características Quantitativas , Característica Quantitativa Herdável , Magreza/genética , Fatores Etários , Animais , Mapeamento Cromossômico/métodos , Cruzamentos Genéticos , Metabolismo Energético/genética , Feminino , Estudos de Associação Genética , Variação Genética , Genótipo , Masculino , Camundongos , Magreza/metabolismo
4.
Ecology ; 95(1): 9-13, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24649640

RESUMO

Insect mutualisms can have disproportionately large impacts on local arthropod and plant communities and their responses to climatic change. The objective of this study was to determine if the presence of insect mutualisms affects host plant and herbivore responses to warming. Using open-top warming chambers at Harvard Forest, Massachusetts, USA, we manipulated temperature and presence of ants and Chaitophorus populicola aphids on Populus tremuloides host plants and monitored ant attendance and persistence of C. populicola, predator abundance, plant stress, and abundance of Myzus persicae, a pest aphid that colonized plants during the experiment. We found that, regardless of warming, C. populicola persistence was higher when tended by ants, and some ant species increased aphid persistence more than others. Warming had negligible direct but strong indirect effects on plant stress. Plant stress decreased with warming only when both ants and C. populicola aphids were present and engaged in mutualism. Plant stress was increased by warming-induced reductions in predator abundance and increases in M. persicae aphid abundance. Altogether, these findings suggest that insect mutualisms could buffer the effects of warming on specialist herbivores and plants, but when mutualisms are not intact, the direct effects of warming on predators and generalist herbivores yield strong indirect effects of warming on plants.


Assuntos
Formigas/fisiologia , Afídeos/fisiologia , Ecossistema , Populus/fisiologia , Simbiose/fisiologia , Animais , Besouros/fisiologia , Temperatura Alta , Comportamento Predatório , Aranhas/fisiologia
5.
Curr Biol ; 32(24): 5406-5414.e5, 2022 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-36450284

RESUMO

The Drosophila brain contains about 50 distinct morphological types of dopamine neurons.1,2,3,4 Physiological studies of Drosophila dopamine neurons have been largely limited to one brain region, the mushroom body,5,6,7,8,9,10,11,12,13 where they are implicated in learning.14,15,16,17,18 By comparison, we know little about the physiology of other Drosophila dopamine neurons. Interestingly, a recent whole-brain imaging study found that dopamine neuron activity in several fly brain regions is correlated with locomotion.19 This is notable because many dopamine neurons in the rodent brain are also correlated with locomotion or other movements20,21,22,23,24,25,26,27,28,29,30; however, most rodent studies have focused on learned and rewarded behaviors, and few have investigated dopamine neuron activity during spontaneous (self-timed) movements. In this study, we monitored dopamine neurons in the Drosophila brain during self-timed locomotor movements, focusing on several previously uncharacterized cell types that arborize in the superior-lateral brain, specifically the lateral horn and superior-lateral protocerebrum. We found that activity of all of these dopamine neurons correlated with spontaneous fluctuations in walking speed, with different cell types showing different speed correlations. Some dopamine neurons also responded to odors, but these responses were suppressed by repeated odor encounters. Finally, we found that the same identifiable dopamine neuron can encode different combinations of locomotion and odor in different individuals. If these dopamine neurons promote synaptic plasticity-like the dopamine neurons of the mushroom body-then, their tuning profiles would imply that plasticity depends on a flexible integration of sensory signals, motor signals, and recent experience.


Assuntos
Neurônios Dopaminérgicos , Drosophila , Animais , Drosophila/fisiologia , Olfato/fisiologia , Aprendizagem/fisiologia , Encéfalo , Corpos Pedunculados/fisiologia , Drosophila melanogaster/fisiologia
6.
Front Syst Neurosci ; 11: 13, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28377700

RESUMO

How we perceive the world as stable despite the frequent disruptions of the retinal image caused by eye movements is one of the fundamental questions in sensory neuroscience. Seemingly convergent evidence points towards a mechanism which dynamically updates representations of visual space in anticipation of a movement (Wurtz, 2008). In particular, receptive fields (RFs) of neurons, predominantly within oculomotor and attention related brain structures (Duhamel et al., 1992; Walker et al., 1995; Umeno and Goldberg, 1997), are thought to "remap" to their future, post-movement location prior to an impending eye movement. New studies (Neupane et al., 2016a,b) report observations on RF dynamics at the time of eye movements of neurons in area V4. These dynamics are interpreted as being largely dominated by a remapping of RFs. Critically, these observations appear at odds with a previous study reporting a different type of RF dynamics within the same brain structure (Tolias et al., 2001), consisting of a shrinkage and shift of RFs towards the movement target. Importantly, RFs have been measured with different techniques in those studies. Here, we measured V4 RFs comparable to Neupane et al. (2016a,b) and observe a shrinkage and shift of RFs towards the movement target when analyzing the immediate stimulus response (Zirnsak et al., 2014). When analyzing the late stimulus response (Neupane et al., 2016a,b), we observe RF shifts resembling remapping. We discuss possible causes for these shifts and point out important issues which future studies on RF dynamics need to address.

7.
PLoS One ; 12(12): e0188972, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29194435

RESUMO

An average mouse in midlife weighs between 25 and 30 g, with about a gram of tissue in the largest adipose depot (gonadal), and the weight of this depot differs between inbred strains. Specifically, C57BL/6ByJ mice have heavier gonadal depots on average than do 129P3/J mice. To understand the genetic contributions to this trait, we mapped several quantitative trait loci (QTLs) for gonadal depot weight in an F2 intercross population. Our goal here was to fine-map one of these QTLs, Adip20 (formerly Adip5), on mouse chromosome 9. To that end, we analyzed the weight of the gonadal adipose depot from newly created congenic strains. Results from the sequential comparison method indicated at least four rather than one QTL; two of the QTLs were less than 0.5 Mb apart, with opposing directions of allelic effect. Different types of evidence (missense and regulatory genetic variation, human adiposity/body mass index orthologues, and differential gene expression) implicated numerous candidate genes from the four QTL regions. These results highlight the value of mouse congenic strains and the value of this sequential method to dissect challenging genetic architecture.


Assuntos
Adiposidade/genética , Locos de Características Quantitativas , Animais , Feminino , Variação Genética , Masculino , Camundongos
8.
PLoS One ; 10(11): e0141494, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26551037

RESUMO

Genetic variation contributes to individual differences in obesity, but defining the exact relationships between naturally occurring genotypes and their effects on fatness remains elusive. As a step toward positional cloning of previously identified body composition quantitative trait loci (QTLs) from F2 crosses of mice from the C57BL/6ByJ and 129P3/J inbred strains, we sought to recapture them on a homogenous genetic background of consomic (chromosome substitution) strains. Male and female mice from reciprocal consomic strains originating from the C57BL/6ByJ and 129P3/J strains were bred and measured for body weight, length, and adiposity. Chromosomes 2, 7, and 9 were selected for substitution because previous F2 intercross studies revealed body composition QTLs on these chromosomes. We considered a QTL confirmed if one or both sexes of one or both reciprocal consomic strains differed significantly from the host strain in the expected direction after correction for multiple testing. Using these criteria, we confirmed two of two QTLs for body weight (Bwq5-6), three of three QTLs for body length (Bdln3-5), and three of three QTLs for adiposity (Adip20, Adip26 and Adip27). Overall, this study shows that despite the biological complexity of body size and composition, most QTLs for these traits are preserved when transferred to consomic strains; in addition, studying reciprocal consomic strains of both sexes is useful in assessing the robustness of a particular QTL.


Assuntos
Adiposidade/genética , Composição Corporal/genética , Estatura/genética , Tamanho Corporal/genética , Peso Corporal/genética , Locos de Características Quantitativas/genética , Animais , Mapeamento Cromossômico , Cromossomos de Mamíferos , Feminino , Variação Genética/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , Fenótipo
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