Abstract:
:The melanocortin system provides a conceptual blueprint for the central control of energetic state. Defined by four principal molecular components--two antagonistically acting ligands and two cognate receptors--this phylogenetically conserved system serves as a prototype for hierarchical energy balance regulation. Over the last decade the application of conditional genetic techniques has facilitated the neuroanatomical dissection of the melanocortinergic network and identified the specific neural substrates and circuits that underscore the regulation of feeding behavior, energy expenditure, glucose homeostasis and autonomic outflow. In this regard, the melanocortin-4 receptor is a critical coordinator of mammalian energy homeostasis and body weight. Drawing on recent advances in neuroscience and genetic technologies, we consider the structure and function of the melanocortin-4 receptor circuitry and its role in energy homeostasis.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Krashes MJ,Lowell BB,Garfield ASdoi
10.1038/nn.4202subject
Has Abstractpub_date
2016-02-01 00:00:00pages
206-19issue
2eissn
1097-6256issn
1546-1726pii
nn.4202journal_volume
19pub_type
杂志文章,评审abstract::Dopamine is vital for coordinated motion and for association learning linked to behavioral reinforcement. Here we show that the precise overlap of striatal dopaminergic and cholinergic fibers underlies potent control of dopamine release by ongoing nicotinic receptor activity. In mouse striatal slices, nicotinic antago...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn769
更新日期:2001-12-01 00:00:00
abstract::A hallmark event in neurodegenerative diseases (NDs) is the misfolding, aggregation, and accumulation of proteins, leading to cellular dysfunction, loss of synaptic connections, and brain damage. Despite the involvement of distinct proteins in different NDs, the process of protein misfolding and aggregation is remarka...
journal_title:Nature neuroscience
pub_type: 杂志文章,评审
doi:10.1038/s41593-018-0235-9
更新日期:2018-10-01 00:00:00
abstract::The molecular trigger of CNS myelination is unknown. By targeting Pten in cerebellar granule cells and activating the AKT1-mTOR pathway, we increased the caliber of normally unmyelinated axons and the expression of numerous genes encoding regulatory proteins. This led to the expansion of genetically wild-type oligoden...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.4425
更新日期:2017-01-01 00:00:00
abstract::Exposure to a stressor sensitizes behavioral and hormonal responses to future stressors. Stress-associated release of noradrenaline enhances the capacity of central synapses to show plasticity (metaplasticity). We found noradrenaline-dependent metaplasticity at GABA synapses in the paraventricular nucleus of the hypot...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.3373
更新日期:2013-05-01 00:00:00
abstract::In this report we describe how common brain networks within the medial frontal cortex (MFC) facilitate adaptive behavioral control in rodents and humans. We demonstrate that after errors, low-frequency oscillations below 12 Hz are modulated over the midfrontal cortex in humans and within the prelimbic and anterior cin...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.3549
更新日期:2013-12-01 00:00:00
abstract::A localized transcriptome at the synapse facilitates synapse-, stimulus- and transcript-specific local protein synthesis in response to neuronal activity. While enzyme-mediated mRNA modifications are known to regulate cellular mRNA turnover, the role of these modifications in regulating synaptic RNA has not been studi...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/s41593-018-0173-6
更新日期:2018-07-01 00:00:00
abstract::Olfaction has often been described as a ‘synthetic’ sense. A study now reveals a surprising capacity to resolve individual odorants in complex mixtures, with implications for how the nervous system recognizes objects. ...
journal_title:Nature neuroscience
pub_type: 评论,杂志文章
doi:10.1038/nn.3796
更新日期:2014-09-01 00:00:00
abstract::Neurons in many species have large receptive fields that are selective for specific optic flow fields. Here, we studied the neural mechanisms underlying flow field selectivity in lobula plate tangential cells (LPTCs) of the blowfly. Among these cells, the H2 cell responds preferentially to visual stimuli approximating...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn1769
更新日期:2006-10-01 00:00:00
abstract::An ion channel's function depends largely on its location and density on neurons. Here we used high-resolution immunolocalization to determine the subcellular distribution of the hyperpolarization-activated and cyclic-nucleotide-gated channel subunit 1 (HCN1) in rat brain. Light microscopy revealed graded HCN1 immunor...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn962
更新日期:2002-11-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature neuroscience
pub_type: 已发布勘误
doi:10.1038/s41593-019-0570-5
更新日期:2020-02-01 00:00:00
abstract::The deposition of aggregated amyloid-β peptides derived from the pro-amyloidogenic processing of the amyloid precurson protein (APP) into characteristic amyloid plaques (APs) is distinctive to Alzheimer's disease (AD). Alternative APP processing via the metalloprotease ADAM10 prevents amyloid-β formation. We tested wh...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/s41593-019-0432-1
更新日期:2019-08-01 00:00:00
abstract::Communication between glia cells and neurons is crucial for brain functions, but the molecular mechanisms and functional consequences of gliotransmission remain enigmatic. Here we report that astrocytes express synaptobrevin II and cellubrevin as functionally non-overlapping vesicular SNARE proteins on glutamatergic v...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.4647
更新日期:2017-11-01 00:00:00
abstract::Neocortical GABAergic neurons have diverse molecular, structural and electrophysiological features, but the functional correlates of this diversity are largely unknown. We found unique membrane potential dynamics of somatostatin-expressing (SOM) neurons in layer 2/3 of the primary somatosensory barrel cortex of awake ...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.3051
更新日期:2012-02-26 00:00:00
abstract::We examined enhancement of synaptic transmission by neurotrophins at the presynaptic level. In a synaptosomal preparation, brain-derived neurotrophic factor (BDNF) increased mitogen-activated protein (MAP) kinase-dependent synapsin I phosphorylation and acutely facilitated evoked glutamate release. PD98059, used to in...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/73888
更新日期:2000-04-01 00:00:00
abstract::Multiple protein kinase C (PKC) isozymes are present in neurons, where they regulate a variety of cellular functions. Due to the lack of specific PKC isozyme inhibitors, it remains unknown how PKC acts on its selective target(s) and achieves its specific actions. Here we show that a PKC binding protein, enigma homolog...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn1041
更新日期:2003-05-01 00:00:00
abstract::Autism spectrum disorder (ASD) is genetically heterogeneous with convergent symptomatology, suggesting common dysregulated pathways. In this study, we analyzed brain transcriptional changes in five mouse models of Pitt-Hopkins syndrome (PTHS), a syndromic form of ASD caused by mutations in the TCF4 gene, but not the T...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/s41593-019-0578-x
更新日期:2020-03-01 00:00:00
abstract::The molecular organization of presynaptic active zones is important for the neurotransmitter release that is triggered by depolarization-induced Ca2+ influx. Here, we demonstrate a previously unknown interaction between two components of the presynaptic active zone, RIM1 and voltage-dependent Ca2+ channels (VDCCs), th...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn1904
更新日期:2007-06-01 00:00:00
abstract::Neuroimaging studies show that the efficacy of long-term memory encoding of a stimulus is indexed by transient neural activity elicited by that stimulus. Here, we show that successful memory encoding is also indexed by neural activity that is tonically maintained throughout a study task. Using functional magnetic reso...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn967
更新日期:2002-12-01 00:00:00
abstract::Behavior-contingent network oscillations bring about transient, functionally coherent neuronal assemblies in the cerebral cortex, including the hippocampus. Inhibitory input on and close to the soma is believed to phase intrinsic oscillations and output of pyramidal cells, but the function of GABA release to pyramidal...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn1159
更新日期:2004-01-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature neuroscience
pub_type: 已发布勘误
doi:10.1038/s41593-020-00710-7
更新日期:2020-11-01 00:00:00
abstract::Phasic activation of the dopamine (DA) midbrain system in response to unexpected reward or novelty is critical for adaptive behavioral strategies. This activation of DA midbrain neurons occurs via a synaptically triggered switch from low-frequency background spiking to transient high-frequency burst firing. We found t...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.3185
更新日期:2012-09-01 00:00:00
abstract::Cue-triggered recall of learned temporal sequences is an important cognitive function that has been attributed to higher brain areas. Here recordings in both anesthetized and awake rats demonstrate that after repeated stimulation with a moving spot that evoked sequential firing of an ensemble of primary visual cortex ...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.3036
更新日期:2012-01-22 00:00:00
abstract::The shift in ocular dominance induced by brief monocular deprivation is greatest during a postnatal critical period and is thought to decline irreversibly thereafter. However, here we demonstrate that complete visual deprivation through dark exposure restores rapid ocular dominance plasticity in adult rats. In additio...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn1965
更新日期:2007-09-01 00:00:00
abstract::Anatomical studies have led to the assertion that intratelencephalic and pyramidal tract cortical neurons innervate different striatal projection neurons. To test this hypothesis, we measured the responses of mouse striatal neurons to optogenetic activation of intratelencephalic and pyramidal tract axons. Contrary to ...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.3397
更新日期:2013-06-01 00:00:00
abstract::Although the prefrontal cortex influences motivated behavior, its role in food intake remains unclear. Here, we demonstrate a role for D1-type dopamine receptor-expressing neurons in the medial prefrontal cortex (mPFC) in the regulation of feeding. Food intake increases activity in D1 neurons of the mPFC in mice, and ...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.3625
更新日期:2014-02-01 00:00:00
abstract::An unresolved question in neuroscience relates to the extent to which corticothalamocortical circuits emanating from layer 5B are involved in information transfer through the cortical hierarchy. Using a new form of optical imaging in a brain slice preparation, we found that the corticothalamocortical pathway drove rob...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.2449
更新日期:2010-01-01 00:00:00
abstract::The 'cognitive map' hypothesis proposes that brain builds a unified representation of the spatial environment to support memory and guide future action. Forty years of electrophysiological research in rodents suggest that cognitive maps are neurally instantiated by place, grid, border and head direction cells in the h...
journal_title:Nature neuroscience
pub_type: 杂志文章,评审
doi:10.1038/nn.4656
更新日期:2017-10-26 00:00:00
abstract::The distinct electrical properties of axonal and dendritic membranes are largely a result of specific transport of vesicle-bound membrane proteins to each compartment. How this specificity arises is unclear because kinesin motors that transport vesicles cannot autonomously distinguish dendritically projecting microtub...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.2318
更新日期:2009-05-01 00:00:00
abstract::The identification of distinct cell types in the basal ganglia has been critical to our understanding of basal ganglia function and the treatment of neurological disorders. The external globus pallidus (GPe) is a key contributor to motor suppressing pathways in the basal ganglia, yet its neuronal heterogeneity has rem...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.4559
更新日期:2017-06-01 00:00:00
abstract::We report on two brain-damaged subjects who exhibit the uncommon pattern of loss of object color knowledge, but spared color perception and naming. The subject P.C.O., as in previously reported patients, is also impaired in processing other perceptual and functional properties of objects. I.O.C., in contrast, is the f...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/88497
更新日期:2001-06-01 00:00:00