Abstract：
:Understanding the origins and evolution of synapses may provide insight into species diversity and the organization of the brain. Using comparative proteomics and genomics, we examined the evolution of the postsynaptic density (PSD) and membrane-associated guanylate kinase (MAGUK)-associated signaling complexes (MASCs) that underlie learning and memory. PSD and MASC orthologs found in yeast carry out basic cellular functions to regulate protein synthesis and structural plasticity. We observed marked changes in signaling complexity at the yeast-metazoan and invertebrate-vertebrate boundaries, with an expansion of key synaptic components, notably receptors, adhesion/cytoskeletal proteins and scaffold proteins. A proteomic comparison of Drosophila and mouse MASCs revealed species-specific adaptation with greater signaling complexity in mouse. Although synaptic components were conserved amongst diverse vertebrate species, mapping mRNA and protein expression in the mouse brain showed that vertebrate-specific components preferentially contributed to differences between brain regions. We propose that the evolution of synapse complexity around a core proto-synapse has contributed to invertebrate-vertebrate differences and to brain specialization.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Emes RD,Pocklington AJ,Anderson CN,Bayes A,Collins MO,Vickers CA,Croning MD,Malik BR,Choudhary JS,Armstrong JD,Grant SGdoi
10.1038/nn.2135subject
Has Abstractpub_date
2008-07-01 00:00:00pages
799-806issue
7eissn
1097-6256issn
1546-1726pii
nn.2135journal_volume
11pub_type
杂志文章abstract：:Medical imaging has enormous potential for early disease prediction, but is impeded by the difficulty and expense of acquiring data sets before symptom onset. UK Biobank aims to address this problem directly by acquiring high-quality, consistently acquired imaging data from 100,000 predominantly healthy participants, ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4393
更新日期：2016-11-01 00:00:00
abstract：:Over the past two centuries, prevalent models of energy and glucose homeostasis have emerged from careful anatomical descriptions in tandem with an understanding of cellular physiology. More recent technological advances have culminated in the identification of peripheral and central factors that influence neural circ...
journal_title：Nature neuroscience
pub_type： 杂志文章,评审
doi：10.1038/nn.3217
更新日期：2012-10-01 00:00:00
abstract：:A hallmark of addiction is the loss of control over drug intake, which is seen in only a fraction of those exposed to stimulant drugs such as cocaine. The cellular mechanisms underlying vulnerability or resistance to compulsive drug use remain unknown. We found that individual variability in the development of highly ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3369
更新日期：2013-05-01 00:00:00
abstract：:The contribution of basal ganglia outputs to consummatory behavior remains poorly understood. We recorded from the substantia nigra pars reticulata (SNR), the major basal ganglia output nucleus, during self-initiated drinking in mice. The firing rates of many lateral SNR neurons were time-locked to individual licks. T...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4285
更新日期：2016-05-01 00:00:00
abstract：:Humans exhibit a remarkable degree of resilience in the face of extreme stress, with most resisting the development of neuropsychiatric disorders. Over the past 5 years, there has been increasing interest in the active, adaptive coping mechanisms of resilience; however, in humans, most published work focuses on correl...
journal_title：Nature neuroscience
pub_type： 杂志文章,评审
doi：10.1038/nn.3234
更新日期：2012-11-01 00:00:00
abstract：:Brain circuitry processes information by rapidly and selectively engaging functional neuronal networks. The dynamic formation of networks is often evident in rhythmically synchronized neuronal activity and tightly correlates with perceptual, cognitive and motor performances. But how synchronized neuronal activity cont...
journal_title：Nature neuroscience
pub_type： 杂志文章,评审
doi：10.1038/nn.3764
更新日期：2014-08-01 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：:It is widely accepted that D1 dopamine receptor-expressing striatal neurons convey their information directly to the output nuclei of the basal ganglia, whereas D2-expressing neurons do so indirectly via pallidal neurons. Combining optogenetics and electrophysiology, we found that this architecture does not apply to m...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4068
更新日期：2015-09-01 00:00:00
abstract：:Age-related decreases in neural function result in part from alterations in synapses. To identify molecular defects that lead to such changes, we focused on the outer retina, in which synapses are markedly altered in old rodents and humans. We found that the serine/threonine kinase LKB1 and one of its substrates, AMPK...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3772
更新日期：2014-09-01 00:00:00
abstract：:Human neurodegenerative disorders are among the most difficult to study. In particular, the inability to readily obtain the faulty cell types most relevant to these diseases has impeded progress for decades. Recent advances in pluripotent stem cell technology now grant access to substantial quantities of disease-perti...
journal_title：Nature neuroscience
pub_type： 杂志文章,评审
doi：10.1038/nn.3425
更新日期：2013-07-01 00:00:00
abstract：:Cocaine is a widely abused substance with psychostimulant effects that are attributed to inhibition of the dopamine transporter (DAT). We present molecular models for DAT binding of cocaine and cocaine analogs constructed from the high-resolution structure of the bacterial transporter homolog LeuT. Our models suggest ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2146
更新日期：2008-07-01 00:00:00
abstract：:EphB receptor tyrosine kinases control multiple steps in nervous system development. However, it remains unclear whether EphBs regulate these different developmental processes directly or indirectly. In addition, given that EphBs signal through multiple mechanisms, it has been challenging to define which signaling fun...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3249
更新日期：2012-12-01 00:00:00
abstract：:Dopaminergic (DA) signaling governs the control of complex behaviors, and its deregulation has been implicated in a wide range of diseases. Here we demonstrate that inactivation of the Fto gene, encoding a nucleic acid demethylase, impairs dopamine receptor type 2 (D2R) and type 3 (D3R) (collectively, 'D2-like recepto...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3449
更新日期：2013-08-01 00:00:00
abstract：:Olfactory representations are shaped by brain state and respiration. The interaction and circuit substrates of these influences are unclear. Granule cells (GCs) in the main olfactory bulb (MOB) are presumed to sculpt activity reaching the cortex via inhibition of mitral/tufted cells (MTs). GCs potentially make ensembl...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3669
更新日期：2014-04-01 00:00:00
abstract：:A fundamental organizing principle of auditory brain circuits is tonotopy, the orderly representation of the sound frequency to which neurons are most sensitive. Tonotopy arises from the coding of frequency along the cochlea and the topographic organization of auditory pathways. The mechanisms that underlie the establ...
journal_title：Nature neuroscience
pub_type： 杂志文章,评审
doi：10.1038/nn.2332
更新日期：2009-06-01 00:00:00
abstract：:Short-term synaptic plasticity is a defining feature of neuronal activity, but the underlying molecular mechanisms are poorly understood. Depression of synaptic activity might be due to limited vesicle availability, whereas facilitation is thought to result from elevated calcium levels. However, it is unclear whether ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1117
更新日期：2003-10-01 00:00:00
abstract：:The most critical attribute of human language is its unbounded combinatorial nature: smaller elements can be combined into larger structures on the basis of a grammatical system, resulting in a hierarchy of linguistic units, such as words, phrases and sentences. Mentally parsing and representing such structures, howev...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4186
更新日期：2016-01-01 00:00:00
abstract：:Fever is a result of the action of prostaglandin E2 (PGE2) on the brain and appears to require EP3 prostaglandin receptors (EP3Rs), but the specific neurons on which PGE2 acts to produce fever have not been definitively established. Here we report that selective genetic deletion of the EP3Rs in the median preoptic nuc...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1949
更新日期：2007-09-01 00:00:00
abstract：:EphAs and ephrinAs are expressed in multiple areas of the developing brain in overlapping countergradients, notably in the retina and tectum. Here they are involved in targeting retinal axons to their correct topographic position in the tectum. We have used truncated versions of EphA3, single-amino acid point mutants ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1655
更新日期：2006-03-01 00:00:00
abstract：:Sensory pathways are typically studied by starting at receptor neurons and following postsynaptic neurons into the brain. However, this leads to a bias in analyses of activity toward the earliest layers of processing. Here, we present new methods for volumetric neural imaging with precise across-brain registration to ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-020-00743-y
更新日期：2021-01-01 00:00:00
abstract：:In the nose, odorants are detected on the cilia of olfactory sensory neurons (OSNs), where a cAMP-mediated signaling pathway transforms odor stimulation into electrical responses. Phosphodiesterase (PDE) activity in OSN cilia has long been thought to account for rapid response termination by degrading odor-induced cAM...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2289
更新日期：2009-04-01 00:00:00
abstract：:The precise role of synchronous neuronal firing in signal encoding remains unclear. To examine what kinds of signals can be carried by synchrony, I reproduced a multilayer feedforward network of neurons in an in vitro slice preparation of rat cortex using an iterative procedure. When constant and time-varying frequenc...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1056
更新日期：2003-06-01 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：:Sustained activity encoding visual working memory representations has been observed in several cortical areas of primates. Where along the visual pathways this activity emerges remains unknown. Here we show in macaques that sustained spiking activity encoding memorized visual motion directions is absent in direction-s...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3785
更新日期：2014-09-01 00:00:00
abstract：:Every year in the United States, an estimated 500,000 babies are born preterm (before 37 completed weeks of gestation), and this number is rising, along with the recognition of brain injuries due to preterm delivery. A common underlying pathogenesis appears to be perinatal hypoxia induced by immature lung development,...
journal_title：Nature neuroscience
pub_type： 杂志文章,评审
doi：10.1038/nn.3604
更新日期：2014-03-01 00:00:00
abstract：:Fear-inducing memories can be state dependent, meaning that they can best be retrieved if the brain states at encoding and retrieval are similar. Restricted access to such memories can present a risk for psychiatric disorders and hamper their treatment. To better understand the mechanisms underlying state-dependent fe...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4084
更新日期：2015-09-01 00:00:00
abstract：:The healthy human brain is a mosaic of varied genomes. Long interspersed element-1 (LINE-1 or L1) retrotransposition is known to create mosaicism by inserting L1 sequences into new locations of somatic cell genomes. Using a machine learning-based, single-cell sequencing approach, we discovered that somatic L1-associat...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4388
更新日期：2016-12-01 00:00:00
abstract：:T cells clear virus from the CNS and dynamically regulate brain functions, including spatial learning, through cytokine signaling. Here we determined whether hippocampal T cells that persist after recovery from infection with West Nile virus (WNV) or Zika virus (ZIKV) impact hippocampal-dependent learning and memory. ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-019-0427-y
更新日期：2019-08-01 00:00:00
abstract：:Neurons in thalamorecipient layers of sensory cortices integrate thalamocortical and intracortical inputs. Although we know that their functional properties can arise from the convergence of thalamic inputs, intracortical circuits could also be involved in thalamocortical transformations of sensory information. We sil...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3494
更新日期：2013-09-01 00:00:00
abstract：:Protein-coding de novo mutations (DNMs) are significant risk factors in many neurodevelopmental disorders, whereas schizophrenia (SCZ) risk associated with DNMs has thus far been shown to be modest. We analyzed DNMs from 1,695 SCZ-affected trios and 1,077 published SCZ-affected trios to better understand the contribut...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-019-0564-3
更新日期：2020-02-01 00:00:00
