Abstract:
:The mechanistic target of rapamycin (mTOR) acts as a highly conserved signaling "hub" that integrates neuronal activity and a variety of synaptic inputs. mTOR is found in two functionally distinct complexes, mTORC1 and mTORC2, that crucially control long-term synaptic efficacy and memory storage. Dysregulation of mTOR signaling is associated with neurodevelopmental and neuropsychiatric disorders. In this Review, we describe the most recent advances in studies of mTOR signaling in the brain and the possible mechanisms underlying the many different functions of the mTOR complexes in neurological diseases. In addition, we discuss the medical relevance of these findings.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Costa-Mattioli M,Monteggia LMdoi
10.1038/nn.3546subject
Has Abstractpub_date
2013-11-01 00:00:00pages
1537-43issue
11eissn
1097-6256issn
1546-1726pii
nn.3546journal_volume
16pub_type
杂志文章,评审abstract::Here we report that synaptic and extrasynaptic NMDA (N-methyl-D-aspartate) receptors have opposite effects on CREB (cAMP response element binding protein) function, gene regulation and neuron survival. Calcium entry through synaptic NMDA receptors induced CREB activity and brain-derived neurotrophic factor (BDNF) gene...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn835
更新日期:2002-05-01 00:00:00
abstract::Phosphoinositide 3 kinase enhancer (PIKE) is a recently identified nuclear GTPase that activates nuclear phosphoinositide 3-kinase (PI3 kinase). We have identified, cloned and characterized a new form of PIKE, designated PIKE-L, which, unlike the nuclear PIKE-S, localizes to both the cytoplasm and the nucleus. We demo...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn1134
更新日期:2003-11-01 00:00:00
abstract::Speech and vocal impairments characterize many neurological disorders. However, the neurogenetic mechanisms of these disorders are not well understood, and current animal models do not have the necessary circuitry to recapitulate vocal learning deficits. We developed germline transgenic songbirds, zebra finches (Tanei...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.4133
更新日期:2015-11-01 00:00:00
abstract::Neuronal differentiation is accomplished through cascades of intrinsic genetic factors initiated in neuronal progenitors by external gradients of morphogens. Activity has been thought to be important only late in development, but recent evidence suggests that activity also regulates early neuronal differentiation. Act...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.2582
更新日期:2010-08-01 00:00:00
abstract::We report a systematic relationship between sound-frequency tuning and sensitivity to interaural time delays for neurons in the midbrain nucleus of the inferior colliculus; neurons with relatively low best frequencies (BFs) showed response peaks at long delays, whereas neurons with relatively high BFs showed response ...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/86049
更新日期:2001-04-01 00:00:00
abstract::Transcriptomic analyses of postmortem brains have begun to elucidate molecular abnormalities in autism spectrum disorder (ASD). However, a crucial pathway involved in synaptic development, RNA editing, has not yet been studied on a genome-wide scale. Here we profiled global patterns of adenosine-to-inosine (A-to-I) ed...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/s41593-018-0287-x
更新日期:2019-01-01 00:00:00
abstract::Many cells in retinotopic brain areas increase their activity when saccades (rapid eye movements) are about to bring stimuli into their receptive fields. Although previous work has attempted to look at the functional correlates of such predictive remapping, no study has explicitly tested for better attentional perform...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.2711
更新日期:2011-02-01 00:00:00
abstract::We show that a natural behavior, exploration of a novel environment, causes DNA double-strand breaks (DSBs) in neurons of young adult wild-type mice. DSBs occurred in multiple brain regions, were most abundant in the dentate gyrus, which is involved in learning and memory, and were repaired within 24 h. Increasing neu...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.3356
更新日期:2013-05-01 00:00:00
abstract::To discover novel genes underlying amyotrophic lateral sclerosis (ALS), we aggregated exomes from 3,864 cases and 7,839 ancestry-matched controls. We observed a significant excess of rare protein-truncating variants among ALS cases, and these variants were concentrated in constrained genes. Through gene level analyses...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/s41593-019-0530-0
更新日期:2019-12-01 00:00:00
abstract::The identity of specific cell types in the nervous system is defined by the expression of neuron type-specific gene batteries. How the expression of such batteries is initiated during nervous system development has been under intensive study over the past few decades. However, comparatively little is known about how g...
journal_title:Nature neuroscience
pub_type: 杂志文章,评审
doi:10.1038/nn.3731
更新日期:2014-07-01 00:00:00
abstract::Previous gene knockout studies have shown that the orphan glutamate receptor delta2 (GluRdelta2) is critically involved in synaptogenesis between parallel fibers and Purkinje cells during development. However, the precise function of GluRdelta2 and whether it is functional in the mature cerebellum remain unclear. To a...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn1086
更新日期:2003-08-01 00:00:00
abstract::Intrinsic signal imaging from inferotemporal (IT) cortex, a visual area essential for object perception and recognition, revealed that visually presented objects activated patches in a distributed manner. When visual features of these objects were partially removed, the simplified stimuli activated only a subset of th...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/90547
更新日期:2001-08-01 00:00:00
abstract::Axon degeneration is a hallmark of many neurodegenerative disorders. The current assumption is that the decision of injured axons to degenerate is cell-autonomously regulated. Here we show that Schwann cells (SCs), the glia of the peripheral nervous system, protect injured axons by virtue of a dramatic glycolytic upre...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/s41593-020-0689-4
更新日期:2020-10-01 00:00:00
abstract::Human chromosome 16p11.2 microdeletion is the most common gene copy number variation in autism, but the synaptic pathophysiology caused by this mutation is largely unknown. Using a mouse with the same genetic deficiency, we found that metabotropic glutamate receptor 5 (mGluR5)-dependent synaptic plasticity and protein...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.3911
更新日期:2015-02-01 00:00:00
abstract::Learning to adapt to a complex and fluctuating environment requires the ability to adjust neural representations of sensory stimuli. Through pattern completion processes, cortical networks can reconstruct familiar patterns from degraded input patterns, whereas pattern separation processes allow discrimination of even ...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.2966
更新日期:2011-11-20 00:00:00
abstract::Studies of populations of receptor proteins suggest that their number and location are highly regulated. Single-particle tracking of glycine receptors now reveals the direct movement of receptors between different clusters of the anchoring protein gephyrin. ...
journal_title:Nature neuroscience
pub_type: 评论,杂志文章,评审
doi:10.1038/85042
更新日期:2001-03-01 00:00:00
abstract::Cognition can be conceptualized as a set of algorithmic control functions whose real-time deployment determines how an organism stores and uses information to guide thought and action. A subset of these functions is required for goal-directed selection and amplification of sensory signals-broadly referred to as attent...
journal_title:Nature neuroscience
pub_type: 杂志文章,评审
doi:10.1038/s41593-017-0020-1
更新日期:2017-12-01 00:00:00
abstract::Adult neurogenesis occurs in the hippocampus and the olfactory bulb of the mammalian CNS. Recent studies have demonstrated that newborn granule cells of the adult hippocampus are postsynaptic targets of excitatory and inhibitory neurons, but evidence of synapse formation by the axons of these cells is still lacking. B...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.2156
更新日期:2008-08-01 00:00:00
abstract::Persistent neural activity in the absence of a stimulus has been identified as a neural correlate of working memory, but how such activity is maintained by neocortical circuits remains unknown. We used a computational approach to show that the inhibitory and excitatory microcircuitry of neocortical memory-storing regi...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.3492
更新日期:2013-09-01 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::It is often assumed that all neurons of the same cell type have identical intrinsic properties, both within an animal and between animals. We exploited the large size and small number of unambiguously identifiable neurons in the crab stomatogastric ganglion to test this assumption at the level of channel mRNA expressi...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn1639
更新日期:2006-03-01 00:00:00
abstract::Many attempts to obtain reliable self-administration behavior by laboratory animals with delta-9-tetrahydrocannabinol (THC), the psychoactive ingredient in marijuana, have been unsuccessful. Because self-administration behavior has been demonstrated in laboratory animals for almost all other psychoactive drugs abused ...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/80577
更新日期:2000-11-01 00:00:00
abstract::Understanding a sensory system implies the ability to predict responses to a variety of inputs from a common model. In the retina, this includes predicting how the integration of signals across visual space shapes the outputs of retinal ganglion cells. Existing models of this process generalize poorly to predict respo...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.3225
更新日期:2012-11-01 00:00:00
abstract::We report two functional magnetic resonance imaging experiments showing enhanced responses in human middle superior temporal sulcus for angry relative to neutral prosody. This emotional enhancement was voice specific, unrelated to isolated acoustic amplitude or frequency cues in angry prosody, and distinct from any co...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn1392
更新日期:2005-02-01 00:00:00
abstract::Neurons in the rat primary auditory cortex (A1) generally cannot respond to tone sequences faster than 12 pulses per second (pps). To test whether experience can modify this maximum following rate in adult rats, trains of brief tones with random carrier frequency but fixed repetition rate were paired with electrical s...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/3729
更新日期:1998-12-01 00:00:00
abstract::Repeated cocaine administration increases the dendritic arborization of nucleus accumbens neurons, but the underlying signaling events remain unknown. Here we show that repeated exposure to cocaine negatively regulates the active form of Rac1, a small GTPase that controls actin remodeling in other systems. Further, we...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn.3094
更新日期:2012-06-01 00:00:00
abstract::Ample evidence suggests that primary visual cortex is involved in the perception of form, and there is increasing evidence that it may also be important in the perception of surfaces. Perceptual qualities of surfaces, such as brightness, are based on extensive integration of information throughout the visual field. In...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/2849
更新日期:1998-11-01 00:00:00
abstract::We investigated the regulation of T-type channels by Rho-associated kinase (ROCK). Activation of ROCK via the endogenous ligand lysophosphatidic acid (LPA) reversibly inhibited the peak current amplitudes of rat Ca(v)3.1 and Ca(v)3.3 channels without affecting the voltage dependence of activation or inactivation, wher...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn1921
更新日期:2007-07-01 00:00:00
abstract::Synaptic stimulation activates signal transduction pathways, producing persistently active protein kinases. PKMzeta is a truncated, persistently active isoform of atypical protein kinase C-zeta (aPKCzeta), which lacks the N-terminal pseudosubstrate regulatory domain. Using a Pavlovian olfactory learning task in Drosop...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn820
更新日期:2002-04-01 00:00:00
abstract::Experience-dependent plasticity in adult visual cortex is believed to have important roles in visual coding and perceptual learning. Here we show that repeated stimulation with movies of natural scenes induces a rapid improvement in response reliability in cat visual cortex, whereas stimulation with white noise or fla...
journal_title:Nature neuroscience
pub_type: 杂志文章
doi:10.1038/nn1895
更新日期:2007-06-01 00:00:00