source_doi stringlengths 13 57 | source_mag_paper_id int64 490k 157M | source_abstract stringlengths 8 10.7k | target_doi stringlengths 14 27 | target_summary stringlengths 42 889 |
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10.1523/jneurosci.3816-11.2011 | 38,871,212 | Relapse to cocaine-seeking involves impairments in plasticity at glutamatergic synapses in the nucleus accumbens. Integrins are cell adhesion molecules that bind to the extracellular matrix and regulate aspects of synaptic plasticity, including glutamate receptor trafficking. To determine a role for integrins in cocain... | 10.1038/nrn.2016.138 | This study provides the first evidence for a correlation between temporal changes of β3-containing integrin level in the NAc during cocaine withdrawal and relapse to cocaine-seeking behaviour. |
10.1083/jcb.144.3.507 | 38,574,198 | In mature neurons, synaptic vesicles continuously recycle within the presynaptic nerve terminal. In developing axons which are free of contact with a postsynaptic target, constitutive membrane recycling is not localized to the nerve terminal; instead, plasma membrane components undergo cycles of exoendocytosis througho... | 10.1038/nrn1370 | References 37–41 describe the ability of synaptic vesicles to recycle along the length of developing axons. |
10.1002/syn.890030312 | 81,059,003 | Abstract This article reviews studies of the formation of synaptic junctions in the vertebrate central nervous system. It is focused on electron microscopic investigations of synaptogenesis, although insights from other disciplines are interwoven where appropriate, as part of the review is concerned with the morphologi... | 10.1038/nrn1370 | An excellent review of the morphological changes that occur during nascent synapse formation. It also provides insightful suggestions as to mechanisms of synaptogenesis. |
10.1046/j.1471-4159.1998.71051987.x | 58,434,361 | Abstract: Using an immunocytochemical assay to monitor synaptic vesicle exocytosis/endocytosis independently of neurotransmitter release, we have investigated some aspects of vesicle recycling in hippocampal neurons at different developmental stages. A calcium‐ and depolarization‐dependent exocytotic/endocytotic recycl... | 10.1038/nrn1370 | References 78–81 demonstrate that synaptic vesicle recycling along axons is functionally different to that at synapses. |
10.1126/science.291.5504.657 | 41,622,054 | Although astrocytes constitute nearly half of the cells in our brain, their function is a long-standing neurobiological mystery. Here we show by quantal analyses, FM1-43 imaging, immunostaining, and electron microscopy that few synapses form in the absence of glial cells and that the few synapses that do form are funct... | 10.1038/nrn1370 | This paper demonstrates the crucial role of glia in synaptogenesis. |
10.1126/science.1061395 | 17,602,092 | The temporal pattern and relative timing of action potentials among neocortical neurons may carry important information. However, how cortical circuits detect or generate coherent activity remains unclear. Using paired recordings in rat neocortical slices, we found that the firing of fast-spiking cells can reflect the ... | 10.1038/nrn3708 | The authors propose that electrical synapses operate as coincidence detectors in networks of electrically coupled neurons. |
10.1073/pnas.0805408105 | 122,871,733 | Electrical synapses can undergo activity-dependent plasticity. The calcium/calmodulin-dependent kinase II (CaMKII) appears to play a critical role in this phenomenon, but the underlying mechanisms of how CaMKII affects the neuronal gap junction protein connexin36 (Cx36) are unknown. Here we demonstrate effective bindin... | 10.1038/nrn3708 | The paper provides evidence for the existence of direct protein–protein interactions between gap junction-forming proteins and CaMKII, a regulatory kinase that also regulates chemical synapses. |
10.1523/jneurosci.4336-03.2004 | 81,795,454 | The formation and subsequent elimination of electrical coupling between neurons has been demonstrated in many developing vertebrate and invertebrate nervous systems. The relationship between the disappearance of electrical synaptic connectivity and the appearance of chemical neurotransmission is not well understood. We... | 10.1038/nrn3708 | Using a reduced invertebrate model, the authors unambiguously demonstrate the inter-relationship between the formation of electrical and chemical synapses. |
10.1523/jneurosci.2331-10.2010 | 82,114,144 | Electrical and chemical synapses provide two distinct modes of direct communication between neurons, and the embryonic development of the two is typically not simultaneous. Instead, in both vertebrates and invertebrates, gap junction-based electrical synapses arise before chemical synaptogenesis, and the early circuits... | 10.1038/nrn3708 | This study elegantly demonstrates the initial requirement of electrical synapses for the formation of chemical synapses in an in vivo system. |
10.1113/jphysiol.2002.028159 | 85,668,416 | Neonatal rat motoneurones are electrically coupled via gap junctions and the incidence of this coupling declines during postnatal development. The mechanisms involved in this developmental regulation of gap junctional communication are largely unknown. Here we have studied the role of NMDA receptor‐mediated glutamaterg... | 10.1038/nrn3708 | The paper provides evidence for the existence of an inverse relationship between the presence of electrical synapses and chemical synapses in the mammalian brain. |
10.1073/pnas.0808946106 | 64,277,537 | Spontaneous and patterned activity, largely attributed to chemical transmission, shape the development of virtually all neural circuits. However, electrical transmission also has an important role in coordinated activity in the brain. In the olfactory bulb, gap junctions between apical dendrites of mitral cells increas... | 10.1038/nrn3708 | The paper demonstrates the existence of deficits in the formation of circuits formed by chemical synapses in mice lacking the gap junction protein CX36. |
10.1073/pnas.95.22.13272 | 27,951,922 | While chemical synapses are very plastic and modifiable by defined activity patterns, gap junctions, which mediate electrical transmission, have been classically perceived as passive intercellular channels. Excitatory transmission between auditory afferents and the goldfish Mauthner cell is mediated by coexisting gap j... | 10.1038/nrn3708 | The paper provides the first evidence for the role of CaMKII in regulating electrical transmission. |
10.1523/jneurosci.3872-11.2012 | 61,778,242 | In the mammalian CNS, excessive release of glutamate and overactivation of glutamate receptors are responsible for the secondary (delayed) neuronal death following neuronal injury, including ischemia, traumatic brain injury (TBI), and epilepsy. The coupling of neurons by gap junctions (electrical synapses) increases du... | 10.1038/nrn3708 | The authors describe the relationship between glutamate and increased gap junctional coupling observed after neuronal injury and its underlying mechanisms. |
10.1542/peds.2008-1336 | 122,688,979 | OBJECTIVE. Pediatric influenza-associated death became a nationally notifiable condition in the United States during 2004. We describe influenza-associated pediatric mortality from 2004 to 2007, including an increase of Staphylococcus aureus coinfections. METHODS. Influenza-associated pediatric death is defined as a de... | 10.1038/nrmicro3231 | This large epidemiological study shows an increase in influenza virus– S. aureus co-infections with the emergence of the USA300 genotype in the United States. |
10.3851/imp1730 | 80,066,379 | Bacterial super-infections contribute to the significant morbidity and mortality associated with influenza and other respiratory virus infections. There are robust animal model data, but only limited clinical information on the effectiveness of licensed antiviral agents for the treatment of bacterial complications of i... | 10.1038/nrmicro3231 | This paper reviews the mechanisms and our current knowledge of related treatment modalities for viral–bacterial co-infections. |
10.1084/jem.20070891 | 27,008,211 | The World Health Organization estimates that lower respiratory tract infections (excluding tuberculosis) account for ∼35% of all deaths caused by infectious diseases. In many cases, the cause of death may be caused by multiple pathogens, e.g., the life-threatening bacterial pneumonia observed in patients infected with ... | 10.1038/nrmicro3231 | This paper shows that innate immune defects persist for months after influenza in mice. |
10.1084/jem.54.3.349 | 18,588,673 | Swine influenza has been induced in pigs by the intranasal instillation of material from spontaneous cases of the disease as occurring epizootically in eastern Iowa. The experimental disease has the same features as the epizootic. It has been maintained for study by serial passages accomplished either by intranasal ins... | 10.1038/nrmicro3231 | This is a classic paper showing that the manifestation of disease during viral infection requires a co-infecting pathogen. |
10.1152/jn.00581.2007 | 36,482,614 | Neurons in the superficial dorsal horn (SDH) of the spinal cord play a critical role in processing potentially painful or noxious signals from skin, muscle, and viscera. Many acute pain therapies are based on the notion that altering the excitability of SDH neurons can block or gate these signals and reduce pain. This ... | 10.1038/nrn2947 | A review that highlights the heterogeneity of neurons in the superficial dorsal horn and emphasizes the need to identify functional populations. |
10.1113/jphysiol.2001.012890 | 123,715,370 | Relationships between the morphology of individual neurones of the spinal superficial dorsal horn (SDH), laminae I and II, and their electrophysiological properties were studied in spinal cord slices prepared from anaesthetized, free‐ranging hamsters. Tight‐seal, whole‐cell recordings were made with pipette microelectr... | 10.1038/nrn2947 | This combined physiological and morphological study developed the most widely used classification scheme for superficial dorsal horn neurons. |
10.1523/jneurosci.0102-05.2005 | 81,795,579 | Neural circuitry of the spinal superficial dorsal horn (SDH) (laminae I and II) and its relationship to pain and other somatosensory phenomena remain poorly understood. To gain information on this issue, synaptic connections between identified SDH neurons were studied in rat spinal cord slices by simultaneous whole-cel... | 10.1038/nrn2947 | One of a series of papers describing elegant studies in which paired recordings were used to investigate synaptic linkages in the superficial dorsal horn. In this case, a synaptic connection between glutamatergic vertical cells and NK1R-expressing lamina I projection neurons was revealed. |
10.1126/science.278.5336.275 | 19,064,713 | Substance P is released in the spinal cord in response to painful stimuli, but its role in nociceptive signaling remains unclear. When a conjugate of substance P and the ribosome-inactivating protein saporin was infused into the spinal cord, it was internalized and cytotoxic to lamina I spinal cord neurons that express... | 10.1038/nrn2947 | By selectively ablating NK1R-expressing dorsal horn neurons in vivo , the authors demonstrated that these cells play a pivotal part in the development of hyperalgesia. |
10.1523/jneurosci.22-10-04103.2002 | 19,247,316 | Lamina I of the spinal cord is densely innervated by nociceptive primary afferents, many of which contain substance P. It contains numerous projection neurons: the majority of these respond to noxious stimuli, however some are activated by cooling. In the rat, ∼80% of the projection neurons express the neurokinin 1 (NK... | 10.1038/nrn2947 | This article demonstrated a strong monosynaptic input from substance P-containing (nociceptive) primary afferents to lamina I projection neurons that express the NK1R. |
10.1152/physrev.00025.2008 | 103,740,977 | Hyperalgesia and allodynia are frequent symptoms of disease and may be useful adaptations to protect vulnerable tissues. Both may, however, also emerge as diseases in their own right. Considerable progress has been made in developing clinically relevant animal models for identifying the most significant underlying mech... | 10.1038/nrn2947 | This review provides a detailed and systematic account of the mechanisms that have been proposed to underlie abnormal pain states. |
10.1126/science.1127233 | 79,646,702 | Inflammation and trauma lead to enhanced pain sensitivity (hyperalgesia), which is in part due to altered sensory processing in the spinal cord. The synaptic hypothesis of hyperalgesia, which postulates that hyperalgesia is induced by the activity-dependent long-term potentiation (LTP) in the spinal cord, has been chal... | 10.1038/nrn2947 | The second of two studies from these authors that demonstrates a form of LTP in lamina I projection neurons — in this case, induced by activation of C fibres at a rate that occurs in physiological conditions. |
10.1073/pnas.1514282112 | 81,087,680 | Sour taste is detected by a subset of taste cells on the tongue and palate epithelium that respond to acids with trains of action potentials. Entry of protons through a Zn 2+ -sensitive proton conductance that is specific to sour taste cells has been shown to be the initial event in sour taste transduction. Whether thi... | 10.1038/nrn.2017.68 | This patch-clamp study shows that cytoplasmic acidification excites sour-sensing taste bud cells by blocking the inwardly rectifying K + channel KIR2.1. |
10.1126/science.1087155 | 20,375,725 | The tastes of sugars (sweet) and glutamate (umami) are thought to be detected by T1r receptors expressed in taste cells. Molecular genetics and heterologous expression implicate T1r2 plus T1r3 as a sweet-responsive receptor,and T1r1 plus T1r3,as well as a truncated form of the type 4 metabotropic glutamate receptor (ta... | 10.1038/nrn.2017.68 | This study shows that knockout of the gene that encodes T1R3 results in a selective loss of taste sensitivity to artificial sweeteners but does not abolish responses to sugars and umami (but see reference 21). |
10.1152/ajpregu.00433.2016 | 107,159,724 | The taste of sugar elicits cephalic-phase insulin release (CPIR), which limits the rise in blood glucose associated with meals. Little is known, however, about the gustatory mechanisms that trigger CPIR. We asked whether oral stimulation with any of the following taste stimuli elicited CPIR in mice: glucose, sucrose, m... | 10.1038/nrn.2017.68 | References 32 and 33 demonstrate the involvement of taste buds in stimulating insulin release immediately following sugar ingestion. The mechanism is independent of the sweet-taste receptors T1R2 and T1R3, and instead uses a transduction pathway similar to that used in pancreatic islet β cells. |
10.1038/ncomms9171 | 102,860,230 | Abstract Gustatory stimuli are detected by taste buds and transmitted to the hindbrain via sensory afferent neurons. Whether each taste quality (sweet, bitter and so on) is encoded by separate neurons (‘labelled lines’) remains controversial. We used mice expressing GCaMP3 in geniculate ganglion sensory neurons to inve... | 10.1038/nrn.2017.68 | This study uses Ca 2+ imaging in anaesthetized mice to show that gustatory afferent neurons respond to single or multiple taste quality stimuli depending on their concentration; this finding provides support for combinatorial taste coding (but see reference 141). |
10.1126/science.1118435 | 124,783,736 | Taste receptor cells detect chemicals in the oral cavity and transmit this information to taste nerves, but the neurotransmitter(s) have not been identified. We report that adenosine 5′-triphosphate (ATP) is the key neurotransmitter in this system. Genetic elimination of ionotropic purinergic receptors (P2X 2 and P2X 3... | 10.1038/nrn.2017.68 | The authors of this study identify ATP as a taste neurotransmitter that acts on P2X 2 and P2X 3 receptors expressed by sensory afferent fibres that innervate taste buds. |
10.1002/jemt.1070260304 | 82,524,565 | Abstract The fine structure of the taste buds of circumvallate papillae of two strains of mice was studied by electron microscopy. Mice anesthetized with ketamine were perfused through the heart with a double aldehyde mixture in cacodylate buffer and the tissues embedded in Epon. Semi‐serial sections were employed. The... | 10.1038/nrn.2017.68 | This is an early compilation of high-resolution electron micrographs that support current interpretations of the structure and function of the different types of taste cell that are described in this Review. |
10.1126/science.1080190 | 107,215,601 | The ability to taste the substance phenylthiocarbamide (PTC) has been widely used for genetic and anthropological studies, but genetic studies have produced conflicting results and demonstrated complex inheritance for this trait. We have identified a small region on chromosome 7q that shows strong linkage disequilibriu... | 10.1038/nrn.2017.68 | This genetic study identifies the human locus responsible for the inheritance of the taster and non-taster phenotypes for the bitter compound PTC. |
10.1126/science.6093258 | 101,372,079 | Learning behavior similar to vertebrate classical conditioning was demonstrated for the mollusc Hermissenda crassicornis . Postsynaptic membrane changes within well-defined neural systems that mediate the learning play a casual role in recording the learned association for later recall. Specific ionic currents in neura... | 10.1038/nrn1248 | The nudibranch mollusk Hermissenda was trained with a classical conditioning task where the animal's positive phototactic response was reduced after repeated pairings to rotation, an aversive stimulus. Training caused an increase in the intrinsic excitability of the type B photoreceptor neuron, which persisted for days... |
10.1523/jneurosci.23-32-10238.2003 | 101,373,411 | The cellular substrate for memory is generally attributed to long-lasting changes in synaptic strength. We report here that synaptic or pharmacological activation of the metabotropic glutamate receptor subtype 5 (mGluR5) induces long-term potentiation of intrinsic excitability (LTP-IE) in layer V pyramidal neurons. mGl... | 10.1038/nrn1248 | Synaptic or pharmacological activation of mGluR5 induced a persistent increase in intrinsic excitability of layer V pyramidal neurons. The increase was blocked and occluded by apamin, indicating that downregulation of SK channels mediates this process. Presentation of simulated EPSPs to the neurons with dynamic clampin... |
10.1101/gad.264303 | 61,364,672 | Streptomycetes exhibit a complex morphological differentiation. After a submerged mycelium has been formed, filaments grow into the air to septate into spores. A class of eight hydrophobic secreted proteins, ChpA–H, was shown to be instrumental in the development of Streptomyces coelicolor . Mature forms of ChpD–H are ... | 10.1038/nrmicro3546 | References 3 and 4 describe the first biochemical and genetic characterization of the chaplins, the major protein components of the hydrophobic sheath that allows growth into the air. |
10.1073/pnas.0404220101 | 102,590,517 | SapB is a morphogenetic peptide that is important for aerial mycelium formation by the filamentous bacterium Streptomyces coelicolor . Production of SapB commences during aerial mycelium formation and depends on most of the genes known to be required for the morphogenesis of aerial hyphae. Furthermore, the application ... | 10.1038/nrmicro3546 | The biochemical and genetic characterization of the surfactant peptide SapB, which first showed that it is structurally and biosynthetically related to a major class of peptide antibiotics. |
10.1128/mbio.00684-13 | 17,669,292 | ABSTRACT WhiA is a highly unusual transcriptional regulator related to a family of eukaryotic homing endonucleases. WhiA is required for sporulation in the filamentous bacterium Streptomyces , but WhiA homologues of unknown function are also found throughout the Gram-positive bacteria. To better understand the role of ... | 10.1038/nrmicro3546 | A characterization of the WhiA regulon, which showed that WhiA directly controls the initiation of sporulation septation. |
10.1111/j.1365-2958.2010.07338.x | 100,339,643 | Summary BldD is a transcriptional regulator essential for morphological development and antibiotic production in Streptomyces coelicolor . Here we identify the BldD regulon by means of chromatin immunoprecipitation‐microarray analysis (ChIP‐chip). The BldD regulon encompasses ∼167 transcriptional units, of which more t... | 10.1038/nrmicro3546 | The first clear recognition that BldD is at the top of the entire developmental regulatory cascade, acting as a master regulator to keep sporulation genes shut off during vegetative growth. |
10.1101/gad.600211 | 81,305,412 | In bacteria that divide by binary fission, cell division starts with the polymerization of the tubulin homolog FtsZ at mid-cell to form a cell division scaffold (the Z ring), followed by recruitment of the other divisome components. The current view of bacterial cell division control starts from the principle of negati... | 10.1038/nrmicro3546 | A study demonstrating that SsgA and SsgB have key roles in the positive placement of the FtsZ rings for sporulation septation in streptomycetes. |
10.1111/j.1365-2958.2012.08070.x | 100,337,598 | Summary The chaplin and rodlin proteins together constitute the major components of the hydrophobic sheath that coats the aerial hyphae and spores in Streptomyces , and mutants lacking the chaplins are unable to erect aerial hyphae and differentiate on minimal media. We have gained insight into the developmental regula... | 10.1038/nrmicro3546 | This study reveals that the key role of σ BldN in aerial hypha formation is to activate expression of the hydrophobic sheath proteins that allow growth into the air, and that σ BldN is in turn controlled by a transmembrane anti-sigma factor. |
10.1098/rsob.120097 | 78,548,068 | AdpA, one of the most pleiotropic transcription regulators in bacteria, controls expression of several dozen genes during Streptomyces differentiation. Here, we report a novel function for the AdpA protein: inhibitor of chromosome replication at the initiation stage. AdpA specifically recognizes the 5′ region of the St... | 10.1038/nrmicro3546 | A report showing that, in addition to functioning as a transcription factor, AdpA controls developmental chromosome replication by binding to two sites in the 5′ region of the origin of replication, oriC |
10.1111/j.1365-2958.2011.07795.x | 62,191,704 | Summary AdpA is a global transcriptional regulator that is induced by the microbial hormone A‐factor and activates many genes required for morphological differentiation and secondary metabolism in Streptomyces griseus . We confirmed that the regulatory tRNA gene bldA was required for translation of TTA‐containing adpA ... | 10.1038/nrmicro3546 | This study shows that the BldA tRNA forms a unique positive feedback loop with AdpA, in which AdpA activates transcription of bldA but BldA is also required for expression of AdpA because adpA has a TTA codon. |
10.1073/pnas.0913828107 | 105,379,842 | Cholesterol metabolism has been implicated in the pathogenesis of several neurodegenerative diseases, including the abnormal accumulation of amyloid-β, one of the pathological hallmarks of Alzheimer disease (AD). Acyl-CoA:cholesterol acyltransferases (ACAT1 and ACAT2) are two enzymes that convert free cholesterol to ch... | 10.1038/nrn3012 | This is a study that genetically validates the functional connection between ACAT and amyloid-β pathology in a mouse model. |
10.1073/pnas.95.11.6460 | 62,564,838 | The amyloid precursor protein (APP) plays a crucial role in the pathogenesis of Alzheimer’s disease. During intracellular transport APP undergoes a series of proteolytic cleavages that lead to the release either of an amyloidogenic fragment called β-amyloid (Aβ) or of a nonamyloidogenic secreted form consisting of the ... | 10.1038/nrn3012 | This is an original paper highlighting the role of cholesterol in the metabolism of APP. |
10.1073/pnas.0604954103 | 88,172,190 | Phosphatidylinositol 4,5-bisphosphate (PIP 2 ) is an important cellular effector whose functions include the regulation of ion channels and membrane trafficking. Aberrant PIP 2 metabolism has also been implicated in a variety of human disease states, e.g., cancer and diabetes. Here we report that familial Alzheimer's d... | 10.1038/nrn3012 | Along with reference 89, this study connects FAD-associated presenilin mutations with dysregulation of the PLC pathway and PtdIns(4,5)P 2 metabolism. |
10.1523/jneurosci.3317-10.2010 | 103,242,232 | Growing evidence implicates aberrant lipid signaling in Alzheimer's disease (AD). While phospholipases A2 and C have been recently shown to mediate key actions of amyloid β-peptide (Aβ) through a dysregulation of arachidonic acid and phosphatidylinositol-4,5-bisphosphate metabolism, respectively, the role of phospholip... | 10.1038/nrn3012 | This study shows an involvement of PLD2 in the synaptotoxic signalling pathway of amyloid-β using a mouse genetic model. |
10.1046/j.1365-2958.2003.03423.x | 41,131,707 | Summary Pseudomonas aeruginosa controls the production of many exoproteins and secondary metabolites via a hierarchical quorum sensing (QS) regulatory cascade involving the LuxR‐like proteins LasR, RhlR and their cognate signal molecules N ‐(3‐oxododecanoyl)‐ l ‐homoserine lactone (3O‐C12‐HSL) and N ‐(butanoyl)‐ l ‐hom... | 10.1038/nrmicro924 | The first report that QscR is present in several types of complex: as QscR multimers in the absence of AHL, lower-order QscR oligomers associated either with C4-HSL or 3O-C12-HSL and QscR-containing heterodimers with LasR or RhlR. |
10.1073/pnas.96.20.11229 | 82,815,133 | Numerous species of bacteria use an elegant regulatory mechanism known as quorum sensing to control the expression of specific genes in a cell-density dependent manner. In Gram-negative bacteria, quorum sensing systems function through a cell-to-cell signal molecule (autoinducer) that consists of a homoserine lactone w... | 10.1038/nrmicro924 | Describes the characterization of a novel QS signal molecule that is part of the Pseudomonas QS hierarchy. PQS production is regulated by the las system and PQS activity depends on the presence of the rhl system. (Also see references 70 and 71.) |
10.1046/j.1365-2958.2003.03422.x | 108,860,678 | Summary Of considerable interest in the biology of pathogenic bacteria are the mechanisms of intercellular signalling that can lead to the formation of persistent infections. In this article, we have examined the intracellular behaviour of a Pseudomonas aeruginosa quorum sensing regulator RhlR believed to be important ... | 10.1038/nrmicro924 | Describes the development of an assay based on the fluorescence anisotropy of EGFP fusion proteins that can be used to measure protein–protein and protein–nucleic acid interactions in vivo |
10.1073/pnas.022056699 | 40,329,940 | A signal turnover system is an essential component of many genetic regulatory mechanisms. The best-known example is the ubiquitin-dependent protein degradation system that exists in many organisms. We found that Agrobacterium tumefaciens adopts a unique signal turnover system to control exiting from a quorum-sensing mo... | 10.1038/nrmicro924 | Describes a signal-turnover system used by Agrobacterium tumefaciens to control exit from quorum-sensing regulation. |
10.1111/j.1460-9568.2004.03593.x | 19,151,543 | Abstract Fractalkine is a unique chemokine reported to be constitutively expressed by neurons. Its only receptor, CX3CR1, is expressed by microglia. Little is known about the expression of fractalkine and CX3CR1 in spinal cord. Given that peripheral nerve inflammation and/or injury gives rise to neuropathic pain, and n... | 10.1038/nrn1700 | The first paper to show that fractalkine release by neurons could be an activator of microglia. |
10.1073/pnas.0501634102 | 101,956,983 | Neuropathic pain remains a prevalent and persistent clinical problem because of our incomplete understanding of its pathogenesis. This study demonstrates for the first time, to our knowledge, a critical role for CNS innate immunity by means of microglial Toll-like receptor 4 (TLR4) in the induction phase of behavioral ... | 10.1038/nrn1700 | Showed, for the first time, the involvement of TLR4 in microglial activation in neuropathic pain models. |
10.1046/j.1351-5101.2003.00725.x | 121,838,307 | In spinal cord injury (SCI), pain is a major cause of disability. A review of experimental and human studies, which provide insight into the mechanisms and treatment of SCI neuropathic pain are presented. Each of a series of pathophysiologic changes after SCI may be relevant for the development of SCI neuropathic pain.... | 10.1038/nrn1700 | A good review about spinal cord injury and pain, with a useful section on different underlying mechanisms. |
10.1002/cne.901850102 | 81,031,358 | Abstract In our previous studies on spinal cord regeneration in the adult lizard and the newt, we observed that the radial processes of the regenerating ependyma form between them channels which are subsequently invaded by growing neurites. In the present study we compare embryogenesis of the newt spinal cord with rege... | 10.1038/nrn1326 | An important paper that first demonstrated the role of glial channels in providing a guidance highway for regenerating axons in the newt. |
10.1126/science.1072699 | 62,247,072 | In young animals, monocular deprivation leads to an ocular dominance shift, whereas in adults after the critical period there is no such shift. Chondroitin sulphate proteoglycans (CSPGs) are components of the extracellular matrix (ECM) inhibitory for axonal sprouting. We tested whether the developmental maturation of t... | 10.1038/nrn1326 | An important paper showing that CSPGs in the perineuronal net are a crucial part of the mechanism that controls synaptic plasticity in the adult CNS. |
10.1523/jneurosci.19-23-10417.1999 | 81,798,038 | Distinct brain peptidergic circuits govern peripheral energy homeostasis and related behavior. Here we report that mitochondrial uncoupling protein 2 (UCP2) is expressed discretely in neurons involved in homeostatic regulation. UCP2 protein was associated with the mitochondria of neurons, predominantly in axons and axo... | 10.1038/nrn1767 | Illustrates hypothalamic expression of UCP2 protein and establishes the putative role of UCP2 in producing local temperature gradients that may enhance synaptic function. |
10.1523/jneurosci.4269-04.2005 | 123,585,275 | Mitochondrial uncoupling proteins dissociate ATP synthesis from oxygen consumption in mitochondria and suppress free-radical production. We show that genetic manipulation of uncoupling protein-2 (UCP2) directly affects substantia nigra dopamine cell function. Overexpression of UCP2 increases mitochondrial uncoupling, w... | 10.1038/nrn1767 | The first report to show that UCP2-knockout mice are predisposed, whereas animals that overexpress UCP2 are resistant, to nigral neurodegeneration, probably owing to alterations in buffering in vivo ROS production. |
10.1146/annurev-pharmtox-061008-103222 | 18,958,063 | Interindividual variability in pain sensitivity and the response to analgesic manipulations remains a considerable clinical challenge as well as an area of intense scientific investigation. Techniques in this field have matured rapidly so that much relevant data have emerged only in the past few years. Our increasing u... | 10.1038/nrn2606 | The most current and comprehensive review of pain genetics in animals and humans. |
10.1126/science.6171034 | 123,066,698 | The origin, termination, and length of axonal growth after focal central nervous system injury was examined in adult rats by means of a new experimental model. When peripheral nerve segments were used as "bridges" between the medulla and spinal cord, axons from neurons at both these levels grew approximately 30 millime... | 10.1038/nrn1956 | A seminal paper that attributes axon regeneration failure to the non-permissive CNS environment by showing that some lesioned axons can regrow through a transplanted peripheral nerve graft. |
10.1126/science.1118313 | 79,420,872 | Nodes of Ranvier are regularly placed, nonmyelinated axon segments along myelinated nerves. Here we show that nodal membranes isolated from the central nervous system (CNS) of mammals restricted neurite outgrowth of cultured neurons. Proteomic analysis of these membranes revealed several inhibitors of neurite outgrowth... | 10.1038/nrn1956 | A unique study that provides a spatial explanation for how the myelin-associated inhibitor OMgp can limit collateral sprouting at nodes of Ranvier. |
10.1073/pnas.0409026102 | 41,448,601 | Axon regeneration failure in the adult mammalian CNS is attributed in part to the inhibitory nature of CNS myelin. Three myelin-associated, structurally distinct proteins, Nogo, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein, have been implicated in this inhibition. Neuronal Nogo receptor (NgR)... | 10.1038/nrn1956 | An important study showing that genetic deletion of NgR cannot overcome myelin inhibition or promote CST regeneration, supporting the presence of NgR-independent mechanisms mediating myelin inhibition and regeneration failure. |
10.1126/science.1072699 | 62,247,072 | In young animals, monocular deprivation leads to an ocular dominance shift, whereas in adults after the critical period there is no such shift. Chondroitin sulphate proteoglycans (CSPGs) are components of the extracellular matrix (ECM) inhibitory for axonal sprouting. We tested whether the developmental maturation of t... | 10.1038/nrn1956 | The first report describing the involvement of CSPGs in forming a perineuronal net that limits experience-driven plasticity in the adult. |
10.1126/science.1114362 | 20,702,845 | Monocular deprivation normally alters ocular dominance in the visual cortex only during a postnatal critical period (20 to 32 days postnatal in mice). We find that mutations in the Nogo-66 receptor (NgR) affect cessation of ocular dominance plasticity. In NgR –/– mice, plasticity during the critical period is normal, b... | 10.1038/nrn1956 | Another important paper that further demonstrates the parallels between CNS myelin and CSPGs. It shows that myelin-associated inhibitors, such as CSPGs, are also involved in critical period closure. |
10.1073/pnas.0405596101 | 4,819,298 | A critical early event in the HIV type 1 (HIV-1) particle assembly pathway is the targeting of the Gag protein to the site of virus assembly. In many cell types, assembly takes place predominantly at the plasma membrane. Cellular factors that regulate Gag targeting remain undefined. The phosphoinositide phosphatidylino... | 10.1038/nrmicro3490 | Demonstrates that the phospholipid PtdIns(4,5)P 2 plays a central part in directing Gag to the plasma membrane. |
10.1073/pnas.0602818103 | 62,071,872 | During the late phase of HIV type 1 (HIV-1) replication, newly synthesized retroviral Gag proteins are targeted to the plasma membrane of most hematopoietic cell types, where they colocalize at lipid rafts and assemble into immature virions. Membrane binding is mediated by the matrix (MA) domain of Gag, a 132-residue p... | 10.1038/nrmicro3490 | Provides structural evidence for a direct interaction between HIV-1 matrix and PtdIns(4,5)P 2 |
10.1073/pnas.88.8.3195 | 18,837,432 | Mutations in sequences at the C terminus of the capsid precursor protein of human immunodeficiency virus type 1 that affect the viral p6 protein prevent release of budded virus particles from the cell surface. The experiments reported here define an important step in the life cycle of the virus, the release of the budd... | 10.1038/nrmicro3490 | Shows for the first time that the p6 domain of HIV-1 Gag has a central role in virus release. |
10.1073/pnas.131059198 | 104,007,785 | Ubiquitination appears to be involved in virus particle release from infected cells. Free ubiquitin (Ub), as well as Ub covalently bound to a small fraction of p6 Gag, is detected in mature HIV particles. Here we report that the p6 region in the Pr55 Gag structural precursor polyprotein binds to Tsg101, a putative Ub r... | 10.1038/nrmicro3490 | Together with references 55–57, establishes the role for the ESCRT machinery in virus budding. |
10.1073/pnas.2234683100 | 103,228,974 | New HIV therapies are urgently needed to address the growing problem of drug resistance. In this article, we characterize the anti-HIV drug candidate 3- O -(3′,3′-dimethylsuccinyl) betulinic acid (PA-457). We show that PA-457 potently inhibits replication of both WT and drug-resistant HIV-1 isolates and demonstrate tha... | 10.1038/nrmicro3490 | Provides the first description of the mechanism of action of an HIV-1 maturation inhibitor. |
10.1073/pnas.97.1.343 | 122,648,490 | Lentiviruses, including HIV-1, have transmembrane envelope (Env) glycoproteins with cytoplasmic tails that are quite long compared with those of other retroviruses. However, mainly because of the lack of biochemical studies performed in cell types that are targets for HIV-1 infection, no clear consensus exists regardin... | 10.1038/nrmicro3490 | Demonstrates that the cytoplasmic tail of HIV-1 gp41 is required for Env incorporation in physiologically relevant cell types. |
10.1126/science.6159685 | 36,531,368 | Cytochemical staining of demyelinated peripheral axons revealed two types of axon membrane organization, one of which suggests that the demyelinated axolemma acquires a high density of sodium channels. Ferric ion-ferrocyanide stain was confined to a restricted region of axon membrane at the beginning of a demyelinated ... | 10.1038/nrn2023 | Together with reference 4, this paper showed reorganization of the demyelinated axon membrane, which acquires Na + channels in densities sufficient to support conduction. |
10.1002/ana.20045 | 26,994,005 | Abstract Axonal degeneration is a major cause of permanent neurological deficit in multiple sclerosis (MS), but no current therapies for the disease are known to be effective at axonal protection. Here, we examine the ability of a sodium channel–blocking agent, flecainide, to reduce axonal degeneration in an experiment... | 10.1038/nrn2023 | Along with reference 18, this paper demonstrates protection of axons in EAE with Na + channel blockers. |
10.1002/ana.10443 | 82,280,487 | Abstract Axonal degeneration can be an important cause of permanent disability in neurological disorders in which inflammation is prominent, including multiple sclerosis and Guillain–Barré syndrome. The mechanisms responsible for the degeneration remain unclear, but it is likely that axons succumb to factors produced a... | 10.1038/nrn2023 | Shows that Na + channel blockers protect axons from NO-induced injury. |
10.1073/pnas.090034797 | 17,576,707 | Voltage-gated sodium channels perform critical roles for electrical signaling in the nervous system by generating action potentials in axons and in dendrites. At least 10 genes encode sodium channels in mammals, but specific physiological roles that distinguish each of these isoforms are not known. One possibility is t... | 10.1038/nrn2023 | Demonstration that Nav1.6 is the predominant Na + channel at the nodes of Ranvier. |
10.1073/pnas.0402765101 | 19,711,272 | Although voltage-gated sodium channels are known to be deployed along experimentally demyelinated axons, the molecular identities of the sodium channels expressed along axons in human demyelinating diseases such as multiple sclerosis (MS) have not been determined. Here we demonstrate changes in the expression of sodium... | 10.1038/nrn2023 | Identifies the Na + channel isoforms along demyelinated axons in MS. |
10.1073/pnas.97.21.11598 | 21,550,346 | Clinical abnormalities in multiple sclerosis (MS) have classically been considered to be caused by demyelination and/or axonal degeneration; the possibility of molecular changes in neurons, such as the deployment of abnormal repertoires of ion channels that would alter neuronal electrogenic properties, has not been con... | 10.1038/nrn2023 | Demonstration of aberrant expression of the SNS Na + channel Nav1.8 in Purkinje cells in EAE and MS. |
10.1002/glia.20112 | 82,362,847 | Abstract Loss of axons is a major contributor to nonremitting deficits in the inflammatory demyelinating disease multiple sclerosis (MS). Based on biophysical studies showing that activity of axonal sodium channels can trigger axonal degeneration, recent studies have tested sodium channel‐blocking drugs in experimental... | 10.1038/nrn2023 | Demonstration of upregulated expression of Nav1.6 channels in microglia and macrophages in EAE and MS, and of their role in microglial/macrophage activation and phagocytosis. |
10.1523/jneurosci.14-01-00124.1994 | 58,973,147 | Embryonic Purkinje cells (PCs) from cerebellar primordia grafted in adult pcd mutant cerebellum replace missing PCs of the host, and become synaptically integrated into the defective cerebellar circuit. This process of neuronal replacement starts with the invasion of grafted PCs into the host cerebellum, and their radi... | 10.1038/nrn1957 | Together with reference 19, this suggests that adult differentiated CNS glia retain the ability to revert to the radial glia phenotype to guide endogenous or exogenous immature migrating neurons. |
10.1073/pnas.95.22.13248 | 41,303,240 | Members of the Eph family of tyrosine kinase receptors have been implicated in the regulation of developmental processes and, in particular, axon guidance in the developing nervous system. The function of the EphA4 (Sek1) receptor was explored through creation of a null mutant mouse. Mice with a null mutation in the Ep... | 10.1038/nrn1957 | One of the first publications to link CST development to specific guidance molecules. Also describes the 'kangaroo-like' gait displayed by mice with various mutations affecting CST development. |
10.1126/science.1079641 | 42,608,260 | Local circuits in the spinal cord that generate locomotion are termed central pattern generators (CPGs). These provide coordinated bilateral control over the normal limb alternation that underlies walking. The molecules that organize the mammalian CPG are unknown. Isolated spinal cords from mice lacking either the EphA... | 10.1038/nrn1957 | Previous papers (references 52 and 54) hinted that EphA4 or ephrin B3 knockout lead to a 'kangaroo-like' gait due to inappropriate CST midline crossing. Surprisingly, this paper demonstrates that the phenotype of these mice actually stems from aberrant crossing of segmental local interneurons within the CPG, rather tha... |
10.1152/jn.1998.79.3.1329 | 20,799,404 | de Leon, R. D., J. A. Hodgson, R. R. Roy, and V. R. Edgerton. Locomotor capacity attributable to step training versus spontaneous recovery after spinalization in adult cats. J. Neurophysiol. 79: 1329–1340, 1998. Locomotor performance, hindlimb muscle activity and gait patterns during stepping were studied in step-train... | 10.1038/nrn1957 | One of many publications from the Edgerton group emphasizing the improved plasticity of intrinsic spinal cord circuits that is achieved with sensorimotor feedback training. |
10.1126/science.1072699 | 62,247,072 | In young animals, monocular deprivation leads to an ocular dominance shift, whereas in adults after the critical period there is no such shift. Chondroitin sulphate proteoglycans (CSPGs) are components of the extracellular matrix (ECM) inhibitory for axonal sprouting. We tested whether the developmental maturation of t... | 10.1038/nrn1957 | Using both immunohistological and functional techniques, together with reference 96, the authors begin to elucidate the molecular mechanisms of ocular dominance plasticity, identifying the key roles of CSPGs and MAIs. |
10.1002/dvdy.10226 | 100,364,907 | Abstract Lower vertebrates, such as fish and amphibians, and developing higher vertebrates can regenerate complex body structures, including significant portions of their central nervous system. It is still poorly understood why this potential is lost with evolution and development and becomes very limited in adult mam... | 10.1038/nrn1957 | An interesting review that goes into more depth on the cellular and molecular mechanisms underlying the starkly contrasting ability of lower versus higher vertebrates to regenerate the injured CNS. |
10.1126/science.6171034 | 123,066,698 | The origin, termination, and length of axonal growth after focal central nervous system injury was examined in adult rats by means of a new experimental model. When peripheral nerve segments were used as "bridges" between the medulla and spinal cord, axons from neurons at both these levels grew approximately 30 millime... | 10.1038/nrn1957 | One of a series of papers from Aguayo's group that revives work that was first performed by Tello and Ramón y Cajal, demonstrating that CNS axons can indeed regenerate if provided with a permissive environment. |
10.1523/jneurosci.2828-04.2004 | 123,258,224 | The growth of injured axons in the adult mammalian CNS is limited after injury. Three myelin proteins, Nogo, MAG (myelin-associated glycoprotein), and OMgp (oligodendrocyte myelin glycoprotein), bind to the Nogo-66 receptor (NgR) and inhibit axonal growth in vitro . Transgenic or viral blockade of NgR function allows a... | 10.1038/nrn1957 | Shows that blocking the receptor for three major MAIs enhances CST regeneration following SCI, but growth is limited and proceeds along ectopic pathways. |
10.1002/ana.20627 | 39,964,990 | Abstract Spinal cord trauma leads to loss of motor, sensory and autonomic functions below the lesion. Recovery is very restricted, due in part to neurite growth inhibitory myelin proteins, in particular Nogo‐A. Two neutralizing antibodies against Nogo‐A were used to study recovery and axonal regeneration after spinal c... | 10.1038/nrn1957 | Shows that the blockade of Nogo-A's unique amino-terminal domain also improves axon regeneration, again in a limited, non-fasciculated pattern. |
10.1002/jnr.10457 | 103,064,144 | Abstract Ephrins and Eph receptors are a family of molecules that have been implicated in axonal pathfinding. A unique feature of B‐class ephrins and Eph receptors is their ability to transmit bidirectional signals in both ephrin‐ and Eph receptor‐expressing cells upon cell–cell contact. These signals can lead to cytos... | 10.1038/nrn1957 | A comprehensive comparison of ephrin/Eph expression in the neonatal versus adult mouse CNS. |
10.1111/j.1460-9568.2004.03428.x | 62,147,566 | Abstract Fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGL) catalyse the hydrolysis of the endocannabinoids anandamide and 2‐arachidonoyl glycerol. We investigated their ultrastructural distribution in brain areas where the localization and effects of cannabinoid receptor activation are known. In the hipp... | 10.1038/nrn4004 | One of the first studies to characterize the cellular location of the eCB metabolic enzymes, thereby emphasizing potentially distinct influences of AEA and 2-AG processing on synaptic function. |
10.1111/j.1530-0277.2012.01815.x | 16,611,937 | Background Several lines of evidence link cannabinoid ( CB ) type 1 ( CB 1 ) receptor‐mediated endogenous CB (e CB ) signaling to the etiology of alcohol dependence ( AD ). However, to date, only peripheral measures of e CB function have been collected in living humans with AD and no human in vivo data on the potential... | 10.1038/nrn4004 | This study was among the first to demonstrate altered brain CB1R availability in humans with alcoholism. |
10.1159/000338642 | 38,417,808 | CB1 and CB2 receptors are influenced via exogenous and endogenous cannabinoids. To date, little is known regarding changes in receptor expression and methylation in THC (tetrahydrocannabinol) dependence. Therefore, the CB1 and CB2 receptor mRNA expression levels and promoter methylation status in the peripheral blood c... | 10.1038/nrn4004 | The first study to report epigenetic differences in CNR1 , demonstrating alteration of DNA methylation status (in peripheral blood cells) correlated with CB1R expression. |
10.1073/pnas.76.3.1497 | 107,948,117 | Inactivation of the Ca channel of Aplysia neurons was studied in the absence of potassium current in cells that were cesium-loaded with the aid of the ionophore nystatin. Inactivation was substantially decreased by methods that limited Ca entry. Depolarizations commensurate with the equilibrium potential of Ca resulted... | 10.1038/nrn959 | References 4 and 5 are pioneering descriptions of CDI in Paramecium and molluscan neurons, and have directed the study of Ca 2+ channels towards the analysis of localized Ca 2+ signalling. |
10.1113/jphysiol.1991.sp018581 | 27,008,978 | 1. The process of inactivation of the Ca2+ current of acutely dissociated pyramidal cells from the CA1 subfield of mature guinea‐pig hippocampus was characterized. The decline of the current after rapid activation could be approximated well by the sum of two exponentials (time constants approximately 200 ms and 2 s) an... | 10.1038/nrn959 | This monograph provides a comprehensive analysis of native Ca 2+ current inactivation in central neurons, and points to the importance of local Ca 2+ domains for CDI. |
10.1113/jphysiol.1986.sp016206 | 27,029,419 | 'Wash‐out' and inactivation of the Ca current were examined in dialysed, voltage‐clamped neurones of Helix aspersa under conditions that isolate the Ca current virtually free of other currents. EGTA or other internal Ca2+ chelators were routinely omitted from the dialysate. The time‐dependent loss, or wash‐out, of Ca c... | 10.1038/nrn959 | This pioneering work provided the first mechanistic explanation for CDI in neurons. |
10.1523/jneurosci.17-18-06961.1997 | 125,114,435 | Immobile and mobile calcium buffers shape the calcium signal close to a channel by reducing and localizing the transient calcium increase to physiological compartments. In this paper, we focus on the impact of mobile buffers in shaping steady-state calcium gradients in the vicinity of an open channel, i.e. within its “... | 10.1038/nrn959 | This theoretical paper describes the development of standing Ca 2+ gradients within hundreds of microseconds and a few hundred nanometres after Ca 2+ channel opening. In addition, it shows that every Ca 2+ buffer can be assigned a uniquely defined length constant as a measure of its ability to buffer calcium close to t... |
10.1126/science.270.5241.1502 | 3,718,959 | Intracellular calcium (Ca 2+ ) inhibits the opening of L-type (α 1C ) Ca 2+ channels, providing physiological control of Ca 2+ entry into a wide variety of cells. A structural determinant of this Ca 2+ -sensitive inactivation was revealed by chimeric Ca 2+ channels derived from parental α 1C and α 1E channels, the latt... | 10.1038/nrn959 | This paper provided the first indication of the importance of the carboxy-terminal region of L-type Ca 2+ channels for CDI. |
10.1126/science.293.5527.98 | 39,317,182 | The existence of a large number of receptors coupled to heterotrimeric guanine nucleotide binding proteins (G proteins) raises the question of how a particular receptor selectively regulates specific targets. We provide insight into this question by identifying a prototypical macromolecular signaling complex. The β 2 a... | 10.1038/nrn959 | This paper impressively shows the existence of large multi-protein signalling complexes in mammalian central neurons, which provide highly localized, specific and rapid signalling by G-protein-coupled receptors. |
10.1523/jneurosci.20-05-01831.2000 | 103,171,356 | In mesial temporal lobe epilepsy (mTLE), the predominant form of epilepsy in adults, and in animal models of the disease, there is a conspicuous loss of the intracellular Ca 2+ -binding protein calbindin-D 28k (CB) from granule cells (GCs) of the dentate gyrus. The role of this protein in nerve cell function is controv... | 10.1038/nrn959 | This paper points to the possible neuroprotective role of CDI in temporal lobe epilepsy, and highlights the ability of exogenous calbindin-D 28k to disrupt the CDI mechanism in hippocampal neurons. |
10.1073/pnas.96.4.1680 | 104,093,768 | Neuroimaging studies have shown differential amygdala responses to masked (“unseen”) emotional stimuli. How visual signals related to such unseen stimuli access the amygdala is unknown. A possible pathway, involving the superior colliculus and pulvinar, is suggested by observations of patients with striate cortex lesio... | 10.1038/nrn728 | Presented evidence for the existence of a subcortical CS transmission route to the amygdala in the human brain, mirroring the findings in rats. |
10.1046/j.0953-816x.2001.01570.x | 102,585,865 | Abstract Long‐term depression (LTD) at parallel fibre–Purkinje cell synapse of the cerebellum is thought to be a cellular substrate for motor learning. LTD requires activation of metabotropic glutamate receptor subtype 1 (mGluR1) and its downstream signalling pathways, which invariably involves phospholipase Cβs (PLCβs... | 10.1038/nrn728 | In contrast to the pcd mice (Reference 140 ), mice with deficient cerebellar LTD could not learn the conditioned eyelid response, even though other properties of the granule-to-Purkinje synapse seemed to be normal. |
10.1002/pmic.200600756 | 80,932,641 | Abstract Human cerebrospinal fluid (CSF) is an important source for studying protein biomarkers of age‐related neurodegenerative diseases. Before characterizing biomarkers unique to each disease, it is necessary to categorize CSF proteins systematically and extensively. However, the enormous complexity, great dynamic r... | 10.1038/nrn2701 | Study reporting the largest catalogue of the human CSF proteome, an important source of biomarkers. |
10.1126/scisignal.2000102 | 28,238,769 | Analysis of protein phosphorylation patterns provides insight into the organization of molecular networks at the postsynaptic density. | 10.1038/nrn2701 | Synapse phosphoproteomics reveals a high degree of complexity and combination of methods to generate the first site-specific phosphorylation map of a proteome. |
10.1126/science.1100907 | 83,055,769 | When humans are offered the choice between rewards available at different points in time, the relative values of the options are discounted according to their expected delays until delivery. Using functional magnetic resonance imaging, we examined the neural correlates of time discounting while subjects made a series o... | 10.1038/nrn2682 | A study in which the authors propose that two competing systems, that is, the prefrontal cortex and the subcortical striatum, underlie the computation of the immediate and delayed value. |
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