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Showing papers in "Nature Neuroscience in 2003"


Journal ArticleDOI
TL;DR: The results provide the first quantitative demonstration of reliable inference of anatomical connectivity between human gray matter structures using diffusion data and the first connectivity-based segmentation of gray matter.
Abstract: Evidence concerning anatomical connectivities in the human brain is sparse and based largely on limited post-mortem observations. Diffusion tensor imaging has previously been used to define large white-matter tracts in the living human brain, but this technique has had limited success in tracing pathways into gray matter. Here we identified specific connections between human thalamus and cortex using a novel probabilistic tractography algorithm with diffusion imaging data. Classification of thalamic gray matter based on cortical connectivity patterns revealed distinct subregions whose locations correspond to nuclei described previously in histological studies. The connections that we found between thalamus and cortex were similar to those reported for non-human primates and were reproducible between individuals. Our results provide the first quantitative demonstration of reliable inference of anatomical connectivity between human gray matter structures using diffusion data and the first connectivity-based segmentation of gray matter.

2,296 citations


Journal ArticleDOI
TL;DR: A significant, nonlinear decline in GMD with age is found over dorsal frontal and parietal association cortices on both the lateral and interhemispheric surfaces, indicating that the posterior temporal cortices have a more protracted course of maturation than any other cortical region.
Abstract: We used magnetic resonance imaging and cortical matching algorithms to map gray matter density (GMD) in 176 normal individuals ranging in age from 7 to 87 years. We found a significant, nonlinear decline in GMD with age, which was most rapid between 7 and about 60 years, over dorsal frontal and parietal association cortices on both the lateral and interhemispheric surfaces. Age effects were inverted in the left posterior temporal region, where GMD gain continued up to age 30 and then rapidly declined. The trajectory of maturational and aging effects varied considerably over the cortex. Visual, auditory and limbic cortices, which are known to myelinate early, showed a more linear pattern of aging than the frontal and parietal neocortices, which continue myelination into adulthood. Our findings also indicate that the posterior temporal cortices, primarily in the left hemisphere, which typically support language functions, have a more protracted course of maturation than any other cortical region.

2,233 citations


Journal ArticleDOI
TL;DR: This work uses a new observer-independent method to relate the degree of damage within a specific prefrontal region to performance on a stop-signal task that is sensitive to the neurodevelopmental aspects of stopping behavior and to attention-deficit/hyperactivity disorder (ADHD) as well as its amelioration by methylphenidate.
Abstract: The precise localization of executive functions such as response inhibition within the prefrontal cortex (PFC), although theoretically crucial, has proven to be controversial and difficult1. Functional neuroimaging has contributed importantly to this debate1,2,3,4,5,6,7, but as human cortical lesions are seldom discrete, the literature still lacks definitive neuropsychological evidence that a specific region is necessary for task performance. We overcame this limitation by using a new observer-independent method to relate the degree of damage within a specific prefrontal region to performance on a stop-signal task that is sensitive to the neurodevelopmental aspects of stopping behavior2 and to attention-deficit/hyperactivity disorder (ADHD) as well as its amelioration by methylphenidate5,8.

1,653 citations


Journal ArticleDOI
TL;DR: In vivo blockade of glutamate-mediated [Ca2+]i elevations in astrocytes reduced the blood flow increase in the somatosensory cortex during contralateral forepaw stimulation and showed that neuron-to-astrocyte signaling is a key mechanism in functional hyperemia.
Abstract: The cellular mechanisms underlying functional hyperemia--the coupling of neuronal activation to cerebral blood vessel responses--are not yet known. Here we show in rat cortical slices that the dilation of arterioles triggered by neuronal activity is dependent on glutamate-mediated [Ca(2+)](i) oscillations in astrocytes. Inhibition of these Ca(2+) responses resulted in the impairment of activity-dependent vasodilation, whereas selective activation--by patch pipette--of single astrocytes that were in contact with arterioles triggered vessel relaxation. We also found that a cyclooxygenase product is centrally involved in this astrocyte-mediated control of arterioles. In vivo blockade of glutamate-mediated [Ca(2+)](i) elevations in astrocytes reduced the blood flow increase in the somatosensory cortex during contralateral forepaw stimulation. Taken together, our findings show that neuron-to-astrocyte signaling is a key mechanism in functional hyperemia.

1,409 citations


Journal ArticleDOI
TL;DR: VLSM maps for measures of speech fluency and language comprehension in 101 left-hemisphere-damaged aphasic patients confirm the anticipated contrast between anterior and posterior areas and indicate that interacting regions facilitate Fluency and auditory comprehension, in agreement with findings from modern brain imaging.
Abstract: For more than a century, lesion–symptom mapping studies have yielded valuable insights into the relationships between brain and behavior, but newer imaging techniques have surpassed lesion analysis in examining functional networks. Here we used a new method—voxel-based lesion–symptom mapping (VLSM)—to analyze the relationship between tissue damage and behavior on a voxel-by-voxel basis, as in functional neuroimaging. We applied VLSM to measures of speech fluency and language comprehension in 101 left-hemisphere-damaged aphasic patients: the VLSM maps for these measures confirm the anticipated contrast between anterior and posterior areas, and they also indicate that interacting regions facilitate fluency and auditory comprehension, in agreement with findings from modern brain imaging.

1,259 citations


Journal ArticleDOI
TL;DR: This framework offers a coherent scheme for explaining the neural correlates of (visual) consciousness in terms of competing cellular assemblies and outlines some general experimental approaches to the problem.
Abstract: Here we summarize our present approach to the problem of consciousness. After an introduction outlining our general strategy, we describe what is meant by the term 'framework' and set it out under ten headings. This framework offers a coherent scheme for explaining the neural correlates of (visual) consciousness in terms of competing cellular assemblies. Most of the ideas we favor have been suggested before, but their combination is original. We also outline some general experimental approaches to the problem and, finally, acknowledge some relevant aspects of the brain that have been left out of the proposed framework.

1,238 citations


Journal ArticleDOI
TL;DR: It is shown that combinations of three time-varying muscle synergies underlie the variety of muscle patterns required to kick in different directions, that the recruitment of these synergies is related to movement kinematics, and that there are similarities among the synergies extracted from different behaviors.
Abstract: A central issue in motor control is how the central nervous system generates the muscle activity patterns necessary to achieve a variety of behavioral goals. The many degrees of freedom of the musculoskeletal apparatus provide great flexibility but make the control problem extremely complex. Muscle synergies—coherent activations, in space or time, of a group of muscles—have been proposed as building blocks that could simplify the construction of motor behaviors. To evaluate this hypothesis, we developed a new method to extract invariant spatiotemporal components from the simultaneous recordings of the activity of many muscles. We used this technique to analyze the muscle patterns of intact and unrestrained frogs during kicking, a natural defensive behavior. Here we show that combinations of three time-varying muscle synergies underlie the variety of muscle patterns required to kick in different directions, that the recruitment of these synergies is related to movement kinematics, and that there are similarities among the synergies extracted from different behaviors.

1,158 citations


Journal ArticleDOI
TL;DR: This review focuses on syntax, using recent neuroimaging data and cognitive theory to propose a specific point of convergence between syntactic processing in language and music, which leads to testable predictions, including the prediction that that syntactic comprehension problems in Broca's aphasia are not selective to language but influence music perception as well.
Abstract: The comparative study of music and language is drawing an increasing amount of research interest. Like language, music is a human universal involving perceptually discrete elements organized into hierarchically structured sequences. Music and language can thus serve as foils for each other in the study of brain mechanisms underlying complex sound processing, and comparative research can provide novel insights into the functional and neural architecture of both domains. This review focuses on syntax, using recent neuroimaging data and cognitive theory to propose a specific point of convergence between syntactic processing in language and music. This leads to testable predictions, including the prediction that that syntactic comprehension problems in Broca's aphasia are not selective to language but influence music perception as well.

1,089 citations


Journal ArticleDOI
TL;DR: Dissociable regulation of dopamine neuron discharge by two separate afferent systems in rats is reported; inhibition of pallidal afferents selectively increased the population activity of dopamine neurons, whereas activation of pedunculopontine inputs increased burst firing.
Abstract: The mesolimbic dopamine system is centrally involved in reward and goal-directed behavior, and it has been implicated in multiple psychiatric disorders. Understanding the mechanism by which dopamine participates in these activities requires comprehension of the dynamics of dopamine release. Here we report dissociable regulation of dopamine neuron discharge by two separate afferent systems in rats; inhibition of pallidal afferents selectively increased the population activity of dopamine neurons, whereas activation of pedunculopontine inputs increased burst firing. Only the increase in population activity increased ventral striatal dopamine efflux. After blockade of dopamine reuptake, however, enhanced bursting increased dopamine efflux three times more than did enhanced population activity. These results provide insight into multiple regulatory systems that modulate dopamine system function: burst firing induces massive synaptic dopamine release, which is rapidly removed by reuptake before escaping the synaptic cleft, whereas increased population activity modulates tonic extrasynaptic dopamine levels that are less influenced by reuptake.

1,076 citations


Journal ArticleDOI
TL;DR: An activation of pulvinar and superior colliculus by fearful expressions occurred specifically with low-frequency faces, suggesting that these subcortical pathways may provide coarse fear-related inputs to the amygdala.
Abstract: High and low spatial frequency information in visual images is processed by distinct neural channels. Using event-related functional magnetic resonance imaging (fMRI) in humans, we show dissociable roles of such visual channels for processing faces and emotional fearful expressions. Neural responses in fusiform cortex, and effects of repeating the same face identity upon fusiform activity, were greater with intact or high-spatial-frequency face stimuli than with low-frequency faces, regardless of emotional expression. In contrast, amygdala responses to fearful expressions were greater for intact or low-frequency faces than for high-frequency faces. An activation of pulvinar and superior colliculus by fearful expressions occurred specifically with low-frequency faces, suggesting that these subcortical pathways may provide coarse fear-related inputs to the amygdala.

1,062 citations


Journal ArticleDOI
TL;DR: Multiple regression analyses indicated that lateral prefrontal and parietal regions may mediate the relation between ability (gF) and performance (accuracy despite interference), providing constraints on the neural mechanisms that support gF.
Abstract: We used an individual-differences approach to test whether general fluid intelligence (gF) is mediated by brain regions that support attentional (executive) control, including subregions of the prefrontal cortex. Forty-eight participants first completed a standard measure of gF (Raven's Advanced Progressive Matrices). They then performed verbal and nonverbal versions of a challenging working-memory task (three-back) while their brain activity was measured using functional magnetic resonance imaging (fMRI). Trials within the three-back task varied greatly in the demand for attentional control because of differences in trial-to-trial interference. On high-interference trials specifically, participants with higher gF were more accurate and had greater event-related neural activity in several brain regions. Multiple regression analyses indicated that lateral prefrontal and parietal regions may mediate the relation between ability (gF) and performance (accuracy despite interference), providing constraints on the neural mechanisms that support gF.

Journal ArticleDOI
TL;DR: Using event-related functional magnetic resonance imaging (fMRI), it is found amygdala activation to be associated with intensity, and not valence, of odors, suggesting that the affective representations of intensity and valence draw upon dissociable neural substrates.
Abstract: Affective experience has been described in terms of two primary dimensions: intensity and valence. In the human brain, it is intrinsically difficult to dissociate the neural coding of these affective dimensions for visual and auditory stimuli, but such dissociation is more readily achieved in olfaction, where intensity and valence can be manipulated independently. Using event-related functional magnetic resonance imaging (fMRI), we found amygdala activation to be associated with intensity, and not valence, of odors. Activity in regions of orbitofrontal cortex, in contrast, were associated with valence independent of intensity. These findings show that distinct olfactory regions subserve the analysis of the degree and quality of olfactory stimulation, suggesting that the affective representations of intensity and valence draw upon dissociable neural substrates.

Journal ArticleDOI
TL;DR: It is reported that neurons in cat primary auditory cortex (A1) responded more strongly to a rarely presented sound than to the same sound when it was common, indicating that A1 neurons, in addition to processing the acoustic features of sounds, may also be involved in sensory memory and novelty detection.
Abstract: The ability to detect rare auditory events can be critical for survival. We report here that neurons in cat primary auditory cortex (A1) responded more strongly to a rarely presented sound than to the same sound when it was common. For the rare stimuli, we used both frequency and amplitude deviants. Moreover, some A1 neurons showed hyperacuity for frequency deviants--a frequency resolution one order of magnitude better than receptive field widths in A1. In contrast, auditory thalamic neurons were insensitive to the probability of frequency deviants. These phenomena resulted from stimulus-specific adaptation in A1, which may be a single-neuron correlate of an extensively studied cortical potential--mismatch negativity--that is evoked by rare sounds. Our results thus indicate that A1 neurons, in addition to processing the acoustic features of sounds, may also be involved in sensory memory and novelty detection.

Journal ArticleDOI
TL;DR: It is found that activity regulates postsynaptic composition and signaling through the ubiquitin-proteasome system, providing a mechanistic link between synaptic activity, protein turnover and the functional reorganization of synapses.
Abstract: Experience-dependent remodeling of the postsynaptic density (PSD) is critical for synapse formation and plasticity in the mammalian brain. Here, in cultured rat hippocampal neurons, I found long-lasting, global changes in the molecular composition of the PSD dictated by synaptic activity. These changes were bidirectional, reversible, modular, and involved multiple classes of PSD proteins. Moreover, activity-dependent remodeling was accompanied by altered protein turnover, occurred with corresponding increases or decreases in ubiquitin conjugation of synaptic proteins and required proteasome-mediated degradation. These modifications, in turn, reciprocally altered synaptic signaling to the downstream effectors CREB (cyclic AMP response element binding protein) and ERK-MAPK (extracellular signal regulated kinase-MAP kinase). These results indicate that activity regulates postsynaptic composition and signaling through the ubiquitin-proteasome system, providing a mechanistic link between synaptic activity, protein turnover and the functional reorganization of synapses.

Journal ArticleDOI
TL;DR: It is found that PKA phosphorylation of the AMPA receptor subunits GluR4 and GLUR1 directly controlled the synaptic incorporation of AMPA receptors in organotypic slices from rat hippocampus.
Abstract: The regulated incorporation of AMPA receptors into synapses is important for synaptic plasticity. Here we examine the role of protein kinase A (PKA) in this process. We found that PKA phosphorylation of the AMPA receptor subunits GluR4 and GluR1 directly controlled the synaptic incorporation of AMPA receptors in organotypic slices from rat hippocampus. Activity-driven PKA phosphorylation of GluR4 was necessary and sufficient to relieve a retention interaction and drive receptors into synapses. In contrast, PKA phosphorylation of GluR1 and the activity of calcium/calmodulin-dependent kinase II (CaMKII) were both necessary for receptor incorporation. Thus, PKA phosphorylation of AMPA receptor subunits contributes to diverse mechanisms underlying synaptic plasticity.

Journal ArticleDOI
TL;DR: It is reported that BDNF is expressed at high levels in the ventromedial hypothalamus (VMH) where its expression is regulated by nutritional state and by MC4R signaling, and this results show that MC 4R signaling controls BDNF expression in the VMH.
Abstract: The melanocortin-4 receptor (MC4R) is critically involved in regulating energy balance, and obesity has been observed in mice with mutations in the gene for brain-derived neurotrophic factor (BDNF). Here we report that BDNF is expressed at high levels in the ventromedial hypothalamus (VMH) where its expression is regulated by nutritional state and by MC4R signaling. In addition, similar to MC4R mutants, mouse mutants that expresses the BDNF receptor TrkB at a quarter of the normal amount showed hyperphagia and excessive weight gain on higher-fat diets. Furthermore, BDNF infusion into the brain suppressed the hyperphagia and excessive weight gain observed on higher-fat diets in mice with deficient MC4R signaling. These results show that MC4R signaling controls BDNF expression in the VMH and support the hypothesis that BDNF is an important effector through which MC4R signaling controls energy balance.

Journal ArticleDOI
TL;DR: The results show that newly born cells recruited into the olfactory bulb become neurons, and a unique sequence of events leads to their functional integration.
Abstract: New neurons are continually recruited throughout adulthood in certain regions of the adult mammalian brain. How these cells mature and integrate into preexisting functional circuits remains unknown. Here we describe the physiological properties of newborn olfactory bulb interneurons at five different stages of their maturation in adult mice. Patch-clamp recordings were obtained from tangentially and radially migrating young neurons and from neurons in three subsequent maturation stages. Tangentially migrating neurons expressed extrasynaptic GABAA receptors and then AMPA receptors, before NMDA receptors appeared in radially migrating neurons. Spontaneous synaptic activity emerged soon after migration was complete, and spiking activity was the last characteristic to be acquired. This delayed excitability is unique to cells born in the adult and may protect circuits from uncontrolled neurotransmitter release and neural network disruption. Our results show that newly born cells recruited into the olfactory bulb become neurons, and a unique sequence of events leads to their functional integration.

Journal ArticleDOI
TL;DR: The identification of a variant of the apolipoprotein E (APOE) gene as a major genetic risk factor for AD is also consistent with a role for cholesterol in the pathogenesis of AD.
Abstract: A hallmark of all forms of Alzheimer's disease (AD) is an abnormal accumulation of the beta-amyloid protein (Abeta) in specific brain regions. Both the generation and clearance of Abeta are regulated by cholesterol. Elevated cholesterol levels increase Abeta in cellular and most animals models of AD, and drugs that inhibit cholesterol synthesis lower Abeta in these models. Recent studies show that not only the total amount, but also the distribution of cholesterol within neurons, impacts Abeta biogenesis. The identification of a variant of the apolipoprotein E (APOE) gene as a major genetic risk factor for AD is also consistent with a role for cholesterol in the pathogenesis of AD. Clinical trials have recently been initiated to test whether lowering plasma and/or neuronal cholesterol levels is a viable strategy for treating and preventing AD. In this review, we describe recent findings concerning the molecular mechanisms underlying the cholesterol-AD connection.

Journal ArticleDOI
TL;DR: It is reported that expression of the transcription factors Sox1, Sox2 and Sox3 (Sox1–3) is a critical determinant of neurogenesis and the generation of neurons from stem cells depends on the inhibition of Sox1-3 expression by proneural proteins.
Abstract: The generation of neurons from stem cells involves the activity of proneural basic helix-loop-helix (bHLH) proteins, but the mechanism by which these proteins irreversibly commit stem cells to neuronal differentiation is not known. Here we report that expression of the transcription factors Sox1, Sox2 and Sox3 (Sox1-3) is a critical determinant of neurogenesis. Using chick in ovo electroporation, we found that Sox1-3 transcription factors keep neural cells undifferentiated by counteracting the activity of proneural proteins. Conversely, the capacity of proneural bHLH proteins to direct neuronal differentiation critically depends on their ability to suppress Sox1-3 expression in CNS progenitors. These data suggest that the generation of neurons from stem cells depends on the inhibition of Sox1-3 expression by proneural proteins.

Journal ArticleDOI
TL;DR: Investigation of the hypothesis that task performance can rapidly and adaptively reshape cortical receptive field properties in accord with specific task demands and salient sensory cues found that attending to a specific target frequency during the detection task consistently induced localized facilitative changes in STRF shape.
Abstract: We investigated the hypothesis that task performance can rapidly and adaptively reshape cortical receptive field properties in accord with specific task demands and salient sensory cues. We recorded neuronal responses in the primary auditory cortex of behaving ferrets that were trained to detect a target tone of any frequency. Cortical plasticity was quantified by measuring focal changes in each cell's spectrotemporal response field (STRF) in a series of passive and active behavioral conditions. STRF measurements were made simultaneously with task performance, providing multiple snapshots of the dynamic STRF during ongoing behavior. Attending to a specific target frequency during the detection task consistently induced localized facilitative changes in STRF shape, which were swift in onset. Such modulatory changes may enhance overall cortical responsiveness to the target tone and increase the likelihood of 'capturing' the attended target during the detection task. Some receptive field changes persisted for hours after the task was over and hence may contribute to long-term sensory memory.

Journal ArticleDOI
TL;DR: Results indicate that abnormal information storage in corticostriatal synapses is linked with the development of L-DOPA–induced dyskinesia.
Abstract: Long-term treatment with the dopamine precursor levodopa (L-DOPA) induces dyskinesia in Parkinson's disease (PD) patients We divided hemiparkinsonian rats treated chronically with L-DOPA into two groups: one showed motor improvement without dyskinesia, and the other developed debilitating dyskinesias in response to the treatment We then compared the plasticity of corticostriatal synapses between the two groups High-frequency stimulation of cortical afferents induced long-term potentiation (LTP) of corticostriatal synapses in both groups of animals Control and non-dyskinetic rats showed synaptic depotentiation in response to subsequent low-frequency synaptic stimulation, but dyskinetic rats did not The depotentiation seen in both L-DOPA-treated non-dyskinetic rats and intact controls was prevented by activation of the D1 subclass of dopamine receptors or inhibition of protein phosphatases The striata of dyskinetic rats contained abnormally high levels of phospho[Thr34]-DARPP-32, an inhibitor of protein phosphatase 1 These results indicate that abnormal information storage in corticostriatal synapses is linked with the development of L-DOPA-induced dyskinesia

Journal ArticleDOI
TL;DR: This work identifies Sonic hedgehog (Shh) as a regulator of adult hippocampal neural stem cells and finds high expression of the Shh receptor Patched in both the adult rat hippocampus and neural progenitor cells isolated from this region.
Abstract: Neural stem cells exist in the developing and adult nervous systems of all mammals, but the basic mechanisms that control their behavior are not yet well understood. Here, we investigated the role of Sonic hedgehog (Shh), a factor vital for neural development, in regulating adult hippocampal neural stem cells. We found high expression of the Shh receptor Patched in both the adult rat hippocampus and neural progenitor cells isolated from this region. In addition, Shh elicited a strong, dose-dependent proliferative response in progenitors in vitro. Furthermore, adeno-associated viral vector delivery of shh cDNA to the hippocampus elicited a 3.3-fold increase in cell proliferation. Finally, the pharmacological inhibitor of Shh signaling cyclopamine reduced hippocampal neural progenitor proliferation in vivo. This work identifies Shh as a regulator of adult hippocampal neural stem cells.

Journal ArticleDOI
TL;DR: The gaze cascade effect was also present when participants compared abstract, unfamiliar shapes for attractiveness, suggesting that orienting and preference for objects in general are intrinsically linked in a positive feedback loop leading to the conscious choice.
Abstract: Emotions operate along the dimension of approach and aversion, and it is reasonable to assume that orienting behavior is intrinsically linked to emotionally involved processes such as preference decisions. Here we describe a gaze 'cascade effect' that was present when human observers were shown pairs of human faces and instructed to decide which face was more attractive. Their gaze was initially distributed evenly between the two stimuli, but then gradually shifted toward the face that they eventually chose. Gaze bias was significantly weaker in a face shape discrimination task. In a second series of experiments, manipulation of gaze duration, but not exposure duration alone, biased observers' preference decisions. We thus conclude that gaze is actively involved in preference formation. The gaze cascade effect was also present when participants compared abstract, unfamiliar shapes for attractiveness, suggesting that orienting and preference for objects in general are intrinsically linked in a positive feedback loop leading to the conscious choice.

Journal ArticleDOI
TL;DR: Differentiation along the glial lineage may be a default state of development reflected in the progression of stem cells along the neuroepithelial→radial glia→astrocyte lineage.
Abstract: Glia are the most numerous cells in the brain, and their many diverse functions highlight their essential role in the nervous system. Recent studies have revealed an unexpected new role for glia in a wide variety of species, that of stem cells/progenitors in the adult and embryonic brain. Differentiation along the glial lineage may be a default state of development reflected in the progression of stem cells along the neuroepithelial-->radial glia-->astrocyte lineage.

Journal ArticleDOI
TL;DR: In this paper, the authors showed that repeated cocaine treatment and withdrawal produces changes in brain function thought to be involved in relapse to drug use, and that withdrawal from repeated cocaine increases susceptibility to relapse in part by reducing cystine/glutamate exchange, and restoring exchanger activity prevents cocaine-primed drug seeking.
Abstract: Repeated cocaine treatment and withdrawal produces changes in brain function thought to be involved in relapse to drug use. Withdrawal from repeated cocaine reduced in vivo extracellular glutamate in the nucleus accumbens of rats by decreasing the exchange of extracellular cystine for intracellular glutamate. In vivo restoration of cystine/glutamate exchange by intracranial perfusion of cystine or systemically administered N-acetylcysteine normalized the levels of glutamate in cocaine-treated subjects. To determine if the reduction in nonvesicular glutamate release is a mediator of relapse, we examined cocaine-primed reinstatement of drug seeking after cocaine self-administration was stopped. Reinstatement was prevented by stimulating cystine/glutamate exchange with N-acetylcysteine and restoring extracellular glutamate. Thus, withdrawal from repeated cocaine increases susceptibility to relapse in part by reducing cystine/glutamate exchange, and restoring exchanger activity prevents cocaine-primed drug seeking.

Journal ArticleDOI
TL;DR: Results show that, for the purpose of odor quality discrimination, a fully refined olfactory sensory representation can emerge within a single sensorimotor or theta cycle, suggesting that each sniff can be considered a snapshot of the Olfactory world.
Abstract: The sense of smell is typically thought of as a 'slow' sense, but the true temporal constraints on the accuracy of olfactory perception are not known. It has been proposed that animals make finer odor discriminations at the expense of additional processing time. To test this idea, we measured the relationship between the speed and accuracy of olfactory discrimination in rats. We found that speed of discrimination was independent of odor similarity, as measured by overlap of glomerular activity patterns. Even when pushed to psychophysical limits using mixtures of two odors, rats needed to take only one sniff (<200 ms at theta frequency) to make a decision of maximum accuracy. These results show that, for the purpose of odor quality discrimination, a fully refined olfactory sensory representation can emerge within a single sensorimotor or theta cycle, suggesting that each sniff can be considered a snapshot of the olfactory world.

Journal ArticleDOI
TL;DR: In a human cognitive control task, it was found that it was not the stimulus-independent level of conflict that was responsible for the conflict-adaptation effect but rather an episodic memory phenomenon: stimulus-specific priming.
Abstract: According to the 'conflict-monitoring' model, a leading theory of cognitive control1,2,3,4, information-processing conflict registered in the anterior cingulate cortex (ACC) triggers the prefrontal cortex to reduce conflict susceptibility. Here we show that the existing empirical support for an online modulation of susceptibility to conflict through immediately preceding conflict, the 'conflict-adaptation effect'1,5, needs to be reevaluated. In a human cognitive control task, we found that it was not the stimulus-independent level of conflict that was responsible for the conflict-adaptation effect but rather an episodic memory phenomenon: stimulus-specific priming6.

Journal ArticleDOI
TL;DR: A functional architecture for music processing that captures the typical properties of modular organization is proposed, which rests essentially on the analysis of music-related deficits in neurologically impaired individuals but provides useful guidelines for exploring the music faculty in normal people, using methods such as neuroimaging.
Abstract: The music faculty is not a monolithic entity that a person either has or does not. Rather, it comprises a set of neurally isolable processing components, each having the potential to be specialized for music. Here we propose a functional architecture for music processing that captures the typical properties of modular organization. The model rests essentially on the analysis of music-related deficits in neurologically impaired individuals, but provides useful guidelines for exploring the music faculty in normal people, using methods such as neuroimaging.

Journal ArticleDOI
TL;DR: It is found that learning to read is associated with two patterns of change in brain activity: increased activity in left-hemisphere middle temporal and inferior frontal gyri and decreased activity in right inferotemporal cortical areas.
Abstract: The complexities of pediatric brain imaging have precluded studies that trace the neural development of cognitive skills acquired during childhood. Using a task that isolates reading-related brain activity and minimizes confounding performance effects, we carried out a cross-sectional functional magnetic resonance imaging (fMRI) study using subjects whose ages ranged from 6 to 22 years. We found that learning to read is associated with two patterns of change in brain activity: increased activity in left-hemisphere middle temporal and inferior frontal gyri and decreased activity in right inferotemporal cortical areas. Activity in the left-posterior superior temporal sulcus of the youngest readers was associated with the maturation of their phonological processing abilities. These findings inform current reading models and provide strong support for Orton's 1925 theory of reading development.

Journal ArticleDOI
TL;DR: It is found that basal synaptic input activates the NF-κB transcription factor by a pathway requiring the Ca2+/calmodulin-dependent kinase CaMKII and local submembranous Ca2+.
Abstract: Ca(2+)-regulated gene transcription is essential to diverse physiological processes, including the adaptive plasticity associated with learning. We found that basal synaptic input activates the NF-kappa B transcription factor by a pathway requiring the Ca(2+)/calmodulin-dependent kinase CaMKII and local submembranous Ca(2+) elevation. The p65:p50 NF-kappa B form is selectively localized at synapses; p65-deficient mice have no detectable synaptic NF-kappa B. Activated NF-kappa B moves to the nucleus and could directly transmute synaptic signals into altered gene expression. Mice lacking p65 show a selective learning deficit in the spatial version of the radial arm maze. These observations suggest that long-term changes to adult neuronal function caused by synaptic stimulation can be regulated by NF-kappa B nuclear translocation and gene activation.