Showing papers in "Nature Neuroscience in 2008"
TL;DR: It is found that the outcome of a decision can be encoded in brain activity of prefrontal and parietal cortex up to 10 s before it enters awareness.
Abstract: There has been a long controversy as to whether subjectively 'free' decisions are determined by brain activity ahead of time. We found that the outcome of a decision can be encoded in brain activity of prefrontal and parietal cortex up to 10 s before it enters awareness. This delay presumably reflects the operation of a network of high-level control areas that begin to prepare an upcoming decision long before it enters awareness.
1,311 citations
TL;DR: These findings demonstrate that mutant astrocytes are viable targets for therapies for slowing the progression of non–cell autonomous killing of motor neurons in ALS.
Abstract: Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis
1,054 citations
TL;DR: It is suggested that continuous neurogenesis is required for the maintenance and reorganization of the whole interneuron system in the olfactory bulb, the modulation and refinement of the existing neuronal circuits in the dentate gyrus and the normal behaviors involved in hippocampal-dependent memory.
Abstract: Neurogenesis occurs continuously in the forebrain of adult mammals, but the functional importance of adult neurogenesis is still unclear. Here, using a genetic labeling method in adult mice, we found that continuous neurogenesis results in the replacement of the majority of granule neurons in the olfactory bulb and a substantial addition of granule neurons to the hippocampal dentate gyrus. Genetic ablation of newly formed neurons in adult mice led to a gradual decrease in the number of granule cells in the olfactory bulb, inhibition of increases in the granule cell number in the dentate gyrus and impairment of behaviors in contextual and spatial memory, which are known to depend on hippocampus. These results suggest that continuous neurogenesis is required for the maintenance and reorganization of the whole interneuron system in the olfactory bulb, the modulation and refinement of the existing neuronal circuits in the dentate gyrus and the normal behaviors involved in hippocampal-dependent memory.
994 citations
TL;DR: Findings reveal a mechanism by which frontal and basal ganglia activity exerts attentional control over access to working memory storage in the parietal cortex in humans, and makes an important contribution to inter-individual differences in working memory capacity.
Abstract: Our capacity to store information in working memory might be determined by the degree to which only relevant information is remembered. The question remains as to how this selection of relevant items to be remembered is accomplished. Here we show that activity in the prefrontal cortex and basal ganglia preceded the filtering of irrelevant information and that activity, particularly in the globus pallidus, predicted the extent to which only relevant information is stored. The preceding frontal and basal ganglia activity were also associated with inter-individual differences in working memory capacity. These findings reveal a mechanism by which frontal and basal ganglia activity exerts attentional control over access to working memory storage in the parietal cortex in humans, and makes an important contribution to inter-individual differences in working memory capacity.
964 citations
TL;DR: Results suggest that achieving excellence in sports may be related to the fine-tuning of specific anticipatory 'resonance' mechanisms that endow elite athletes' brains with the ability to predict others' actions ahead of their realization.
Abstract: We combined psychophysical and transcranial magnetic stimulation studies to investigate the dynamics of action anticipation and its underlying neural correlates in professional basketball players. Athletes predicted the success of free shots at a basket earlier and more accurately than did individuals with comparable visual experience (coaches or sports journalists) and novices. Moreover, performance between athletes and the other groups differed before the ball was seen to leave the model's hands, suggesting that athletes predicted the basket shot's fate by reading the body kinematics. Both visuo-motor and visual experts showed a selective increase of motor-evoked potentials during observation of basket shots. However, only athletes showed a time-specific motor activation during observation of erroneous basket throws. Results suggest that achieving excellence in sports may be related to the fine-tuning of specific anticipatory 'resonance' mechanisms that endow elite athletes' brains with the ability to predict others' actions ahead of their realization.
859 citations
TL;DR: The fates of adult OLPs are followed in Pdgfra-creERT2/Rosa26-YFP double-transgenic mice and it is found that they generated many myelinating oligodendrocytes during adulthood, but there is no evidence for astrocyte production in gray or white matter.
Abstract: About 4% of the cells in the adult rodent brain are PDGFRA+ NG2+ glia, derived from the oligodendrocyte lineage. Rivers and colleagues constructed a transgenic mouse to fate map the PDGFRA+ glia. In the adult corpus callosum, these cells generated substantial numbers of late-myelinating oligodendrocytes. In the cortex, little late myelination was observed; instead, PDGFRA+ precursors seemed to continuously generate small numbers of projection neurons mainly in piriform cortex.
832 citations
TL;DR: Reinforcement learning models that focus on the striatum and dopamine can predict the choices of animals and people but representation of reward expectation and of reward prediction errors that are pertinent to decision making are not confined to these regions but are also found in prefrontal and cingulate cortex.
Abstract: Reinforcement learning models that focus on the striatum and dopamine can predict the choices of animals and people. Representations of reward expectation and of reward prediction errors that are pertinent to decision making, however, are not confined to these regions but are also found in prefrontal and cingulate cortex. Moreover, decisions are not guided solely by the magnitude of the reward that is expected. Uncertainty in the estimate of the reward expectation, the value of information that might be gained by taking a course of action and the cost of an action all influence the manner in which decisions are made through prefrontal and cingulate cortex.
817 citations
TL;DR: Compared cortical connectivity in humans, chimpanzees and macaques and found a prominent temporal lobe projection of the human arcuate fasciculus that is much smaller or absent in nonhuman primates, which may be relevant to the evolution of language.
Abstract: The arcuate fasciculus is a white-matter fiber tract that is involved in human language. Here we compared cortical connectivity in humans, chimpanzees and macaques (Macaca mulatta) and found a prominent temporal lobe projection of the human arcuate fasciculus that is much smaller or absent in nonhuman primates. This human specialization may be relevant to the evolution of language.
755 citations
TL;DR: It is shown that, in rat cortex and hippocampus, GluR1-containing AMPA receptor levels are high during wakefulness and low during sleep, and changes in the phosphorylation states of AMPARs, CamKII and GSK3β are consistent with synaptic potentiation during wakeful and depression during sleep.
Abstract: Plastic changes occurring during wakefulness aid in the acquisition and consolidation of memories. For some memories, further consolidation requires sleep, but whether plastic processes during wakefulness and sleep differ is unclear. We show that, in rat cortex and hippocampus, GluR1-containing AMPA receptor (AMPAR) levels are high during wakefulness and low during sleep, and changes in the phosphorylation states of AMPARs, CamKII and GSK3beta are consistent with synaptic potentiation during wakefulness and depression during sleep. Furthermore, slope and amplitude of cortical evoked responses increase after wakefulness, decrease after sleep and correlate with changes in slow-wave activity, a marker of sleep pressure. Changes in molecular and electrophysiological indicators of synaptic strength are largely independent of the time of day. Finally, cortical long-term potentiation can be easily induced after sleep, but not after wakefulness. Thus, wakefulness appears to be associated with net synaptic potentiation, whereas sleep may favor global synaptic depression, thereby preserving an overall balance of synaptic strength.
743 citations
TL;DR: This work analyzed gene coexpression relationships in microarray data generated from specific human brain regions and identified modules of coexpressed genes that correspond to neurons, oligodendrocytes, astroCytes and microglia, providing an initial description of the transcriptional programs that distinguish the major cell classes of the human brain.
Abstract: The enormous complexity of the human brain ultimately derives from a finite set of molecular instructions encoded in the human genome. These instructions can be directly studied by exploring the organization of the brain's transcriptome through systematic analysis of gene coexpression relationships. We analyzed gene coexpression relationships in microarray data generated from specific human brain regions and identified modules of coexpressed genes that correspond to neurons, oligodendrocytes, astrocytes and microglia. These modules provide an initial description of the transcriptional programs that distinguish the major cell classes of the human brain and indicate that cell type-specific information can be obtained from whole brain tissue without isolating homogeneous populations of cells. Other modules corresponded to additional cell types, organelles, synaptic function, gender differences and the subventricular neurogenic niche. We found that subventricular zone astrocytes, which are thought to function as neural stem cells in adults, have a distinct gene expression pattern relative to protoplasmic astrocytes. Our findings provide a new foundation for neurogenetic inquiries by revealing a robust and previously unrecognized organization to the human brain transcriptome.
726 citations
TL;DR: Structural and functional evidence indicates that axons of adult-born granule cells establish synapses with hilar interneurons, mossy cells and CA3 pyramidal cells and release glutamate as their main neurotransmitter.
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. By combining retroviral expression of green fluorescent protein in adult-born neurons of the mouse dentate gyrus with immuno-electron microscopy, we found output synapses that were formed by labeled terminals on appropriate target cells in the CA3 area and the hilus. Furthermore, retroviral expression of channelrhodopsin-2 allowed us to light-stimulate newborn granule cells and identify postsynaptic target neurons by whole-cell recordings in acute slices. Our structural and functional evidence indicates that axons of adult-born granule cells establish synapses with hilar interneurons, mossy cells and CA3 pyramidal cells and release glutamate as their main neurotransmitter.
TL;DR: Using simultaneous intracellular recordings in pairs of nearby neurons in vivo, it is found that excitatory and inhibitory inputs are continuously synchronized and correlated in strength during spontaneous and sensory-evoked activities in the rat somatosensory cortex.
Abstract: Temporal and quantitative relations between excitatory and inhibitory inputs in the cortex are central to its activity, yet they remain poorly understood. In particular, a controversy exists regarding the extent of correlation between cortical excitation and inhibition. Using simultaneous intracellular recordings in pairs of nearby neurons in vivo, we found that excitatory and inhibitory inputs are continuously synchronized and correlated in strength during spontaneous and sensory-evoked activities in the rat somatosensory cortex.
TL;DR: This work measured behavioral and physiological responses of monkeys on a two- and four-choice direction-discrimination decision task and observed a time-dependent rise in firing rates that may impose a deadline for deciding.
Abstract: Simple perceptual tasks have laid the groundwork for understanding the neurobiology of decision-making. Here, we examined this foundation to explain how decision-making circuitry adjusts in the face of a more difficult task. We measured behavioral and physiological responses of monkeys on a two- and four-choice direction-discrimination decision task. For both tasks, firing rates in the lateral intraparietal area appeared to reflect the accumulation of evidence for or against each choice. Evidence accumulation began at a lower firing rate for the four-choice task, but reached a common level by the end of the decision process. The larger excursion suggests that the subjects required more evidence before making a choice. Furthermore, on both tasks, we observed a time-dependent rise in firing rates that may impose a deadline for deciding. These physiological observations constitute an effective strategy for handling increased task difficulty. The differences appear to explain subjects' accuracy and reaction times.
TL;DR: By manipulating the likelihood of stimulus repetition, this work found that repetition suppression in the human brain was reduced when stimulus repetitions were improbable (and thus, unexpected), suggesting a relative reduction in top-down perceptual 'prediction error' when processing an expected, compared with an unexpected, stimulus.
Abstract: Stimulus-evoked neural activity is attenuated on stimulus repetition (repetition suppression), a phenomenon that is attributed to largely automatic processes in sensory neurons By manipulating the likelihood of stimulus repetition, we found that repetition suppression in the human brain was reduced when stimulus repetitions were improbable (and thus, unexpected) Our data suggest that repetition suppression reflects a relative reduction in top-down perceptual 'prediction error' when processing an expected, compared with an unexpected, stimulus
TL;DR: This work looked for the signature of short-term plasticity in the fine-timescale spiking relationships of a simultaneously recorded population of physiologically identified pyramidal cells and interneurons, in the medial prefrontal cortex of the rat, in a working memory task and found evidence for both firing pattern–dependent facilitation and depression.
Abstract: Although short-term plasticity is believed to play a fundamental role in cortical computation, empirical evidence bearing on its role during behavior is scarce. Here we looked for the signature of short-term plasticity in the fine-timescale spiking relationships of a simultaneously recorded population of physiologically identified pyramidal cells and interneurons, in the medial prefrontal cortex of the rat, in a working memory task. On broader timescales, sequentially organized and transiently active neurons reliably differentiated between different trajectories of the rat in the maze. On finer timescales, putative monosynaptic interactions reflected short-term plasticity in their dynamic and predictable modulation across various aspects of the task, beyond a statistical accounting for the effect of the neurons' co-varying firing rates. Seeking potential mechanisms for such effects, we found evidence for both firing pattern-dependent facilitation and depression, as well as for a supralinear effect of presynaptic coincidence on the firing of postsynaptic targets.
TL;DR: Data obtained by antibody staining, whole-cell voltage-clamp and Na+ imaging, together with modeling, indicate that the Na+ channel density at the AIS of cortical pyramidal neurons is ∼50 times that in the proximal dendrites.
Abstract: The axon initial segment (AIS) is a specialized region in neurons where action potentials are initiated. It is commonly assumed that this process requires a high density of voltage-gated sodium (Na(+)) channels. Paradoxically, the results of patch-clamp studies suggest that the Na(+) channel density at the AIS is similar to that at the soma and proximal dendrites. Here we provide data obtained by antibody staining, whole-cell voltage-clamp and Na(+) imaging, together with modeling, which indicate that the Na(+) channel density at the AIS of cortical pyramidal neurons is approximately 50 times that in the proximal dendrites. Anchoring of Na(+) channels to the cytoskeleton can explain this discrepancy, as disruption of the actin cytoskeleton increased the Na(+) current measured in patches from the AIS. Computational models required a high Na(+) channel density (approximately 2,500 pS microm(-2)) at the AIS to account for observations on action potential generation and backpropagation. In conclusion, action potential generation requires a high Na(+) channel density at the AIS, which is maintained by tight anchoring to the actin cytoskeleton.
TL;DR: This article aims to sort out factors that affect the process of decision making from the viewpoint of reinforcement learning theory and to bridge between such computational needs and their neurophysiological substrates.
Abstract: Human and animal decisions are modulated by a variety of environmental and intrinsic contexts. Here I consider computational factors that can affect decision making and review anatomical structures and neurochemical systems that are related to contextual modulation of decision making. Expectation of a high reward can motivate a subject to go for an action despite a large cost, a decision that is influenced by dopamine in the anterior cingulate cortex. Uncertainty of action outcomes can promote risk taking and exploratory choices, in which norepinephrine and the orbitofrontal cortex appear to be involved. Predictable environments should facilitate consideration of longer-delayed rewards, which depends on serotonin in the dorsal striatum and dorsal prefrontal cortex. This article aims to sort out factors that affect the process of decision making from the viewpoint of reinforcement learning theory and to bridge between such computational needs and their neurophysiological substrates.
TL;DR: The explosion of studies on crowding is reviewed—in grating discrimination, letter and face recognition, visual search, selective attention, and reading—and a universal principle, the Bouma law is found, which is equal for all objects, although the effect is weaker between dissimilar objects.
Abstract: It is now emerging that vision is usually limited by object spacing rather than size. The visual system recognizes an object by detecting and then combining its features. ‘Crowding’ occurs when objects are too close together and features from several objects are combined into a jumbled percept. Here, we review the explosion of studies on crowding—in grating discrimination, letter and face recognition, visual search, selective attention, and reading—and find a universal principle, the Bouma law. The critical spacing required to prevent crowding is equal for all objects, although the effect is weaker between dissimilar objects. Furthermore, critical spacing at the cortex is independent of object position, and critical spacing at the visual field is proportional to object distance from fixation. The region where object spacing exceeds critical spacing is the ‘uncrowded window’. Observers cannot recognize objects outside of this window and its size limits the speed of reading and search. Object recognition means calling a chair a chair, despite variations in style, viewpoint, rendering and surrounding clutter. Crowding is a breakdown of object recognition. Let us begin by sketching a popular two-step model of object recognition: feature detection and combination. Features are components of images that are detected independently 1–4 . They are typically simple and nonoverlapping. The first step in object recognition is feature detection 4 . Each neuron in the primary visual cortex responds when a feature matches its receptive field. Only the features that drive neurons hard enough are detected 5 . In the second step, the brain combines some of the detected features to recognize the object. This combining step (including ‘integration’, ‘binding’, ‘segmentation’, ‘pooling’, ‘grouping’, ‘contour integration’ and ‘selective attention’) is still mysterious 3,4,6–11 .
TL;DR: It is found that single rat neocortical pyramidal neurons adapt with a time scale that depends on the time scale of changes in stimulus statistics, which is consistent with fractional order differentiation.
Abstract: Neural systems adapt to changes in stimulus statistics. The authors find that neocortical pyramidal neurons adapt with a time scale that depends on the time scale of changes in stimulus statistics, and that for individual neurons the firing is a fractional derivative of slowly varying stimulus parameters. Neural systems adapt to changes in stimulus statistics. However, it is not known how stimuli with complex temporal dynamics drive the dynamics of adaptation and the resulting firing rate. For single neurons, it has often been assumed that adaptation has a single time scale. We found that single rat neocortical pyramidal neurons adapt with a time scale that depends on the time scale of changes in stimulus statistics. This multiple time scale adaptation is consistent with fractional order differentiation, such that the neuron's firing rate is a fractional derivative of slowly varying stimulus parameters. Biophysically, even though neuronal fractional differentiation effectively yields adaptation with many time scales, we found that its implementation required only a few properly balanced known adaptive mechanisms. Fractional differentiation provides single neurons with a fundamental and general computation that can contribute to efficient information processing, stimulus anticipation and frequency-independent phase shifts of oscillatory neuronal firing.
TL;DR: These mice with an AgRP neuron–specific deletion of vesicular GABA transporter are lean, resistant to obesity and have an attenuated hyperphagic response to ghrelin, indicating that GABA release from AgRP neurons is important in regulating energy balance.
Abstract: The physiologic importance of GABAergic neurotransmission in hypothalamic neurocircuits is unknown. To examine the importance of GABA release from agouti-related protein (AgRP) neurons (which also release AgRP and neuropeptide Y), we generated mice with an AgRP neuron-specific deletion of vesicular GABA transporter. These mice are lean, resistant to obesity and have an attenuated hyperphagic response to ghrelin. Thus, GABA release from AgRP neurons is important in regulating energy balance.
TL;DR: A cation-conducting channelrhodopsin (VChR1) from Volvox carteri that can drive spiking at 589 nm, with excitation maximum red-shifted ∼70 nm compared with ChR2 is described, thereby defining a functionally distinct third category of microbial rhodopin proteins.
Abstract: The introduction of two microbial opsin-based tools, channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR), to neuroscience has generated interest in fast, multimodal, cell type-specific neural circuit control. Here we describe a cation-conducting channelrhodopsin (VChR1) from Volvox carteri that can drive spiking at 589 nm, with excitation maximum red-shifted approximately 70 nm compared with ChR2. These results demonstrate fast photostimulation with yellow light, thereby defining a functionally distinct third category of microbial rhodopsin proteins.
TL;DR: It is found that increasing ghrelin levels, through subcutaneous injections or calorie restriction, produced anxiolytic- and antidepressant-like responses in the elevated plus maze and forced swim test, demonstrating a previously unknown function for ghrel in defending against depressive-like symptoms of chronic stress.
Abstract: The peptide hormone ghrelin has previously been linked to the regulation of metabolism. This study in mice finds that increasing levels of ghrelin, either through subcutaneous injections or calorie restriction, has an anxiolytic and antidepressive effect. This reveals a previously unknown function for ghrelin. We found that increasing ghrelin levels, through subcutaneous injections or calorie restriction, produced anxiolytic- and antidepressant-like responses in the elevated plus maze and forced swim test. Moreover, chronic social defeat stress, a rodent model of depression, persistently increased ghrelin levels, whereas growth hormone secretagogue receptor (Ghsr) null mice showed increased deleterious effects of chronic defeat. Together, these findings demonstrate a previously unknown function for ghrelin in defending against depressive-like symptoms of chronic stress.
TL;DR: It is demonstrated that, in both insulin-deficient rats and insulin-resistant mice, diabetes impairs hippocampus-dependent memory, perforant path synaptic plasticity and adult neurogenesis, and the adrenal steroid corticosterone contributes to these adverse effects.
Abstract: Many organ systems are adversely affected by diabetes, including the brain, which undergoes changes that may increase the risk of cognitive decline. Although diabetes influences the hypothalamic-pituitary-adrenal axis, the role of this neuroendocrine system in diabetes-induced cognitive dysfunction remains unexplored. Here we demonstrate that, in both insulin-deficient rats and insulin-resistant mice, diabetes impairs hippocampus-dependent memory, perforant path synaptic plasticity and adult neurogenesis, and the adrenal steroid corticosterone contributes to these adverse effects. Rats treated with streptozocin have reduced insulin and show hyperglycemia, increased corticosterone, and impairments in hippocampal neurogenesis, synaptic plasticity and learning. Similar deficits are observed in db/db mice, which are characterized by insulin resistance, elevated corticosterone and obesity. Changes in hippocampal plasticity and function in both models are reversed when normal physiological levels of corticosterone are maintained, suggesting that cognitive impairment in diabetes may result from glucocorticoid-mediated deficits in neurogenesis and synaptic plasticity.
TL;DR: To restore photosensitivity, a light-activated cation channel is genetically targeted to second-order neurons of degenerated retinas in vivo in the Pde6brd1 mouse model, and ON bipolar cells that were engineered to be photosensitive induced light-evoked spiking activity in ganglion cells.
Abstract: Genetically encoded optical neuromodulators create an opportunity for circuit-specific intervention in neurological diseases. One of the diseases most amenable to this approach is retinal degeneration, where the loss of photoreceptors leads to complete blindness. To restore photosensitivity, we genetically targeted a light-activated cation channel, channelrhodopsin-2, to second-order neurons, ON bipolar cells, of degenerated retinas in vivo in the Pde6brd1 (also known as rd1) mouse model. In the absence of 'classical' photoreceptors, we found that ON bipolar cells that were engineered to be photosensitive induced light-evoked spiking activity in ganglion cells. The rescue of light sensitivity was selective to the ON circuits that would naturally respond to increases in brightness. Despite degeneration of the outer retina, our intervention restored transient responses and center-surround organization of ganglion cells. The resulting signals were relayed to the visual cortex and were sufficient for the animals to successfully perform optomotor behavioral tasks.
TL;DR: It is concluded that Shh signaling, acting through the primary cilia, has a critical role in the expansion and establishment of postnatal hippocampal progenitors.
Abstract: Neural stem cells that continue to produce neurons are retained in the adult hippocampal dentate gyrus. The mechanisms by which embryonic neural progenitors expand and transform into postnatal neural stem cells, an essential process for the continual production of neurons throughout life, remain unknown. We found that radial astrocytes, the postnatal progenitors in the dentate gyrus, failed to develop after embryonic ablation of ciliary genes or Smoothened (Smo), an essential component for Sonic hedgehog (Shh) signaling. Postnatal dentate neurogenesis failed in these mutant mice, and the dentate gyrus became severely hypotrophic. In contrast, expression of a constitutively active Smo (SmoM2-YFP) resulted in a marked expansion of the dentate gyrus. Double-mutant analyses suggested that both wild-type Smo and SmoM2-YFP function through the primary cilia. We conclude that Shh signaling, acting through the primary cilia, has a critical role in the expansion and establishment of postnatal hippocampal progenitors.
TL;DR: The findings show that perceptual cue integration occurs in nonhuman primates and identify a population of neurons that may form its neural basis.
Abstract: Human observers combine multiple sensory cues synergistically to achieve greater perceptual sensitivity, but little is known about the underlying neuronal mechanisms. We recorded the activity of neurons in the dorsal medial superior temporal (MSTd) area during a task in which trained monkeys combined visual and vestibular cues near-optimally to discriminate heading. During bimodal stimulation, MSTd neurons combined visual and vestibular inputs linearly with subadditive weights. Neurons with congruent heading preferences for visual and vestibular stimuli showed improvements in sensitivity that parallel behavioral effects. In contrast, neurons with opposite preferences showed diminished sensitivity under cue combination. Responses of congruent cells were more strongly correlated with monkeys' perceptual decisions than were responses of opposite cells, suggesting that the monkey monitored the activity of congruent cells to a greater extent during cue integration. These findings show that perceptual cue integration occurs in nonhuman primates and identify a population of neurons that may form its neural basis.
TL;DR: Perceptual learning does not appear to involve improvements in how sensory information is represented in the brain, but rather how the sensory representation is interpreted to form the decision that guides behavior.
Abstract: This study aimed to identify neural mechanisms that underlie perceptual learning in a visual-discrimination task. We trained two monkeys (Macaca mulatta) to determine the direction of visual motion while we recorded from their middle temporal area (MT), which in trained monkeys represents motion information that is used to solve the task, and lateral intraparietal area (LIP), which represents the transformation of motion information into a saccadic choice. During training, improved behavioral sensitivity to weak motion signals was accompanied by changes in motion-driven responses of neurons in LIP, but not in MT. The time course and magnitude of the changes in LIP correlated with the changes in behavioral sensitivity throughout training. Thus, for this task, perceptual learning does not appear to involve improvements in how sensory information is represented in the brain, but rather how the sensory representation is interpreted to form the decision that guides behavior.
TL;DR: Understanding decision making—indeed, understanding behavior itself—requires knowing how the brain responds to and uses information about uncertainty, particularly when describing a decision as 'risky'.
Abstract: Many decisions involve uncertainty, or imperfect knowledge about how choices lead to outcomes. Colloquial notions of uncertainty, particularly when describing a decision as 'risky', often carry connotations of potential danger as well. Gambling on a long shot, whether a horse at the racetrack or a foreign oil company in a hedge fund, can have negative consequences, but the impact of uncertainty on decision making extends beyond gambling. Indeed, uncertainty in some form pervades nearly all our choices in daily life. Stepping into traffic to hail a cab, braving an ice storm to be the first at work, or dating the boss's son or daughter also offer potentially great windfalls, at the expense of surety. We continually face trade-offs between options that promise safety and others that offer an uncertain potential for jackpot or bust. When mechanisms for dealing with uncertain outcomes fail, as in mental disorders such as problem gambling or addiction, the results can be disastrous. Thus, understanding decision making—indeed, understanding behavior itself—requires knowing how the brain responds to and uses information about uncertainty.
TL;DR: It is found that in rat neurons, synaptic activity, acting via NMDA receptor (NMDAR) signaling, boosted antioxidant defenses by making changes to the thioredoxin-peroxiredoxin system by influencing the progression of pathological processes associated with oxidative damage.
Abstract: Intrinsic antioxidant defenses are important for neuronal longevity. We found that in rat neurons, synaptic activity, acting via NMDA receptor (NMDAR) signaling, boosted antioxidant defenses by making changes to the thioredoxin-peroxiredoxin (Prx) system. Synaptic activity enhanced thioredoxin activity, facilitated the reduction of overoxidized Prxs and promoted resistance to oxidative stress. Resistance was mediated by coordinated transcriptional changes; synaptic NMDAR activity inactivated a previously unknown Forkhead box O target gene, the thioredoxin inhibitor Txnip. Conversely, NMDAR blockade upregulated Txnip in vivo and in vitro, where it bound thioredoxin and promoted vulnerability to oxidative damage. Synaptic activity also upregulated the Prx reactivating genes Sesn2 (sestrin 2) and Srxn1 (sulfiredoxin), via C/EBPβ and AP-1, respectively. Mimicking these expression changes was sufficient to strengthen antioxidant defenses. Trans-synaptic stimulation of synaptic NMDARs was crucial for boosting antioxidant defenses; chronic bath activation of all (synaptic and extrasynaptic) NMDARs induced no antioxidative effects. Thus, synaptic NMDAR activity may influence the progression of pathological processes associated with oxidative damage.
TL;DR: Slow spontaneous modulations in firing rate and gamma LFP as the likely correlates of spontaneous fMRI fluctuations in the human sensory cortex are pointed to.
Abstract: Animal studies have shown robust electrophysiological activity in the sensory cortex in the absence of stimuli or tasks. Similarly, recent human functional magnetic resonance imaging (fMRI) revealed widespread, spontaneously emerging cortical fluctuations. However, it is unknown what neuronal dynamics underlie this spontaneous activity in the human brain. Here we studied this issue by combining bilateral single-unit, local field potentials (LFPs) and intracranial electrocorticography (ECoG) recordings in individuals undergoing clinical monitoring. We found slow (<0.1 Hz, following 1/f-like profiles) spontaneous fluctuations of neuronal activity with significant interhemispheric correlations. These fluctuations were evident mainly in neuronal firing rates and in gamma (40-100 Hz) LFP power modulations. Notably, the interhemispheric correlations were enhanced during rapid eye movement and stage 2 sleep. Multiple intracranial ECoG recordings revealed clear selectivity for functional networks in the spontaneous gamma LFP power modulations. Our results point to slow spontaneous modulations in firing rate and gamma LFP as the likely correlates of spontaneous fMRI fluctuations in the human sensory cortex.