Latest Articles Include:
- Ethical neuroscience
- Nature neuroscience 13(2):141 (2010)
Although institutional review boards are important ethical gatekeepers of human patient research, there is little data to evaluate their effectiveness. More coordination and a more transparent decision-making process is critical if review boards are to make appropriate and consistent decisions. - Renegade nuclear enzymes disrupt axonal integrity
- Nature neuroscience 13(2):143-144 (2010)
How does axonal loss, a hallmark of multiple sclerosis, occur? A study in this issue implicates histone deacetylase 1 (HDAC1), better known for regulating DNA transcription, in such axon degeneration. HDAC1 is exported from the nucleus and interacts with motor proteins, blocking axonal transport and leading to axon loss. - A silver lining to stroke: does ischemia generate new cortical interneurons?
- Nature neuroscience 13(2):145-146 (2010)
New work identifies a latent population of neuronal progenitor cells in neocortical layer 1 of adult rats. These cells proliferate in response to forebrain ischemia, then integrate into the cortical network as interneurons. - A 'sustain pedal' in the hippocampus?
- Nature neuroscience 13(2):146-148 (2010)
A study reveals that a largely ignored cell type in the dentate gyrus, semilunar granule cells, are persistently depolarized after a transient input and recruit interneurons to regulate the gating of information into the hippocampus. - Multisensory integration: an inner tongue puts an outer nose in context
- Nature neuroscience 13(2):148-149 (2010)
By demonstrating that inactivation of gustatory cortex influences olfactory recognition, a new study finds that the interaction between taste and smell is bidirectional. - Shining a spotlight on headaches
- Nature neuroscience 13(2):150-151 (2010)
Many headaches are worsened by light exposure. A new study uses a combination of human and rat experiments to suggest that a previously unknown retinal input to the thalamus may be important in such photophobia. - Amongst equals
- Nature neuroscience 13(2):151 (2010)
Personality differences among individuals can greatly influence how they divide resources. For example, some people are more averse to inequalities in resource provision than others. - Parallel pathways for vocal learning in basal ganglia of songbirds
Bottjer SW Altenau B - Nature neuroscience 13(2):153-155 (2010)
The cortical nucleus LMAN (lateral magnocellular nucleus of the anterior nidopallium) provides the output of a basal ganglia pathway that is necessary for vocal learning in juvenile songbirds. The shell subregion of LMAN (LMANshell) gives rise to recurrent loops that may subserve specific learning-related functions. We found that lesions in the LMANshell pathway caused no immediate disruption of vocal behavior, but prevented the development of stable vocal sequences and the ability to imitate vocal sounds. - The relationship between visual resolution and cone spacing in the human fovea
Rossi EA Roorda A - Nature neuroscience 13(2):156-157 (2010)
Visual resolution decreases rapidly outside of the foveal center. The anatomical and physiological basis for this reduction is unclear. We used simultaneous adaptive optics imaging and psychophysical testing to measure cone spacing and resolution across the fovea, and found that resolution was limited by cone spacing only at the foveal center. Immediately outside of the center, resolution was worse than cone spacing predicted and better matched the sampling limit of midget retinal ganglion cells. - State dependence of olfactory perception as a function of taste cortical inactivation
Fortis-Santiago Y Rodwin BA Neseliler S Piette CE Katz DB - Nature neuroscience 13(2):158-159 (2010)
As anyone who has suffered through a head cold knows, food eaten when the olfactory system is impaired tastes 'wrong', an experience that leads many to conclude that taste stimuli are processed normally only when the olfactory system is unimpaired. Evidence that the taste system influences olfactory perception, however, has been vanishingly rare. We found just such an influence; if taste cortex was inactivated when an odor was first presented, later presentations were properly appreciated only if taste cortex was again inactivated. - Activity in the amygdala elicited by unfair divisions predicts social value orientation
Haruno M Frith CD - Nature neuroscience 13(2):160-161 (2010)
'Social value orientation' characterizes individual differences in anchoring attitudes toward the division of resources. Here, by contrasting people with prosocial and individualistic orientations using functional magnetic resonance imaging, we demonstrate that degree of inequity aversion in prosocials is predictable from amygdala activity and unaffected by cognitive load. This result suggests that automatic emotional processing in the amygdala lies at the core of prosocial value orientation. - Tsc2-Rheb signaling regulates EphA-mediated axon guidance
- Nature neuroscience 13(2):163-172 (2010)
Tuberous sclerosis complex is a disease caused by mutations in the TSC1 or TSC2 genes, which encode a protein complex that inhibits mTOR kinase signaling by inactivating the Rheb GTPase. Activation of mTOR promotes the formation of benign tumors in various organs and the mechanisms underlying the neurological symptoms of the disease remain largely unknown. We found that Tsc2 haploinsufficiency in mice caused aberrant retinogeniculate projections that suggest defects in EphA receptor–dependent axon guidance. We also found that EphA receptor activation by ephrin-A ligands in neurons led to inhibition of extracellular signal–regulated kinase 1/2 (ERK1/2) activity and decreased inhibition of Tsc2 by ERK1/2. Thus, ephrin stimulation inactivates the mTOR pathway by enhancing Tsc2 activity. Furthermore, Tsc2 deficiency and hyperactive Rheb constitutively activated mTOR and inhibited ephrin-induced growth cone collapse. Our results indicate that TSC2-Rheb-mTOR signaling co! operates with the ephrin-Eph receptor system to control axon guidance in the visual system. - Ischemia-induced neurogenesis of neocortical layer 1 progenitor cells
Ohira K Furuta T Hioki H Nakamura KC Kuramoto E Tanaka Y Funatsu N Shimizu K Oishi T Hayashi M Miyakawa T Kaneko T Nakamura S - Nature neuroscience 13(2):173-179 (2010)
Adult mammalian neurogenesis occurs in the hippocampus and the olfactory bulb, whereas neocortical adult neurogenesis remains controversial. Several occurrences of neocortical adult neurogenesis in injured neocortex were recently reported, suggesting that neural stem cells (NSCs) or neuronal progenitor cells (NPCs) that can be activated by injury are maintained in the adult brain. However, it is not clear whether or where neocortical NSCs/NPCs exist in the brain. We found NPCs in the neocortical layer 1 of adult rats and observed that their proliferation was highly activated by global forebrain ischemia. Using retrovirus-mediated labeling of layer 1 proliferating cells with membrane-targeted green fluorescent protein, we found that the newly generated neurons were GABAergic and that the neurons were functionally integrated into the neuronal circuitry. Our results suggest that layer 1 NPCs are a source of adult neurogenesis under ischemic conditions. - HDAC1 nuclear export induced by pathological conditions is essential for the onset of axonal damage
Kim JY Shen S Dietz K He Y Howell O Reynolds R Casaccia P - Nature neuroscience 13(2):180-189 (2010)
Histone deacetylase 1 (HDAC1) is a nuclear enzyme involved in transcriptional repression. We detected cytosolic HDAC1 in damaged axons in brains of humans with multiple sclerosis and of mice with cuprizone-induced demyelination, in ex vivo models of demyelination and in cultured neurons exposed to glutamate and tumor necrosis factor-α. Nuclear export of HDAC1 was mediated by the interaction with the nuclear receptor CRM-1 and led to impaired mitochondrial transport. The formation of complexes between exported HDAC1 and members of the kinesin family of motor proteins hindered the interaction with cargo molecules, thereby inhibiting mitochondrial movement and inducing localized beading. This effect was prevented by inhibiting HDAC1 nuclear export with leptomycin B, treating neurons with pharmacological inhibitors of HDAC activity or silencing HDAC1 but not other HDAC isoforms. Together these data identify nuclear export of HDAC1 as a critical event for impaired mitochon! drial transport in damaged neurons. - Amyloid beta from axons and dendrites reduces local spine number and plasticity
Wei W Nguyen LN Kessels HW Hagiwara H Sisodia S Malinow R - Nature neuroscience 13(2):190-196 (2010)
Excessive synaptic loss is thought to be one of the earliest events in Alzheimer's disease. Amyloid beta (Aβ), a peptide secreted in an activity-modulated manner by neurons, has been implicated in the pathogenesis of Alzheimer's disease by removing dendritic spines, sites of excitatory synaptic transmission. However, issues regarding the subcellular source of Aβ, as well as the mechanisms of its production and actions that lead to synaptic loss, remain poorly understood. In rat organotypic slices, we found that acute overproduction of either axonal or dendritic Aβ reduced spine density and plasticity at nearby (~5–10 μm) dendrites. The production of Aβ and its effects on spines were sensitive to blockade of action potentials or nicotinic receptors; the effects of Aβ (but not its production) were sensitive to NMDA receptor blockade. Notably, only 30–60 min blockade of Aβ overproduction permitted induction of plasticity. Our results indicate that continuous ov! erproduction of Aβ at dendrites or axons acts locally to reduce the number and plasticity of synapses. - Synaptic activation of kainate receptors gates presynaptic CB1 signaling at GABAergic synapses
- Nature neuroscience 13(2):197-204 (2010)
Glutamate can control inhibitory synaptic transmission through activation of presynaptic kainate receptors. We found that glutamate released by train stimulation of Schaffer collaterals could lead to either short-term depression or short-term facilitation of inhibitory synaptic transmission in mouse CA1 pyramidal neurons, depending on the presence of cannabinoid type 1 (CB1) receptors on GABAergic afferents. The train-induced depression of inhibition (t-Di) required the mobilization of 2-arachidonoylglycerol through postsynaptic activation of metabotropic glutamate receptors and [Ca2+] rise. GluK1 (GluR5)-dependent depolarization of GABAergic terminals enabled t-Di by facilitating presynaptic CB1 signaling. Thus, concerted activation of presynaptic CB1 receptors and kainate receptors mediates short-term depression of inhibitory synaptic transmission. In contrast, in inhibitory connections expressing GluK1, but not CB1, receptors, train stimulation of Schaffer collatera! ls led to short-term facilitation. Thus, activation of kainate receptors by synaptically released glutamate gates presynaptic CB1 signaling, which in turn controls the direction of short-term heterosynaptic plasticity. - Control of hippocampal gamma oscillation frequency by tonic inhibition and excitation of interneurons
Mann EO Mody I - Nature neuroscience 13(2):205-212 (2010)
Gamma-frequency oscillations depend on phasic synaptic GABAA receptor (GABAAR)-mediated inhibition to synchronize spike timing. The spillover of synaptically released GABA can also activate extrasynaptic GABAARs, and such tonic inhibition may also contribute to modulating network dynamics. In many neuronal cell types, tonic inhibition is mediated by δ subunit–containing GABAARs. We found that the frequency of in vitro cholinergically induced gamma oscillations in the mouse hippocampal CA3 region was increased by the activation of NMDA receptors (NMDARs) on interneurons. The NMDAR-dependent increase of gamma oscillation frequency was counteracted by the tonic inhibition of the interneurons mediated by δ subunit–containing GABAARs. Recordings of synaptic currents during gamma activity revealed that NMDAR-mediated increases in oscillation frequency correlated with a progressive synchronization of phasic excitation and inhibition in the network. Thus, the balance bet! ween tonic excitation and tonic inhibition of interneurons may modulate gamma frequency by shaping interneuronal synchronization. - Representing information in cell assemblies: persistent activity mediated by semilunar granule cells
Larimer P Strowbridge BW - Nature neuroscience 13(2):213-222 (2010)
Here we found that perforant path stimulation in rat hippocampal slices evoked long-lasting barrages of synaptic inputs in subpopulations of dentate gyrus mossy cells and hilar interneurons. Synaptic barrages triggered persistent firing in hilar neurons (hilar up-states). We found that synaptic barrages originate from semilunar granule cells (SGCs), glutamatergic neurons in the inner molecular layer that generate long-duration plateau potentials in response to excitatory synaptic input. MK801, nimodipine and nickel all abolished both stimulus-evoked plateau potentials in SGCs and synaptic barrages in downstream hilar neurons without blocking fast synaptic transmission. Hilar up-states triggered functional inhibition in granule cells that persisted for more than 10 s. Hilar cell assemblies, identified by simultaneous triple and paired intracellular recordings, were linked by persistent firing in SGCs. Population responses recorded in hilar neurons accurately encoded sti! mulus identity. Stimulus-evoked up-states in the dentate gyrus represent a potential cellular basis for hippocampal working memory. - A single fear-inducing stimulus induces a transcription-dependent switch in synaptic AMPAR phenotype
Liu Y Formisano L Savtchouk I Takayasu Y Szabó G Zukin RS Liu SJ - Nature neuroscience 13(2):223-231 (2010)
Changes in emotional state are known to alter neuronal excitability and can modify learning and memory formation. Such experience-dependent neuronal plasticity can be long-lasting and is thought to involve the regulation of gene transcription. We found that a single fear-inducing stimulus increased GluR2 (also known as Gria2) mRNA abundance and promoted synaptic incorporation of GluR2-containing AMPA receptors (AMPARs) in mouse cerebellar stellate cells. The switch in synaptic AMPAR phenotype was mediated by noradrenaline and action potential prolongation. The subsequent rise in intracellular Ca2+ and activation of Ca2+-sensitive ERK/MAPK signaling triggered new GluR2 gene transcription and a switch in the synaptic AMPAR phenotype from GluR2-lacking, Ca2+-permeable receptors to GluR2-containing, Ca2+-impermeable receptors on the order of hours. The change in glutamate receptor phenotype altered synaptic efficacy in cerebellar stellate cells. Thus, a single fear-inducin! g stimulus can induce a long-term change in synaptic receptor phenotype and may alter the activity of an inhibitory neural network. - Glutamate co-release at GABA/glycinergic synapses is crucial for the refinement of an inhibitory map
- Nature neuroscience 13(2):232-238 (2010)
Many nonglutamatergic synaptic terminals in the mammalian brain contain the vesicular glutamate transporter 3 (VGLUT3), indicating that they co-release the excitatory neurotransmitter glutamate. However, the functional role of glutamate co-transmission at these synapses is poorly understood. In the auditory system, VGLUT3 expression and glutamate co-transmission are prominent in a developing GABA/glycinergic sound-localization pathway. We found that mice with a genetic deletion of Vglut3 (also known as Slc17a8) had disrupted glutamate co-transmission and severe impairment in the refinement of this inhibitory pathway. Specifically, loss of glutamate co-transmission disrupted synaptic silencing and the strengthening of GABA/glycinergic connections that normally occur with maturation. Functional mapping studies further revealed that these deficits markedly degraded the precision of tonotopy in this inhibitory auditory pathway. These results indicate that glutamate co-tran! smission is crucial for the synaptic reorganization and topographic specification of a developing inhibitory circuit. - A neural mechanism for exacerbation of headache by light
- Nature neuroscience 13(2):239-245 (2010)
The perception of migraine headache, which is mediated by nociceptive signals transmitted from the cranial dura mater to the brain, is uniquely exacerbated by exposure to light. We found that exacerbation of migraine headache by light is prevalent among blind individuals who maintain non–image-forming photoregulation in the face of massive rod/cone degeneration. Using single-unit recording and neural tract tracing in the rat, we identified dura-sensitive neurons in the posterior thalamus whose activity was distinctly modulated by light and whose axons projected extensively across layers I–V of somatosensory, visual and associative cortices. The cell bodies and dendrites of such dura/light-sensitive neurons were apposed by axons originating from retinal ganglion cells (RGCs), predominantly from intrinsically photosensitive RGCs, the principle conduit of non–image-forming photoregulation. We propose that photoregulation of migraine headache is exerted by a non–im! age-forming retinal pathway that modulates the activity of dura-sensitive thalamocortical neurons. - Activation of groups of excitatory neurons in the mammalian spinal cord or hindbrain evokes locomotion
- Nature neuroscience 13(2):246-252 (2010)
Central pattern generators (CPGs) are spinal neuronal networks required for locomotion. Glutamatergic neurons have been implicated as being important for intrinsic rhythm generation in the CPG and for the command signal for initiating locomotion, although this has not been demonstrated directly. We used a newly generated vesicular glutamate transporter 2–channelrhodopsin2–yellow fluorescent protein (Vglut2-ChR2-YFP) mouse to directly examine the functional role of glutamatergic neurons in rhythm generation and initiation of locomotion. This mouse line expressed ChR2-YFP in the spinal cord and hindbrain. ChR2-YFP was reliably expressed in Vglut2-positive cells and YFP-expressing cells could be activated by light. Photo-stimulation of either the lumbar spinal cord or the caudal hindbrain was sufficient to both initiate and maintain locomotor-like activity. Our results indicate that glutamatergic neurons in the spinal cord are critical for initiating or maintaining th! e rhythm and that activation of hindbrain areas containing the locomotor command regions is sufficient to directly activate the spinal locomotor network. - The descending corticocollicular pathway mediates learning-induced auditory plasticity
Bajo VM Nodal FR Moore DR King AJ - Nature neuroscience 13(2):253-260 (2010)
Descending projections from sensory areas of the cerebral cortex are among the largest pathways in the brain, suggesting that they are important for subcortical processing. Although corticofugal inputs have been shown to modulate neuronal responses in the thalamus and midbrain, the behavioral importance of these changes remains unknown. In the auditory system, one of the major descending pathways is from cortical layer V pyramidal cells to the inferior colliculus in the midbrain. We examined the role of these neurons in experience-dependent recalibration of sound localization in adult ferrets by selectively killing the neurons using chromophore-targeted laser photolysis. When provided with appropriate training, animals normally relearn to localize sound accurately after altering the spatial cues available by reversibly occluding one ear. However, this ability was lost after eliminating corticocollicular neurons, whereas normal sound-localization accuracy was unaffected! . The integrity of this descending pathway is therefore critical for learning-induced localization plasticity. - Inactivation of primate superior colliculus impairs covert selection of signals for perceptual judgments
Lovejoy LP Krauzlis RJ - Nature neuroscience 13(2):261-266 (2010)
Primates base perceptual judgments on some sensory inputs while ignoring others. The covert selection of sensory information for perception is often thought to be accomplished mostly by the cerebral cortex, whereas the overt orienting toward relevant stimuli involves various additional structures such as the superior colliculus, a subcortical region involved in the control of eye movements. Contrary to this view, we show that the superior colliculus is necessary for determining which stimuli will inform perceptual judgments, even in the absence of orienting movements. Reversible inactivation of the superior colliculus in monkeys performing a motion discrimination task caused profound inattention for stimuli in the affected visual field, but only when distracters containing counterinformative signals appeared in the unaffected field. When distracting stimuli contained no information, discrimination performance was largely unaffected. Thus, the superior colliculus is a b! ottleneck in the covert selection of signals for perceptual judgments.
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