| 1. |
- Beets, Isabel, et al.
(författare)
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Natural Variation in a Dendritic Scaffold Protein Remodels Experience-Dependent Plasticity by Altering Neuropeptide Expression
- 2020
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Ingår i: Neuron. - : Elsevier. - 0896-6273 .- 1097-4199. ; 105:1, s. 106-121
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Tidskriftsartikel (refereegranskat)abstract
- The extent to which behavior is shaped by experience varies between individuals. Genetic differences contribute to this variation, but the neural mechanisms are not understood. Here, we dissect natural variation in the behavioral flexibility of two Caenorhabditis elegans wild strains. In one strain, a memory of exposure to 21% O2 suppresses CO2-evoked locomotory arousal; in the other, CO2 evokes arousal regardless of previous O2 experience. We map that variation to a polymorphic dendritic scaffold protein, ARCP-1, expressed in sensory neurons. ARCP-1 binds the Ca2+-dependent phosphodiesterase PDE-1 and co-localizes PDE-1 with molecular sensors for CO2 at dendritic ends. Reducing ARCP-1 or PDE-1 activity promotes CO2 escape by altering neuropeptide expression in the BAG CO2 sensors. Variation in ARCP-1 alters behavioral plasticity in multiple paradigms. Our findings are reminiscent of genetic accommodation, an evolutionary process by which phenotypic flexibility in response to environmental variation is reset by genetic change.
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| 2. |
- Eriksson, Johan, et al.
(författare)
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Neurocognitive Architecture of Working Memory
- 2015
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Ingår i: Neuron. - : CELL PRESS. - 0896-6273 .- 1097-4199. ; 88:1, s. 33-46
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Forskningsöversikt (refereegranskat)abstract
- A crucial role for working memory in temporary information processing and guidance of complex behavior has been recognized for many decades. There is emerging consensus that working-memory maintenance results from the interactions among long-term memory representations and basic processes, including attention, that are instantiated as reentrant loops between frontal and posterior cortical areas, as well as sub-cortical structures. The nature of such interactions can account for capacity limitations, lifespan changes, and restricted transfer after working-memory training. Recent data and models indicate that working memory may also be based on synaptic plasticity and that working memory can operate on non-consciously perceived information.
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| 3. |
- Iurilli, Giuliano, et al.
(författare)
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Sound-Driven Synaptic Inhibition in Primary Visual Cortex
- 2012
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Ingår i: Neuron. - : Elsevier BV. - 0896-6273 .- 1097-4199. ; 73:4, s. 814-28
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Tidskriftsartikel (refereegranskat)abstract
- Multimodal objects and events activate many sensory cortical areas simultaneously. This is possibly reflected in reciprocal modulations of neuronal activity, even at the level of primary cortical areas. However, the synaptic character of these interareal interactions, and their impact on synaptic and behavioral sensory responses are unclear. Here, we found that activation of auditory cortex by a noise burst drove local GABAergic inhibition on supragranular pyramids of the mouse primary visual cortex, via cortico-cortical connections. This inhibition was generated by sound-driven excitation of a limited number of cells in infragranular visual cortical neurons. Consequently, visually driven synaptic and spike responses were reduced upon bimodal stimulation. Also, acoustic stimulation suppressed conditioned behavioral responses to a dim flash, an effect that was prevented by acute blockade of GABAergic transmission in visual cortex. Thus, auditory cortex activation by salient stimuli degrades potentially distracting sensory processing in visual cortex by recruiting local, translaminar, inhibitory circuits.
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| 4. |
- Liu, Jian, et al.
(författare)
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Toxicity of familial ALS-linked SOD1 mutants from selective recruitment to spinal mitochondria
- 2004
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Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 43:1, s. 5-17
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Tidskriftsartikel (refereegranskat)abstract
- One cause of amyotrophic lateral sclerosis (ALS) is mutation in ubiquitously expressed copper/zinc superoxide dismutase (SOD1), but the mechanism of toxicity to motor neurons is unknown. Multiple disease-causing mutants, but not wild-type SOD1, are now demonstrated to be recruited to mitochondria, but only in affected tissues. This is independent of the copper chaperone for SOD1 and dismutase activity. Highly preferential association with spinal cord mitochondria is seen in human ALS for a mutant SOD1 that accumulates only to trace cytoplasmic levels. Despite variable proportions that are successfully imported, nearly constant amounts of SOD1 mutants and covalently damaged adducts of them accumulate as apparent import intermediates and/or are tightly aggregated or crosslinked onto integral membrane components on the cytoplasmic face of those mitochondria. These findings implicate damage from action of spinal cord-specific factors that recruit mutant SOD1 to spinal mitochondria as the basis for their selective toxicity in ALS.
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| 5. |
- Muhr, J, et al.
(författare)
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Convergent inductive signals specify midbrain, hindbrain, and spinal cord identity in gastrula stage chick embryos.
- 1999
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Ingår i: Neuron. - 0896-6273 .- 1097-4199. ; 23:4, s. 689-702
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Tidskriftsartikel (refereegranskat)abstract
- In the chick embryo, neural cells acquire midbrain, hindbrain, and spinal cord character over a approximately 6 hr period during gastrulation. The convergent actions of four signals appear to specify caudal neural character. Fibroblast growth factors (FGFs) and a paraxial mesoderm-caudalizing (PMC) activity are involved, but neither signal is sufficient to induce any single region. FGFs act indirectly by inducing mesoderm that expresses PMC and retinoid activity and also directly on prospective neural cells, in combination with PMC activity and a rostralizing signal, to induce midbrain character. Hindbrain character emerges from cells that possess the potential to acquire midbrain character upon exposure to higher levels of PMC activity. Induction of spinal cord character appears to involve PMC and retinoid activities.
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| 6. |
- Nicolas, Aude, et al.
(författare)
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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
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Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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| 7. |
- Nyberg, Lars
(författare)
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Intact frontal memory effect in older age and dementia
- 2004
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Ingår i: Neuron. - Cambridge, Mass. : Cell Press. - 0896-6273 .- 1097-4199. ; 42:5, s. 701-702
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Older adults and demented patients show preserved functioning on certain tests of implicit memory. In this issue of Neuron, Lustig and Buckner demonstrate that both groups show comparable repetition-based effects on response time and prefrontal activity relative to younger adults.
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| 8. |
- Olcese, Umberto, et al.
(författare)
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Cellular and synaptic architecture of multisensory integration in the mouse neocortex
- 2013
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Ingår i: Neuron. - : Elsevier BV. - 0896-6273 .- 1097-4199. ; 79:3, s. 579-593
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Tidskriftsartikel (refereegranskat)abstract
- Multisensory integration (MI) is crucial for sensory processing, but it is unclear how MI is organized in cortical microcircuits. Whole-cell recordings in a mouse visuotactile area located between primary visual and somatosensory cortices revealed that spike responses were less bimodal than synaptic responses but displayed larger multisensory enhancement. MI was layer and cell type specific, with multisensory enhancement being rare in the major class of inhibitory interneurons and in the output infragranular layers. Optogenetic manipulation of parvalbumin-positive interneuron activity revealed that the scarce MI of interneurons enables MI in neighboring pyramids. Finally, single-cell resolution calcium imaging revealed a gradual merging of modalities: unisensory neurons had higher densities toward the borders of the primary cortices, but were located in unimodal clusters in the middle of the cortical area. These findings reveal the role of different neuronal subcircuits in the synaptic process of MI in the rodent parietal cortex.
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| 9. |
- Schacter, Daniel L., et al.
(författare)
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Endel Tulving (1927-2023) [Obituary]
- 2023
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Ingår i: Neuron. - : Elsevier. - 0896-6273 .- 1097-4199. ; 111:22, s. 3502-3504
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 10. |
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