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“Grid cells” encode an animal’s location and direction of movement in 2D physical environments via regularly repeating receptive fields. Constantinescu et al. (2016) report the first evidence of grid cells for 2D conceptual spaces. The work has exciting implications for mental representation and shows how detailed neural-coding hypotheses can be tested with bulk population-activity measures.
Adaptation is fundamental to life. All organisms adapt over timescales that span from evolution to generations and lifetimes to moment-by-moment interactions. The nervous system is particularly adept at rapidly adapting to change, and this in fact may be one of its fundamental principles of organization and function. Rapid forms of sensory adaptation have been well documented across all sensory modalities...
A recent study by Wang et al. (2016a) claims that the low-frequency variant NR1H3 p.Arg415Gln is sufficient to cause multiple sclerosis in certain individuals and determines a patient’s likelihood of primary progressive disease. We sought to replicate this finding in the International MS Genetics Consortium (IMSGC) patient collection, which is 13-fold larger than the collection of Wang et al. (2016a),...
Many neurodegenerative proteinopathies share a common pathogenic mechanism: the abnormal accumulation of disease-related proteins. As growing evidence indicates that reducing the steady-state levels of disease-causing proteins mitigates neurodegeneration in animal models, we developed a strategy to screen for genes that decrease the levels of tau, whose accumulation contributes to the pathology of...
Homeostatic scaling adjusts the strength of synaptic connections up or down in response to large changes in input. To identify the landscape of proteomic changes that contribute to opposing forms of homeostatic plasticity, we examined the plasticity-induced changes in the newly synthesized proteome. Cultured rat hippocampal neurons underwent homeostatic up-scaling or down-scaling. We used BONCAT (bio-orthogonal...
Neural responses in the visual cortex are variable, and there is now an abundance of data characterizing how the magnitude and structure of this variability depends on the stimulus. Current theories of cortical computation fail to account for these data; they either ignore variability altogether or only model its unstructured Poisson-like aspects. We develop a theory in which the cortex performs probabilistic...
Haploinsufficiency of Retinoic Acid Induced 1 (RAI1) causes Smith-Magenis syndrome (SMS), which is associated with diverse neurodevelopmental and behavioral symptoms as well as obesity. RAI1 encodes a nuclear protein but little is known about its molecular function or the cell types responsible for SMS symptoms. Using genetically engineered mice, we found that Rai1 preferentially occupies DNA regions...
Efficient retrograde access to projection neurons for the delivery of sensors and effectors constitutes an important and enabling capability for neural circuit dissection. Such an approach would also be useful for gene therapy, including the treatment of neurodegenerative disorders characterized by pathological spread through functionally connected and highly distributed networks. Viral vectors, in...
In this issue of Neuron, Orbán et al. (2016) test whether the brain represents probabilities by sampling: do neurons interpret the world by generating causal explanations of sense data and quickly sample different interpretations over time? Orbán et al. (2016) find agreement between this model’s predictions and neural data.
Lasagna-Reeves et al. (2016) demonstrate that preventing the kinase Nuak1 from phosphorylating the microtubule-associated protein tau reduces the level of potentially pathogenic tau species in brain, a novel therapeutic strategy that could help counteract Alzheimer’s disease and several other neurological disorders.
The cerebral cortex computes through the canonical microcircuit that connects six stacked layers; however, how cortical processing streams operate in vivo, particularly in the higher association cortex, remains elusive. By developing a novel MRI-assisted procedure that reliably localizes recorded single neurons at resolution of six individual layers in monkey temporal cortex, we show that transformation...
Sam Wang is a pioneer in using statistical methods to analyze U.S. presidential election polls. In this election season interview with Neuron, he discusses diagnosing partisan gerrymandering, his research on the cerebellum, and how he analyzes polls with high accuracy.
Injuries to the adult CNS often result in permanent disabilities because neurons lose the ability to regenerate their axon during development. Here, whole transcriptome sequencing and bioinformatics analysis followed by gain- and loss-of-function experiments identified Cacna2d2, the gene encoding the Alpha2delta2 subunit of voltage-gated calcium channels (VGCCs), as a developmental switch that limits...
Long-term changes of neurotransmitter release are critical for proper brain function. However, the molecular mechanisms underlying these changes are poorly understood. While protein synthesis is crucial for the consolidation of postsynaptic plasticity, whether and how protein synthesis regulates presynaptic plasticity in the mature mammalian brain remain unclear. Here, using paired whole-cell recordings...
New research published in Neuron describes assignment of cortical layer to single neurons recorded in awake monkeys. Applying the procedure to perirhinal cortex, Koyano et al. (2016) found marked and unsuspected differences among layers in the coding of associative memory signals.
The neocortex undergoes extensive developmental growth, but how its architecture adapts to expansion remains largely unknown. Here, we investigated how early born Cajal-Retzius (CR) neurons, which regulate the assembly of cortical circuits, maintain a dense superficial distribution in the growing neocortex. We found that CR cell density is sustained by an activity-dependent importation of olfactory...
In this issue of Neuron, Tedeschi et al. (2016) describe the voltage-gated calcium channel subunit alpha2delta2 as a developmental switch from axon elongation to synapse formation and transmission that doubles as a suppressor of axon regeneration, providing a molecular clue for the synaptic stabilization hypothesis of CNS regeneration failure.
In this issue of Neuron, Younts et al. (2016) demonstrate that activation of presynaptic CB1 receptors by retrograde endocannabinoid signaling stimulates protein synthesis in axon terminals to induce long-term depression of hippocampal inhibitory transmission.
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