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The colony-stimulating factor 1 receptor (CSF1R) is a key regulator of myeloid lineage cells. Genetic loss of the CSF1R blocks the normal population of resident microglia in the brain that originates from the yolk sac during early development. However, the role of CSF1R signaling in microglial homeostasis in the adult brain is largely unknown. To this end, we tested the effects of selective CSF1R...
The ocular motility disorder “Congenital fibrosis of the extraocular muscles type 1” (CFEOM1) results from heterozygous mutations altering the motor and third coiled-coil stalk of the anterograde kinesin, KIF21A. We demonstrate that Kif21a knockin mice harboring the most common human mutation develop CFEOM. The developing axons of the oculomotor nerve’s superior division stall in the proximal nerve;...
Activity-dependent alterations in the strength of an individual glutamatergic synapse are often accompanied by changes in the size and shape of the postsynaptic terminal. Two studies in this issue of Neuron, Meyer et al. (2014) and Bosch et al. (2014), shed new light on the mechanisms and signaling pathways underlying structural long-term potentiation.
A variety of attention-related effects have been demonstrated in primary auditory cortex (A1). However, an understanding of the functional role of higher auditory cortical areas in guiding attention to acoustic stimuli has been elusive. We recorded from neurons in two tonotopic cortical belt areas in the dorsal posterior ectosylvian gyrus (dPEG) of ferrets trained on a simple auditory discrimination...
Protein synthesis is crucial for both persistent synaptic plasticity and long-term memory. De novo protein expression can be restricted to specific neurons within a population, and to specific dendrites within a single neuron. Despite its ubiquity, the functional benefits of spatial protein regulation for learning are unknown. We used computational modeling to study this problem. We found that spatially...
Subsynaptic structures such as bouton, active zone, postsynaptic density (PSD) and dendritic spine, are highly correlated in their dimensions and also correlate with synapse strength. Why this is so and how such correlations are maintained during synaptic plasticity remains poorly understood. We induced spine enlargement by two-photon glutamate uncaging and examined the relationship between spine,...
The spatiotemporal activities of astrocyte Ca 2+ signaling in mature neuronal circuits remain unclear. We used genetically encoded Ca 2+ and glutamate indicators as well as pharmacogenetic and electrical control of neurotransmitter release to explore astrocyte activity in the hippocampal mossy fiber pathway. Our data revealed numerous localized, spontaneous Ca 2+ signals in...
Cortical GABAergic interneurons have essential roles for information processing and their dysfunction is implicated in neuropsychiatric disorders. Transcriptional codes are elucidating mechanisms of interneuron specification in the MGE (a subcortical progenitor zone), which regulate their migration, integration, and function within cortical circuitry. Lhx6, a LIM-homeodomain transcription factor,...
Polyglutamine expansion in the androgen receptor causes Kennedy’s disease. Two recent reports, Cortes et al. (2014) in this issue of Neuron and Lieberman et al. (2014) in Cell Reports, raise the possibility that targeting expression of the mutant protein in skeletal muscle, instead of the nervous system, may mitigate manifestations of this disorder.
Thalamocortical (TC) connectivity is reorganized by thalamic inputs during postnatal development; however, the dynamic characteristics of TC reorganization and the underlying mechanisms remain unexplored. We addressed this question using dendritic refinement of layer 4 (L4) stellate neurons in mouse barrel cortex (barrel cells) as a model; dendritic refinement of L4 neurons is a critical component...
Social media has created new pathways for postpublication peer review, which regularly leads to corrections. Such online discussions are often resisted by authors and editors, however, and efforts to formalize postpublication peer review have not yet resonated with scientific communities.
In layer 6 (L6), a principal output layer of the mammalian cerebral cortex, a population of excitatory neurons defined by the NTSR1-Cre mouse line inhibit cortical responses to visual stimuli. Here we show that of the two major types of excitatory neurons existing in L6, the NTSR1-Cre line selectively targets those whose axons innervate both cortex and thalamus and not those whose axons remain within...
Synapses store information by long-lasting modifications of their structure and molecular composition, but the precise chronology of these changes has not been studied at single-synapse resolution in real time. Here we describe the spatiotemporal reorganization of postsynaptic substructures during long-term potentiation (LTP) at individual dendritic spines. Proteins translocated to the spine in four...
Microglia are highly dynamic components of the innate immune system. In this issue of Neuron, Elmore et al. (2014) report that global depletion of microglia triggers mobilization of latent microglial progenitors throughout the CNS, resulting in rapid repopulation.
NMDA receptor (NMDAR)-induced excitotoxicity is thought to contribute to the cell death associated with certain neurodegenerative diseases, stroke, epilepsy, and traumatic brain injury. Targeting NMDARs therapeutically is complicated by the fact that cell signaling downstream of their activation can promote cell survival and plasticity as well as excitotoxicity. However, research over the past decade...
X-linked spinal and bulbar muscular atrophy (SBMA) is characterized by adult-onset muscle weakness and lower motor neuron degeneration. SBMA is caused by CAG-polyglutamine (polyQ) repeat expansions in the androgen receptor (AR) gene. Pathological findings include motor neuron loss, with polyQ-AR accumulation in intranuclear inclusions. SBMA patients exhibit myopathic features, suggesting a role for...
Neural circuit formation relies on interactions between axons and cells within the target field. While it is well established that target-derived signals act on axons to regulate circuit assembly, the extent to which axon-derived signals control circuit formation is not known. In the Drosophila visual system, anterograde signals numerically match R1–R6 photoreceptors with their targets by controlling...
Sexually dimorphic behaviors, qualitative or quantitative differences in behaviors between the sexes, result from the activity of a sexually differentiated nervous system. Sensory cues and sex hormones control the entire repertoire of sexually dimorphic behaviors, including those commonly thought to be charged with emotion such as courtship and aggression. Such overarching control mechanisms regulate...
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