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We have investigated the source(s) and targeting of components to PNS nodes of Ranvier. We show adhesion molecules are freely diffusible within the axon membrane and accumulate at forming nodes from local sources, whereas ion channels and cytoskeletal components are largely immobile and require transport to the node. We further characterize targeting of NF186, an adhesion molecule that pioneers node...
Dendrites of the same neuron usually avoid each other. Some neurons also repel similar neurons through dendrite-dendrite interaction to tile the receptive field. Nonoverlapping coverage based on such contact-dependent repulsion requires dendrites to compete for limited space. Here we show that Drosophila class IV dendritic arborization (da) neurons, which tile the larval body wall, grow their dendrites...
The histone deacetylase HDAC5 has been shown to regulate behavioral adaptations to cocaine. In this issue of Neuron, Taniguchi et al. (2012) describe a cAMP-dependent signaling pathway that regulates nuclear accumulation of HDAC5, suggesting a mechanism to couple cocaine with changes in HDAC5 function.
The response of cortical neurons to a sensory stimulus is shaped by the network in which they are embedded. Here we establish a role of parvalbumin (PV)-expressing cells, a large class of inhibitory neurons that target the soma and perisomatic compartments of pyramidal cells, in controlling cortical responses. By bidirectionally manipulating PV cell activity in visual cortex we show that these neurons...
NMDA receptor activation leads to clathrin-dependent endocytosis of postsynaptic AMPA receptors. Although this process controls long-term depression (LTD) induction in the hippocampus, how it is regulated by neuronal activities is not completely clear. Here, we show that Ca 2+ influx through the NMDA receptor activates calcineurin and protein phosphatase 1 to dephosphorylate phosphatidylinositol...
Over the past two decades, research has identified extrasynaptic GABA A receptor populations that enable neurons to sense the low ambient GABA concentrations present in the extracellular space in order to generate a form of tonic inhibition not previously considered in studies of neuronal excitability. The importance of this tonic inhibition in regulating states of consciousness is highlighted...
As a precursor to the selection of a stimulus for gaze and attention, a midbrain network categorizes stimuli into “strongest” and “others.” The categorization tracks flexibly, in real time, the absolute strength of the strongest stimulus. In this study, we take a first-principles approach to computations that are essential for such categorization. We demonstrate that classical feedforward lateral...
In this issue of Neuron, Mysore and Knudsen (2012) describe a simple, anatomically supported circuit that can categorize stimuli into “strongest” and “others,” regardless of their absolute strength. Such flexible categorization cannot be achieved by lateral inhibition alone but also requires that the inhibitory neurons reciprocally inhibit each other.
MicroRNAs (miRNA) are implicated in brain development and function but the underlying mechanisms have been difficult to study in part due to the cellular heterogeneity in neural circuits. To systematically analyze miRNA expression in neurons, we have established a miRNA tagging and affinity-purification (miRAP) method that is targeted to cell types through the Cre-loxP binary system in mice. Our studies...
In addition to activity-dependent neurotransmission, neurons can undergo spontaneous activity-independent neurotransmitter release with low probability. In this issue of Neuron, Ramirez et al. (2012) now identify the noncanonical endosomal SNARE Vps10p-tail-interactor1a (Vti1a) as a regulator of spontaneously fusing vesicles.
Recent studies suggest that synaptic vesicles (SVs) giving rise to spontaneous neurotransmission are distinct from those that carry out evoked release. However, the molecular basis of this dichotomy remains unclear. Here, we focused on two noncanonical SNARE molecules, Vps10p-tail-interactor-1a (vti1a) and VAMP7, previously shown to reside on SVs. Using simultaneous multicolor imaging at individual...
We perceive real-world objects as three-dimensional (3D), yet it is unknown which brain area underlies our ability to perceive objects in this way. The macaque inferotemporal (IT) cortex contains neurons that respond selectively to 3D structures defined by binocular disparity. To examine the causal role of IT in the categorization of 3D structures, we electrically stimulated clusters of IT neurons...
Neuroimaging is central to the quest for a biological foundation of psychiatric diagnosis but so far has not yielded clinically relevant biomarkers for mental disorders. This review addresses potential reasons for this limitation and discusses refinements of paradigms and analytic techniques that may yield improved diagnostic and prognostic accuracy. Neuroimaging can also be used to probe genetically...
Peripheral axons from auditory spiral ganglion neurons (SGNs) form an elaborate series of radially and spirally oriented projections that interpret complex aspects of the auditory environment. However, the developmental processes that shape these axon tracts are largely unknown. Radial bundles are comprised of dense SGN fascicles that project through otic mesenchyme to form synapses within the cochlea...
Chromatin remodeling by histone deacetylases (HDACs) is a key mechanism regulating behavioral adaptations to cocaine use. We report here that cocaine and cyclic adenosine monophosphate (cAMP) signaling induce the transient nuclear accumulation of HDAC5 in rodent striatum. We show that cAMP-stimulated nuclear import of HDAC5 requires a signaling mechanism that involves transient, protein phosphatase...
The bottom-up contribution to the allocation of exogenous attention is a saliency map, whose neural substrate is hard to identify because of possible contamination by top-down signals. We obviated this possibility using stimuli that observers could not perceive, but that nevertheless, through orientation contrast between foreground and background regions, attracted attention to improve a localized...
Dendrites achieve characteristic spacing patterns during development to ensure appropriate coverage of territories. Mechanisms of dendrite positioning via repulsive dendrite-dendrite interactions are beginning to be elucidated, but the control, and importance, of dendrite positioning relative to their substrate is poorly understood. We found that dendritic branches of Drosophila dendritic arborization...
Here we provide evidence that revises the inhibitory circuit diagram of the cerebellar cortex. It was previously thought that Golgi cells, interneurons that are the sole source of inhibition onto granule cells, were exclusively coupled via gap junctions. Moreover, Golgi cells were believed to receive GABAergic inhibition from molecular layer interneurons (MLIs). Here we challenge these views by optogenetically...
In this issue of Neuron, Nicolas et al. (2012) show that JAK2/STAT3 signaling, a canonical pathway for transmitting information from the cell membrane to the nucleus, is critical for NMDAR-LTD, even in the absence of new DNA transcription.
Transient increases in nucleus accumbens (NAc) dopamine concentration are observed when animals are presented with motivationally salient stimuli and are theorized to energize reward seeking. They arise from high-frequency firing of dopamine neurons in the ventral tegmental area (VTA), which also results in the release of endocannabinoids from dopamine cell bodies. In this context, endocannabinoids...
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