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The motor system may generate automated movements, such as walking, by combining modular spinal motor synergies. However, it remains unknown whether a modular neuronal architecture is sufficient to generate the unique flexibility of human finger movements, which rely on cortical structures. Here we show that finger movements evoked by transcranial magnetic stimulation (TMS) of the primary motor cortex...
The head direction cell system is composed of multiple regions associated with the hippocampal formation. The dynamics of head direction tuning curves (HDTCs) were compared with those of hippocampal place fields. In both familiar and cue-altered environments, as a rat ran an increasing number of laps on a track, the center of mass (COM) of the HDTC tended to shift backward, similar to shifting observed...
Our knowledge of how developing dendrites attain their mature state is still rudimentary. In this issue of Neuron, Mumm et al. rely on time-lapsed analysis of ingrowing dendrites of retinal ganglion cells in transgenic zebrafish to show that this process is much more specific than has been suspected.
The expression mechanism of long-term potentiation (LTP) remains controversial. Here we combine electrophysiology and Ca 2+ imaging to examine the role of silent synapses in LTP expression. Induction of LTP fails to change p r at these synapses but instead mediates an unmasking process that is sensitive to the inhibition of postsynaptic membrane fusion. Once unmasked, however, further...
Zn 2+ is thought to modulate neurotransmission by affecting currents mediated by ligand-gated ion channels and transmitter reuptake by Na + -dependent transporter systems. Here, we examined the in vivo relevance of Zn 2+ neuromodulation by producing knockin mice carrying the mutation D80A in the glycine receptor (GlyR) α1 subunit gene (Glra1). This substitution selectively...
Son of sevenless (Sos) is a dual specificity guanine nucleotide exchange factor (GEF) that regulates both Ras and Rho family GTPases and thus is uniquely poised to integrate signals that affect both gene expression and cytoskeletal reorganization. Here, using genetics, biochemistry, and cell biology, we demonstrate that Sos is recruited to the plasma membrane, where it forms a ternary complex with...
Voltage-activated potassium (K v ) channels contain a central pore domain that is partially surrounded by four voltage-sensing domains. Recent X-ray structures suggest that the two domains lack extensive protein-protein contacts within presumed transmembrane regions, but whether this is the case for functional channels embedded in lipid membranes remains to be tested. We investigated domain...
Homeostatic signaling systems are thought to interface with the mechanisms of neural plasticity to achieve stable yet flexible neural circuitry. However, the time course, molecular design, and implementation of homeostatic signaling remain poorly defined. Here we demonstrate that a homeostatic increase in presynaptic neurotransmitter release can be induced within minutes following postsynaptic glutamate...
Experience-dependent plasticity is a prominent feature of the mammalian visual cortex. Although such neural changes are most evident during development, adult cortical circuits can be modified by a variety of manipulations, such as perceptual learning and visual deprivation. Elucidating the underlying mechanisms at the cellular and synaptic levels is an essential step in understanding neural plasticity...
Targeting of axons and dendrites to particular synaptic laminae is an important mechanism by which precise patterns of neuronal connectivity are established. Although axons target specific laminae during development, dendritic lamination has been thought to occur largely by pruning of inappropriately placed arbors. We discovered by in vivo time-lapse imaging that retinal ganglion cell (RGC) dendrites...
Intensity-tuned neurons, characterized by their nonmonotonic response-level function, may play important roles in the encoding of sound intensity-related information. The synaptic mechanisms underlying intensity tuning remain unclear. Here, in vivo whole-cell recordings in rat auditory cortex revealed that intensity-tuned neurons, mostly clustered in a posterior zone, receive imbalanced tone-evoked...
The gating mechanism of K v channels is not known. In this issue of Neuron, Soler-Llavina et al. present fascinating results that support the concept of relatively independent voltage-sensing modules. However, they also find that its interactions with the pore domain are rather complex, with specific S4–S5 intersubunit contacts underlying the concerted transition leading to the channel opening.
Phospholipase Cβ (PLCβ) isozymes represent a family of molecules that link G protein-coupled receptors (GPCRs) to an intracellular signaling network. Here, we investigated the function of PLCβ isozymes in sensory neurons by using mutant mice deficient for specific PLCβ family members. Expression analysis indicated that PLCβ3, one of the four isoforms, is predominantly expressed in a subpopulation...
Mutations in LRRK2 underlie an autosomal-dominant, inherited form of Parkinson's disease (PD) that mimics the clinical features of the common “sporadic” form of PD. The LRRK2 protein includes putative GTPase, protein kinase, WD40 repeat, and leucine-rich repeat (LRR) domains of unknown function. Here we show that PD-associated LRRK2 mutations display disinhibited kinase activity and induce a progressive...
Alternative splicing choices are governed by splicing regulatory protein interactions with splicing silencer and enhancer elements present in the pre-mRNA. However, the prediction of these choices from genomic sequence is difficult, in part because the regulators can act as either enhancers or silencers. A recent study describes how for a particular neuronal splicing regulatory protein, Nova, the...
It has long been known that the synaptic vesicles of certain glutamatergic terminals, as well as some inhibitory terminals, are richly supplied with zinc ions, yet the functional role of this pool of zinc in synaptic transmission has remained elusive. In this issue of Neuron, Hirzel et al. provide direct in vivo evidence that endogenous zinc is required for proper functioning of neuronal circuitry...
We combined local photolysis of caged compounds with fluorescence imaging to visualize molecular diffusion within dendrites of cerebellar Purkinje cells. Diffusion of a volume marker, fluorescein dextran, within spiny dendrites was remarkably slow in comparison to its diffusion in smooth dendrites. Computer simulations indicate that this retardation is due to a transient trapping of molecules within...
Synaptic homeostasis is a phenomenon that prevents the nervous system from descending into chaos. In this issue of Neuron, Frank et al. overturn the notion that synaptic homeostasis at Drosophila NMJs is a slow developmental process. They report that postsynaptic changes are offset within minutes by a homeostatic increase in neurotransmitter release that requires the presynaptic Ca 2+ channel...
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