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Synaptic plasticity is a multistep process in which rapid, early phases eventually give way to slower, more enduring stages. Diverse forms of synaptic change share a common requirement for protein synthesis in the late stages of plasticity, which are often associated with structural rearrangements. Ocular dominance plasticity in the primary visual cortex (V1) is a long-lasting form of activity-dependent...
Experience-dependent remodelling of neural connections progresses through stages, and early phases eventually give way to later long-lasting ones. The transition from early to late stages, often associated with structural changes, depends on protein synthesis. Suppression of cortical but not geniculate protein synthesis blocks ocular dominance plasticity at its earliest stage, suggesting that structural...
In vivo whole-cell recordings revealed that during repeated stimulation, synaptic responses to deflection of facial whiskers rapidly adapt. Extracellular recordings in the somatosensory thalamus revealed that part of the adaptation occurs subcortically, but because cortical adaptation is stronger and recovers more slowly, cortical mechanisms must also contribute. Trains of sensory stimuli that produce...
Wiring a brain presents a formidable problem because neural circuits require an enormous number of fast and durable connections. We propose that evolution was likely to have optimized neural circuits to minimize conduction delays in axons, passive cable attenuation in dendrites, and the length of “wire” used to construct circuits, and to have maximized the density of synapses. Here we ask the question:...
We analyzed the formation of neuromuscular junctions (NMJs) in individual muscles of the mouse embryo. Skeletal muscles can be assigned to one of two distinct classes of muscles, termed “Fast Synapsing” (FaSyn) and “Delayed Synapsing” (DeSyn) muscles, which differ significantly with respect to the initial focal clustering of postsynaptic AChRs, the timing of presynaptic maturation, and the maintenance...
Neuronal adaptation to repetitive sensory stimuli is ubiquitous in the mammalian cortex. Despite its prevalence, the cellular mechanisms underlying this basic physiological property remain a matter of dispute. In this issue of Neuron, Chung et al. provide conclusive evidence that depression of thalamocortical synapses may play a significant role in the expression of neuronal adaptation in the rat...
Many central neurons possess large acid-activated currents, yet their molecular identity is unknown. We found that eliminating the acid sensing ion channel (ASIC) abolished H+-gated currents in hippocampal neurons. Neuronal H+-gated currents and transient acidification are proposed to play a role in synaptic transmission. Investigating this possibility, we found ASIC in hippocampus, in synaptosomes,...
We have recently proposed a center-periphery organization based on resolution needs, in which objects engaging in recognition processes requiring central-vision (e.g., face-related) are associated with center-biased representations, while objects requiring large-scale feature integration (e.g., buildings) are associated with periphery-biased representations. Here we tested this hypothesis by comparing...
CREB is critical for long-lasting synaptic and behavioral plasticity in invertebrates. Its role in the mammalian hippocampus is less clear. We have interfered with CREB family transcription factors in region CA1 of the dorsal hippocampus. This impairs learning in the Morris water maze, which specifically requires the dorsal hippocampus, but not context conditioning, which does not. The deficit is...
In this issue of Neuron, Gurevich et al. (2002) report different patterns of 5-HT2C pre-mRNA editing in suicide victims, as compared to controls. Treatment of mice with fluoxetine alters the pattern of 5-HT2C transcript editing in the direction opposite that observed for suicide victims. The authors speculate on a possible serotonergic mechanism controlling 5-HT2C pre-mRNA editing.
The sigma receptor is a novel protein that mediates the modulation of ion channels by psychotropic drugs through a unique transduction mechanism depending neither on G proteins nor protein phosphorylation. The present study investigated sigma receptor signal transduction by reconstituting responses in Xenopus oocytes. Sigma receptors modulated voltage-gated K+ channels (Kv1.4 or Kv1.5) in different...
To understand brain development, we must learn how synapse formation shapes functional neural circuits. At the heart of this process lies the nascent synapse—an enigmatic structure spanning the developmental gap between initial cell-cell contact and the mature synapse. New experimental techniques are beginning to illuminate the processes involved in synaptogenesis, but much remains to be learned,...
Ca2+ influx through voltage-gated channels initiates the exocytotic fusion of synaptic vesicles to the plasma membrane. Here we show that RIM binding proteins (RBPs), which associate with Ca2+ channels in hair cells, photoreceptors, and neurons, interact with α1D (L type) and α1B (N type) Ca2+ channel subunits. RBPs contain three Src homology 3 domains that bind to proline-rich motifs in α1 subunits...
CRE-binding protein (CREB) belongs to a family of transcription factors that mediates stimulus-dependent gene expression in neuronal and non-neuronal cells. Here we show that CREB is phosphorylated on its transcriptional regulatory site, Ser-133, in vivo in a neurotrophin-dependent manner. In mice harboring a null mutation in the Creb gene, sensory neurons exhibit excess apoptosis and degeneration,...
Homomeric assembly of Kir5.1, an inward-rectifying K+ channel subunit, is believed to be nonfunctional, although the subunit exists abundantly in the brain. We show that HEK293T cells cotransfected with Kir5.1 and PSD-95 exhibit a Ba2+-sensitive inward-rectifying K+ current. Kir5.1 coexpressed with PSD-95 located on the plasma membrane in a clustered manner, while the Kir5.1 subunit expressed alone...
Five adenosines within the coding sequence of the serotonin 2C receptor (5-HT2C) pre-mRNA are converted to inosines by RNA editing (named A, B, C′ (E), C, and D sites). In human prefrontal cortex (PFC), the most abundant 5-HT2C mRNA sequences result from editing at the A site, or from the editing combinations AC′C, ABCD, and ABD. In suicide victims with a history of major depression, C′ site editing...
The DEG/ENaC ion channel family contributes to channels of striking functional diversity. Neuronally expressed family members include the C. elegans degenerins that mediate touch and are thought to be mechanically gated, and the mammalian ASICs, which are gated by protons. ASICs affect a range of sensory functions that includes perception of gentle touch, harsh touch, heat, sour taste, and pain. Family...
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