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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...
Perception can change nonlinearly with stimulus contrast, and perceptual threshold may depend on the direction of contrast change. Such hysteresis effects in neurometric functions provide a signature of perceptual awareness. We recorded brain activity with functional neuroimaging in observers exposed to gradual contrast changes of initially hidden visual stimuli. Lateral occipital, frontal, and parietal...
Interactions between different sensory modalities can be observed in unimodal areas of the cortex, as revealed by recent neuroimaging studies. A new report by Macaluso and colleagues (Macaluso et al., 2002 [this issue of Neuron]) shows that crossmodal effects of tactile stimulation in visual cortex critically depend on the spatial congruence of multisensory inputs. This work is discussed in relation...
Previous studies have shown that pharmacological activation of presynaptic kainate receptors at glutamatergic synapses facilitates or depresses transmission in a dose-dependent manner. However, the only synaptically activated kainate autoreceptor described to date is facilitatory. Here, we describe a kainate autoreceptor that depresses synaptic transmission. This autoreceptor is present at developing...
Neuronal kainate receptors are assembled from subunits with dissimilar specificities for agonists and antagonists. The composite biophysical behavior of heteromeric kainate receptors is determined by intersubunit interactions whose nature is unclear. Here we use dysiherbaine, a selective kainate receptor agonist, to show that GluR5 subunits assembled in heteromeric GluR5/KA-2 kainate receptor complexes...
Ca2+-permeable AMPARs are inwardly rectifying due to block by intracellular polyamines. Neuronal activity regulates polyamine synthesis, yet whether this affects Ca2+-AMPAR-mediated synaptic transmission is unknown. We test whether 4 hr of increased visual stimulation regulates glutamatergic retino-tectal synapses in Xenopus tadpoles. Tectal neurons containing Ca2+-AMPARs form a gradient along the...
Pathologic alterations in the microtubule-associated protein tau have been implicated in a number of neurodegenerative disorders, including Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and frontotemporal dementia (FTD). Here, we show that tau overexpression, in combination with phosphorylation by the Drosophila glycogen synthase kinase-3 (GSK-3) homolog and wingless pathway component...
We review the challenges and recent progress in elucidating the physiological basis of animal magnetoreception. Behavioral and theoretical studies suggest a link between photoreception and magnetoreception in some animals. Neurophysiological studies have the potential to prove this link and identify the location of and the mechanism underlying the magnetoreception system.
Functionally distinct types of neurons develop in stereotypical positions in the vertebrate spinal cord. The mechanisms that generate this diversity have been well studied in the ventral and intermediate regions of the spinal cord, while dorsal cells have received less attention. In this issue of Neuron, two papers focusing on dorsal interneuron development (Gross et al., 2002; Müller et al., 2002)...
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