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CASK acts as a coactivator for Tbr-1, an essential transcription factor in cerebral cortex development. Presently, the molecular mechanism of the CASK coactivation effect is unclear. Here, we report that CASK binds to another nuclear protein, CINAP, which binds histones and facilitates nucleosome assembly. CINAP, via its interaction with CASK, forms a complex with Tbr-1, regulating expression of the...
The Ena/VASP family of proteins consists of adaptor molecules that localize to subcellular sites of actin polymerization. The role of Ena/VASP proteins in the regulation of cell motility and axon outgrowth has been controversial. Recently, these proteins have been proposed to function as ''anticapping'' factors, which may have differential effects on filopodial versus lammelipodial actin-based protrusions...
Drosophila olfactory receptor neurons (ORNs) elaborate a precise internal representation of the external olfactory world in the antennal lobe (AL), a structure analagous to the vertebrate olfactory bulb. ORNs expressing the same odorant receptor innervate common targets in a highly organized neuropilar structure inside the AL, the glomerulus. During normal development, ORNs target to specific regions...
BSC1, which was originally identified by its sequence similarity to voltage-gated Na + channels, encodes a functional voltage-gated cation channel whose properties differ significantly from Na + channels. BSC1 has slower kinetics of activation and inactivation than Na + channels, it is more selective for Ba 2+ than for Na + , it is blocked by Cd 2 ...
The cadherin superfamily of cell adhesion molecules have been proposed to play important roles in determining synaptic specificity in developing nervous systems. We examine the function of N-cadherin in Drosophila second order olfactory projection neurons (PNs), each of which must selectively target their dendrites to one of ~50 glomeruli. Our results do not support an instructive role for N-cadherin...
Axon guidance requires signal transduction of extracellular cues through the plasma membrane for directional motility. Here we present evidence that cholesterol- and sphingolipid-enriched membrane microdomains (lipid rafts) mediate specific guidance responses of nerve growth cones. Disruption of lipid rafts by various approaches targeting cholesterol or gangliosides selectively abolished growth cone...
Genetically encoded probes show great promise in permitting functional imaging of specified neuronal populations in the intact nervous system, yet their in vivo application has been limited. Here, we have targeted expression of synapto-pHluorin, a pH-sensitive protein that reports synaptic vesicle fusion, to olfactory sensory neurons in mouse. Synapto-pHluorin selectively labeled presynaptic terminals...
We have addressed the role of occipital and somatosensory cortex in a tactile discrimination task. Sight-ed and congenitally blind subjects rated the rough-ness and distance spacing for a series of raised dot patterns. When judging roughness, intermediate dot spacings were perceived as being the most rough, while distance judgments generated a linear relation. Low-frequency rTMS applied to somatosensory...
Rapid identification of behaviorally relevant objects is important for survival. In humans, the neural computations for visually discriminating complex objects involve inferior temporal cortex (IT). However, less detailed but faster form processing may also occur in a phylogenetically older subcortical visual system that terminates in the amygdala. We used binocular rivalry to present stimuli without...
The active zone protein RIM1α is required both for maintaining normal probability of neurotransmitter release and for long-term presynaptic potentiation at brain synapses. We now demonstrate that RIM1α -/- mice exhibit normal coordination and anxiety-related behaviors but display severely impaired learning and memory. Mice with a synaptotagmin 1 mutation, which selectively lowers...
Prior exposure to a moving grating of high contrast led to a substantial and persistent reduction in the contrast sensitivity of neurons in the lateral geniculate nucleus (LGN) of macaque. This slow contrast adaptation was potent in all magnocellular (M) cells but essentially absent in parvocellular (P) cells and neurons that received input from S cones. Simultaneous recordings of M cells and the...
Mutations in presenilins are the major cause of familial Alzheimer's disease, but the pathogenic mechanism by which presenilin mutations cause memory loss and neurodegeneration remains unclear. Here we demonstrate that conditional double knockout mice lacking both presenilins in the postnatal forebrain exhibit impairments in hippocampal memory and synaptic plasticity. These deficits are associated...
Human vision adapts to the contrast of patterns by changing its sensitivity, but the origins of this perceptual adaptation have been disputed. In this issue of Neuron, Solomon et al. show that contrast adaptation in the primate arises mostly in the retina for the magnocellular pathway and mostly in the cortex for the parvocellular pathway. It appears that adaptation arises most strongly at sites that...
β subunits of voltage-gated calcium channels (VGCCs) regulate channel trafficking and function, thereby shaping the intensity and duration of intracellular changes in calcium. β subunits share limited sequence homology with the Src homology 3-guanylate kinase (SH3-GK) module of membrane-associated guanylate kinases (MAGUKs). Here, we show biochemical similarities between β subunits and MAGUKs, revealing...
Ena/VASP proteins play important roles in axon outgrowth and guidance. Ena/VASP activity regulates the assembly and geometry of actin networks within fibroblast lamellipodia. In growth cones, Ena/VASP proteins are concentrated at filopodia tips, yet their role in growth cone responses to guidance signals has not been established. We found that Ena/VASP proteins play a pivotal role in formation and...
Lipid rafts are thought to serve as plasma membrane platforms for localized trafficking and signaling. Recent findings reported by Guirland et al. in this issue of Neuron and by Gomez-Mouton in a recent issue of JCB support a direct role of lipid microdomains in organizing spatial signaling during axon guidance and cell chemotaxis by concentrating the gradient-sensing machinery at the leading edge.
Calcium/calmodulin-dependent protein kinase II (CaMKII) is a multifunctional enzyme that is very critical for synaptic plasticity and memory formation. Although significant progress has been made in understanding the role of postsynaptic CaMKII in synaptic plasticity, very little is known about its presynaptic function during plasticity changes. Here we report that KN-93, a membrane-permeable CaMKII...
Synaptic vesicle endocytosis is believed to require calcium and the GTPase dynamin. We now report a form of rapid endocytosis (RE) in dorsal root ganglion (DRG) neurons that, unlike previously described forms of endocytosis, is independent of calcium and dynamin. The RE is tightly coupled to calcium-independent but voltage-dependent secretion (CIVDS). Using FM dye and capacitance measurements, we...
Cysteine string protein α (CSPα)-an abundant synaptic vesicle protein that contains a DNA-J domain characteristic of Hsp40 chaperones-is thought to regulate Ca 2+ channels and/or synaptic vesicle exocytosis. We now show that, in young mice, deletion of CSPα does not impair survival and causes no significant changes in presynaptic Ca 2+ currents or synaptic vesicle exocytosis...
Presenilins are considered to be the catalytic subunits of the γ-secretase complex and are therefore drug targets for Alzheimer's disease. They are also essential for the fine tuning of the immunological system and for memory and synaptic plasticity. Genetic ablation in the forebrain results in a progressive neurodegenerative process that is independent from Aβ generation. The question arises as to...
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