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Neuropilin-1 and neuropilin-2 bind differentially to different class 3 semaphorins and are thought to provide the ligand-binding moieties in receptor complexes mediating repulsive responses to these semaphorins. Here, we have studied the function of neuropilin-2 through analysis of a neuropilin-2 mutant mouse, which is viable and fertile. Repulsive responses of sympathetic and hippocampal neurons...
Mitochondria are thought to be important in clearing calcium from synaptic terminals. It is unclear, however, whether the principal role of mitochondria in presynaptic calcium handling is to take up Ca2+ directly or to fuel Ca2+ removal by other mechanisms. We used patch clamp techniques and fluorescence imaging to examine calcium clearance mechanisms, including mitochondrial uptake, in single synaptic...
The auxiliary β subunit is essential for functional expression of high voltage-activated Ca2+ channels. This effect is partly mediated by a facilitation of the intracellular trafficking of α1 subunit toward the plasma membrane. Here, we demonstrate that the I-II loop of the α1 subunit contains an endoplasmic reticulum (ER) retention signal that severely restricts the plasma membrane incorporation...
The mlenapts mutation causes temperature-dependent blockade of action potentials resulting from decreased abundance of para-encoded Na+ channels. Although maleless (mle) encodes a double-stranded RNA (dsRNA) helicase, exactly how mlenapts affects para expression remained uncertain. Here, we show that para transcripts undergo adenosine-to-inosine (A-to-I) RNA editing via a mechanism that apparently...
Bipolar cells in the vertebrate retina have been characterized as nonspiking interneurons. Using patch-clamp recordings from goldfish retinal slices, we find, however, that the morphologically well-defined Mb1 bipolar cell is capable of generating spikes. Surprisingly, in dark-adapted retina, spikes were reliably evoked by light flashes and had a long (1–2 s) refractory period. In light-adapted retina,...
Piccolo is a novel component of the presynaptic cytoskeletal matrix (PCM) assembled at the active zone of neurotransmitter release. Analysis of its primary structure reveals that Piccolo is a multidomain zinc finger protein structurally related to Bassoon, another PCM protein. Both proteins were found to be shared components of glutamatergic and GABAergic CNS synapses but not of the cholinergic neuromuscular...
In the Drosophila peripheral nervous system, proneural genes direct the formation of different types of sensory organs. Here, we show that amos is a novel proneural gene that promotes multiple dendritic (MD) neuron formation. amos encodes a basic-helix-loop-helix (bHLH) protein of the Atonal family. During embryonic development, amos is expressed in patches of ectodermal cells, and the expression...
The relationship between adhesive interactions across the synaptic cleft and synaptic function has remained elusive. At certain CNS synapses, pre- to postsynaptic adhesion is mediated at least in part by neural (N-) cadherin. Here, we demonstrate that upon depolarization of hippocampal neurons in culture by K+ treatment, or application of NMDA or α-latrotoxin, synaptic N-cadherin dimerizes and becomes...
The role of the target cell in neurotrophin-induced modifications of glutamatergic synaptic transmission was examined in cultured hippocampal neurons. Brain-derived neurotrophic factor (BDNF) induced rapid and persistent potentiation of evoked glutamate release when the postsynaptic neuron was glutamatergic, or excitatory (E→E), but not when it was GABAergic, or inhibitory (E→I). This target-specific...
Syntaxin-1 is a key component of the synaptic vesicle docking/fusion machinery that forms the SNARE complex with VAMP/synaptobrevin and SNAP-25. Identifying proteins that modulate SNARE complex formation is critical for understanding the molecular mechanisms underlying neurotransmitter release and its modulation. We have cloned and characterized a protein called syntaphilin that is selectively expressed...
Anterior forebrain (AF) neurons become selective for song as songbirds learn to produce a copy of a memorized tutor song. We report that development of selectivity is compromised when birds are prevented from matching their output to the tutor song. Finches with denervated vocal organs developed stable song, but it usually did not resemble the tutor song. In those birds, numerous neurons in Area X...
Neuregulin-1 (NRG-1) signaling has been implicated in inductive interactions between pre- and postsynaptic partners during synaptogenesis. We used gene targeting to selectively disrupt cysteine-rich domain– (CRD-) containing NRG-1 isoforms. In CRD-NRG-1−/− mice, peripheral projections defasciculated and displayed aberrant branching patterns within their targets. Motor nerve terminals were transiently...
α-Synuclein (α-Syn) is a 14 kDa protein of unknown function that has been implicated in the pathophysiology of Parkinson's disease (PD). Here, we show that α-Syn−/− mice are viable and fertile, exhibit intact brain architecture, and possess a normal complement of dopaminergic cell bodies, fibers, and synapses. Nigrostriatal terminals of α-Syn−/− mice display a standard pattern of dopamine (DA) discharge...
Although nerve growth factor (NGF) is a crucial factor in the activity-dependent development and plasticity of visual cortex, its role in synaptic efficacy changes is largely undefined. We demonstrate that the maintenance phase of long-term potentiation (LTP) is blocked by local application of exogenous NGF in rat visual cortex at an early stage of postnatal development. Long-term depression (LTD)...
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