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Phosphoinositide-specific phospholipase C (PLC) isozymes play roles in a diversity of processes including Drosophila phototransduction. In fly photoreceptor cells, the PLCβ encoded by norpA is critical for activation of TRP channels. Here, we describe a PLCβ regulator, STOPS, which encodes a SOCS box protein. Mutation of stops resulted in a reduced concentration of NORPA and a defect in stopping signaling...
Two studies in this issue of Neuron (Kwon and Castillo and Rebola et al.) show that the mossy fiber-CA3 pyramidal neuron synapse, a hippocampal synapse well known for its presynaptic plasticity, exhibits a novel form of long-term potentiation of NMDAR-mediated currents, which is induced and expressed postsynaptically.
Studies of the Drosophila visual system have provided valuable insights into the function and regulation of phototransduction signaling pathways. Much of this work has stemmed from or relied upon the genetic tools offered by the Drosophila system. In this issue of Neuron, Wang and colleagues and Acharya and colleagues have further exploited the Drosophila genetic system to characterize two new phototransduction...
The mossy fiber to CA3 pyramidal cell synapse (mf-CA3) provides a major source of excitation to the hippocampus. Thus far, these glutamatergic synapses are well recognized for showing a presynaptic, NMDA receptor-independent form of LTP that is expressed as a long-lasting increase of transmitter release. Here, we show that in addition to this “classical” LTP, mf-CA3 synapses can undergo a form of...
Two groups of participants, one susceptible to posthypnotic amnesia (PHA) and the other not, viewed a movie. A week later, they underwent hypnosis in the fMRI scanner and received a suggestion to forget the movie details after hypnosis until receiving a reversal cue. The participants were tested twice for memory for the movie and for the context in which it was shown, under the posthypnotic suggestion...
Although much traditional sensory research has studied each sensory modality in isolation, there has been a recent explosion of interest in causal interplay between different senses. Various techniques have now identified numerous multisensory convergence zones in the brain. Some convergence may arise surprisingly close to low-level sensory-specific cortex, and some direct connections may exist even...
MicroRNAs (miRNAs) are highly expressed in vertebrate neural tissues, but the contribution of specific miRNAs to the development and function of different neuronal populations is still largely unknown. We report that miRNAs are required for terminal differentiation of olfactory precursors in both mouse and zebrafish but are dispensable for proper function of mature olfactory neurons. The repertoire...
Ionotropic glutamate receptor (iGluR) subunits contain a large N-terminal domain (NTD) that precedes the agonist-binding domain (ABD) and participates in subunit oligomerization. In NMDA receptors (NMDARs), the NTDs of NR2A and NR2B subunits also form binding sites for the endogenous inhibitor Zn 2+ ion. Although these allosteric sites have been characterized in detail, the molecular mechanisms...
Electrical activity plays a crucial role in neuronal circuit assembly. Activation of NMDA receptors induces the elevation of intracellular calcium, resulting in the modulation of calcium-calmodulin-dependent protein kinases (CaMKs). The CaMK pathway regulates synaptogenesis by driving the formation of dendritic spines. However, the molecular effectors downstream of this pathway have remained poorly...
Neutral ceramidase, a key enzyme of sphingolipid metabolism, hydrolyzes ceramide to sphingosine. These sphingolipids are critical structural components of cell membranes and act as second messengers in diverse signal transduction cascades. Here, we have isolated and characterized functional null mutants of Drosophila ceramidase. We show that secreted ceramidase functions in a cell-nonautonomous manner...
Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder caused by expansion of a translated CAG repeat in the N terminus of the huntingtin (htt) protein. Here we describe the generation and characterization of a full-length HD Drosophila model to reveal a previously unknown disease mechanism that occurs early in the course of pathogenesis, before expanded htt is imported into...
Neuronal activity augments maturation of mushroom-shaped spines to form excitatory synapses, thereby strengthening synaptic transmission. We have delineated a Ca 2+ -signaling pathway downstream of the NMDA receptor that stimulates calmodulin-dependent kinase kinase (CaMKK) and CaMKI to promote formation of spines and synapses in hippocampal neurons. CaMKK and CaMKI form a multiprotein signaling...
Sensory processing in the brain is thought to have evolved to encode naturally occurring stimuli efficiently. We report an adaptation in binocular cortical neurons that reflects the tight constraints imposed by the geometry of 3D vision. We show that the widely used binocular energy model predicts that neurons dedicate part of their dynamic range to impossible combinations of left and right images...
In addition to the classical, center/surround receptive field of neurons in the lateral geniculate nucleus (LGN), there is an extraclassical, nonlinear surround that can strongly suppress LGN responses. This form of suppression likely plays an important role in adjusting the gain of LGN responses to visual stimuli. We performed experiments in alert and anesthetized macaque monkeys to quantify extraclassical...
Circadian clock proteins are modified in many different ways. The best-studied posttranslational modification is phosphorylation, with well-known kinases and phosphatases regulating the function and stability of clock proteins. Degradation of these proteins usually involves ubiquitylation or sumoylation, and some of the relevant E3 ligases are known. In addition, Hirayama et al. recently identified...
The physiological conditions under which adenosine A 2A receptors modulate synaptic transmission are presently unclear. We show that A 2A receptors are localized postsynaptically at synapses between mossy fibers and CA3 pyramidal cells and are essential for a form of long-term potentiation (LTP) of NMDA-EPSCs induced by short bursts of mossy fiber stimulation. This LTP spares AMPA-EPSCs...
Place-specific firing in the hippocampus is determined by path integration-based spatial representations in the grid-cell network of the medial entorhinal cortex. Output from this network is conveyed directly to CA1 of the hippocampus by projections from principal neurons in layer III, but also indirectly by axons from layer II to the dentate gyrus and CA3. The direct pathway is sufficient for spatial...
The fidelity with which spinal motor neurons innervate their limb target muscles helps to coordinate motor behavior, but the mechanisms that determine precise patterns of nerve-muscle connectivity remain obscure. We show that Nkx6 proteins, a set of Hox-regulated homeodomain transcription factors, are expressed by motor pools soon after motor neurons leave the cell cycle, before the formation of muscle...
The vesicular glutamate transporters VGLUT1 and VGLUT2 fill synaptic vesicles with glutamate, an essential prerequisite for glutamatergic transmission in the CNS. In contrast, the third isoform, VGLUT3, is not confined to glutamatergic neurons, and its function has remained enigmatic. In this issue of Neuron, Seal et al. show that mice lacking VGLUT3 are profoundly deaf and exhibit nonconvulsive seizures.
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