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Mating induces changes in the receptivity and egg-laying behavior in Drosophila females, primarily due to a peptide pheromone called sex peptide which is transferred with the sperm into the female reproductive tract during copulation. Whereas sex peptide is generally believed to modulate fruitless-GAL4-expressing neurons in the central nervous system to produce behavioral changes, we found that six...
Energy use, mainly to reverse ion movements in neurons, is a fundamental constraint on brain information processing. Trafficking of mitochondria to locations in neurons where there are large ion fluxes is essential for powering neural function. Mitochondrial trafficking is regulated by Ca 2+ entry through ionotropic glutamate receptors, but the underlying mechanism is unknown. We show that...
The primate dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) focus attention on relevant signals and suppress noise in cognitive tasks. However, their synaptic interactions and unique roles in cognitive control are unknown. We report that two distinct pathways to DLPFC area 9, one from the neighboring area 46 and the other from the functionally distinct ACC, similarly innervate...
The molecular mechanisms underlying the homeostatic modulation of presynaptic neurotransmitter release remain largely unknown. In a screen, we isolated mutations in Drosophila ephexin (Rho-type guanine nucleotide exchange factor) that disrupt the homeostatic enhancement of presynaptic release following impairment of postsynaptic glutamate receptor function at the Drosophila neuromuscular junction...
Separate studies have implicated the lateral habenula (LHb) or amygdala-related regions in processing aversive stimuli, but their relationships to each other and to appetitive motivational systems are poorly understood. We show that neurons in the recently identified GABAergic rostromedial tegmental nucleus (RMTg), which receive a major LHb input, project heavily to midbrain dopamine neurons, and...
The Wechsler Adult Intelligence Scale (WAIS) assesses a wide range of cognitive abilities and impairments. Factor analyses have documented four underlying indices that jointly comprise intelligence as assessed with the WAIS: verbal comprehension (VCI), perceptual organization (POI), working memory (WMI), and processing speed (PSI). We used nonparametric voxel-based lesion-symptom mapping in 241 patients...
Migraine is a common disabling brain disorder. A subtype of migraine with aura (familial hemiplegic migraine type 1: FHM1) is caused by mutations in Ca V 2.1 (P/Q-type) Ca 2+ channels. Knockin mice carrying a FHM1 mutation show increased neuronal P/Q-type current and facilitation of induction and propagation of cortical spreading depression (CSD), the phenomenon that underlies migraine...
Delineating the molecular basis of synapse development is crucial for understanding brain function. Cocultures of neurons with transfected fibroblasts have demonstrated the synapse-promoting activity of candidate molecules. Here, we performed an unbiased expression screen for synaptogenic proteins in the coculture assay using custom-made cDNA libraries. Reisolation of NGL-3/LRRC4B and neuroligin-2...
Ultimately, whether or not a neuron produces a spike determines its contribution to local computations. In response to brief stimuli the probability a neuron will fire can be described by its input-output function, which depends on the net balance and timing of excitatory and inhibitory currents. While excitatory and inhibitory synapses are plastic, most studies examine plasticity of subthreshold...
Adaptation is a hallmark of sensory function. Adapting optimally requires matching the dynamics of adaptation to those of changes in the stimulus distribution. Here we show that the dynamics of adaptation in the responses of mouse retinal ganglion cells depend on stimulus history. We hypothesized that the accumulation of evidence for a change in the stimulus distribution controls the dynamics of adaptation,...
Early during neuromuscular development, acetylcholine receptors (AChRs) accumulate at the center of muscle fibers, precisely where motor growth cones navigate and synapses eventually form. Here, we show that Wnt11r binds to the zebrafish unplugged/MuSK ectodomain to organize this central muscle zone. In the absence of such a zone, prepatterned AChRs fail to aggregate and, as visualized by live-cell...
The study of human learning is complicated by the myriad of processing elements involved in conducting any behavioral task. In the case of visual perceptual learning, there has been significant controversy regarding the task processes that guide the formation of this learning. However, there is a developing consensus that top-down, task-related factors are required for such learning to take place...
Most heritable behavioral traits have a complex genetic basis, but few multigenic traits are understood at a molecular level. Here we show that the C. elegans strains N2 and CB4856 have opposite behavioral responses to simultaneous changes in environmental O 2 and CO 2 . We identify two quantitative trait loci (QTL) that affect this trait and map each QTL to a single-gene polymorphism...
In this issue of Neuron, Seitz et al. show that humans exhibit enhanced perceptual discrimination for visual stimuli that have been repeatedly paired with reward under conditions of suppressed awareness. These findings challenge the view that awareness and focused attention are necessary for perceptual learning.
Beginning approximately a decade and a half ago, it was suggested that some structures that are considered to be part of the “medial temporal lobe memory system” could play a role in perception as well. The implications of this view, interpreted broadly, are that medial temporal lobe structures may be understood as an extension of the ventral visual stream and that their functions cannot be described...
Migraine is thought to be triggered by excessive neocortical neuronal excitability that leads to cortical spreading depression. In this issue of Neuron, Tottene et al. study a mouse model of familial hemiplegic migraine type 1, and provide evidence for the hyperactivity of P/Q-type calcium channel-mediated cortical glutamatergic synaptic transmission as an underlying mechanism for the susceptibility...
Synaptogenesis is thought to be mediated by cell adhesion proteins, which induce the initial contact between an axon and its target cell and subsequently recruit and organize the presynaptic and postsynaptic protein machinery required for synaptic transmission. A new study by Linhoff and colleagues in this issue of Neuron identifies adhesion proteins of the LRRTM family as novel synaptic organizers.
A dominant view in the learning and memory literature states that a subset of anatomically related structures within the medial temporal lobe (MTL), including the hippocampus, entorhinal, perirhinal, and parahippocampal cortices, forms a functionally related system specialized for declarative memory but not for perception. However, recent reports challenge this view, suggesting instead that the medial...
Although we know a great deal about how the brain processes information about aversive and appetitive stimuli, it is not clear how these two systems interact to guide behavior. In this issue of Neuron, Jhou and colleagues identify a region in the midbrain tegmentum that signals aversive events and inhibits midbrain dopamine neurons.
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