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Mechanotransduction, the conversion of physical forces into biochemical signals, is essential for various physiological processes such as the conscious sensations of touch and hearing, and the unconscious sensation of blood flow. Mechanically activated (MA) ion channels have been proposed as sensors of physical force, but the identity of these channels and an understanding of how mechanical force...
Dipeptide repeat (DPR) proteins are toxic in various models of FTD/ALS with GGGGCC (G4C2) repeat expansion. However, it is unclear whether nuclear G4C2 RNA foci also induce neurotoxicity. Here, we describe a Drosophila model expressing 160 G4C2 repeats (160R) flanked by human intronic and exonic sequences. Spliced intronic 160R formed nuclear G4C2 sense RNA foci in glia and neurons about ten times...
Frontal neocortex is thought to support our highest intellectual abilities, including our ability to plan and enact a sequence of tasks toward a desired goal. In everyday life, such task sequences are abstract in that they do not require consistent movement sequences and are often assembled “on the fly.” Yet, remarkably little is known about the necessity of frontal sub-regions for such control. Participants...
Intelligence relies on our ability to find appropriate sequences of decisions in complex problem spaces. The efficiency of a problem solver depends on the speed of its individual decisions and the number of decisions it can explore in parallel. It remains unknown whether the primate brain can consider multiple decisions at the same time. We therefore trained monkeys to navigate through a decision...
The social welfare provided by cooperation depends on the enforcement of social norms. Determining blameworthiness and assigning a deserved punishment are two cognitive cornerstones of norm enforcement. Although prior work has implicated the dorsolateral prefrontal cortex (DLPFC) in norm-based judgments, the relative contribution of this region to blameworthiness and punishment decisions remains poorly...
Analysis of de novo CNVs (dnCNVs) from the full Simons Simplex Collection (SSC) (N = 2,591 families) replicates prior findings of strong association with autism spectrum disorders (ASDs) and confirms six risk loci (1q21.1, 3q29, 7q11.23, 16p11.2, 15q11.2-13, and 22q11.2). The addition of published CNV data from the Autism Genome Project (AGP) and exome sequencing data from the SSC and the Autism Sequencing...
Spatial and temporal features of synaptic inputs engage integration mechanisms on multiple scales, including presynaptic release sites, postsynaptic dendrites, and networks of inhibitory interneurons. Here we investigate how these mechanisms cooperate to filter synaptic input in hippocampal area CA1. Dendritic recordings from CA1 pyramidal neurons reveal that proximal inputs from CA3 as well as distal...
Coupling between voltage-gated Ca2+ influx and synaptic vesicle exocytosis is essential for rapid evoked neurotransmission. Acuna et al. show that the knockout of RIM-BPs, which are key structural components of this coupling, decreases the reliability of evoked neurotransmitter release.
Dopamine (DA) neurons are thought to facilitate learning by signaling reward prediction errors (RPEs), the discrepancy between actual and expected reward. However, how RPEs are calculated remains unknown. It has been hypothesized that DA neurons receive RPE signals from the lateral habenula. Here, we tested how lesions of the habenular complex affect the response of optogenetically identified DA neurons...
How do the components of neuronal circuits collaborate to select combinations of synaptic inputs from multiple pathways? In this issue of Neuron, Milstein et al. (2015) uncover mechanisms of synaptic facilitation and dendritic inhibition that cooperate to provide filtering for co-active inputs of distinct origins.
The dynamic interactions between hippocampus and amygdala are critical for emotional memory. Theta synchrony between these structures occurs during fear memory retrieval and may facilitate synaptic plasticity, but the cellular mechanisms are unknown. We report that interneurons of the mouse basal amygdala are activated during theta network activity or optogenetic stimulation of ventral CA1 pyramidal...
Real-life decisions often involve multiple intermediate choices among competing, interdependent options. Lorteije et al. (2015) introduce a new paradigm for dissecting the neural strategies underlying such decisions.
Forming distinct representations and memories of multiple contexts and episodes is thought to be a crucial function of the hippocampal-entorhinal cortical network. The hippocampal dentate gyrus (DG) and CA3 are known to contribute to these functions, but the role of the entorhinal cortex (EC) is poorly understood. Here, we show that Ocean cells, excitatory stellate neurons in the medial EC layer II...
In the retina, rod and cone photoreceptors form distinct connections with different classes of downstream bipolar cells. However, the molecular mechanisms responsible for their selective connectivity are unknown. Here we identify a cell-adhesion protein, ELFN1, to be essential for the formation of synapses between rods and rod ON-bipolar cells in the primary rod pathway. ELFN1 is expressed selectively...
Ultrafast neurotransmitter release requires tight colocalization of voltage-gated Ca2+ channels with primed, release-ready synaptic vesicles at the presynaptic active zone. RIM-binding proteins (RIM-BPs) are multidomain active zone proteins that bind to RIMs and to Ca2+ channels. In Drosophila, deletion of RIM-BPs dramatically reduces neurotransmitter release, but little is known about RIM-BP function...
Brains are optimized for processing ethologically relevant sensory signals. However, few studies have characterized the neural coding mechanisms that underlie the transformation from natural sensory information to behavior. Here, we focus on acoustic communication in Drosophila melanogaster and use computational modeling to link natural courtship song, neuronal codes, and female behavioral responses...
The state of the brain and body constantly varies on rapid and slow timescales. These variations contribute to the apparent noisiness of sensory responses at both the neural and the behavioral level. Recent investigations of rapid state changes in awake, behaving animals have provided insight into the mechanisms by which optimal sensory encoding and behavioral performance are achieved. Fluctuations...
Cortical function is regulated by a strikingly diverse array of local-circuit inhibitory neurons. We evaluated how optogenetically activating somatostatin- and parvalbumin-positive interneurons subtractively or divisively suppressed auditory cortical cells’ responses to tones. In both awake and anesthetized animals, we found that activating either family of interneurons produced mixtures of divisive...
To attract females during courtship, Drosophila melanogaster males sing songs with motifs of varying temporal structure. In this issue of Neuron, Clemens et al. (2015) identify a song feature indicating male fitness and propose a neural mechanism for how it may be extracted from the auditory signal by female flies.
Topographic maps in visual processing areas maintain the spatial order of the visual world. Molecular cues and neuronal activity both play critical roles in map formation, but their interaction remains unclear. Here, we demonstrate that when molecular- and activity-dependent cues are rendered nearly equal in force, they drive topographic mapping stochastically. The functional and anatomical representation...
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