Sensory axons projecting to the central nervous system are organized into topographic maps that represent the locations of sensory stimuli. In some sensory systems, even adjacent sensory axons are arranged topographically, forming “fine-scale” topographic maps. Although several broad molecular gradients are known to instruct coarse topography, we know little about the molecular signaling that regulates fine-scale topography at the level of two adjacent axons. Here, we provide evidence that trans-synaptic BMP signaling mediates local inter-neuronal communication to regulate fine-scale topography in the nociceptive system of Drosophila larvae. We first show that the topographic separation of the axon terminals of adjacent nociceptors requires their common postsynaptic target, the A08n neurons. This phenotype is recapitulated by knockdown of the BMP ligand, Dpp, in these neurons. In addition, removing the type-II BMP receptors or their effector (Mad transcription factor) in single nociceptors impairs the fine...

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Adolescent inhibition of thalamo-cortical projections from postnatal day P20-50 leads to long-lasting deficits in prefrontal-cortex function and cognition in the adult mouse. While this suggests a role of thalamic activity in prefrontal-cortex maturation, it is unclear how inhibition of these projections affect prefrontal circuitry during adolescence. Here, we used chemogenetic tools to inhibit thalamo-prefrontal projections in male/female mice from P20-35 and measured synaptic inputs to prefrontal pyramidal neurons by layer (either II/III or V/VI) and projection target (MD, NAc or callosal mPFC) twenty-four hours later using slice physiology. We chose mPFC and MD-projecting cells as they are largely distinguished by cortical layer (II/III versus V/VI, respectively) and NAc-projecting cells as they span both layers and therefore provide a within-layer comparison for the other two populations. We found a decrease in the frequency of excitatory and inhibitory currents in layer-II/III-nucleus-accumbens (NAc) ...

Reverberation, a ubiquitous feature of real-world acoustic environments, exhibits statistical regularities that human listeners leverage to self-orient, facilitate auditory perception, and understand their environment. Despite the extensive research on sound source representation in the auditory system, it remains unclear how the brain represents real-world reverberant environments. Here, we characterized the neural response to reverberation of varying realism by applying multivariate pattern analysis to electroencephalographic (EEG) brain signals. Human listeners (12 male and 8 female) heard speech samples convolved with real-world and synthetic reverberant impulse responses and judged whether the speech samples were in a “real” or “fake” environment, focusing on the reverberant background rather than the properties of speech itself. Participants distinguished real from synthetic reverberation with ∼75% accuracy; EEG decoding reveals a multistage decoding time course, with dissociable components early in ...

ATP1A3 is a Na,K-ATPase gene expressed specifically in neurons in the brain. Human mutations are dominant and produce an unusually wide spectrum of neurological phenotypes, most notably rapid-onset dystonia- parkinsonism (RDP) and alternating hemiplegia childhood (AHC). Here we compared heterozygotes of two mouse lines, a line with little or no expression ( Atp1a 3tm1Ling/+) and a knock-in expressing p.Asp801Tyr (D801Y, Atp1a3 +/D801Y). Both mouse lines had normal lifespans, but Atp1a3 +/D801Y had mild perinatal mortality contrasting with D801N mice ( Atp1a3 +/D801N), which had high mortality. The phenotypes of Atp1a 3tm1Ling/+ and Atp1a3 +/D801Y were different, and testing of each strain was tailored to its symptom range. Atp1a 3tm1Ling/+ mice displayed little at baseline, but repeated ethanol intoxication produced hyperkinetic motor abnormalities not seen in littermate controls. Atp1a3 +/D801Y mice displayed robust phenotypes: hyperactivity, diminished posture consistent with hypotonia, and deficiencies ...

Animal studies consistently demonstrate that testosterone is protective against pain in multiple models, including an animal model of activity-induced muscle pain . In this model, females develop widespread muscle hyperalgesia, and reducing testosterone levels in males results in widespread muscle hyperalgesia. Widespread pain is believed to be mediated by changes in the central nervous system, including the rostral ventromedial medulla (RVM). The enzyme that converts testosterone to estradiol, aromatase, is highly expressed in the RVM. Therefore, we hypothesized that testosterone is converted by aromatase to estradiol locally in the RVM to prevent development of widespread muscle hyperalgesia in male mice. This was tested through pharmacological inhibition of estrogen receptors (ER), aromatase, or ER-α in the RVM which resulted in contralateral hyperalgesia in male mice (C57BL/6J). ER inhibition in the RVM had no effect on hyperalgesia in female mice. As prior studies show modulation of estradiol signalin...

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Adults heard recordings of two spatially separated speakers reading newspaper and magazine articles. They were asked to listen to one of them and ignore the other, and EEG was recorded to assess their neural processing. Machine learning extracted neural sources that tracked the target and distractor speakers at three levels: the acoustic envelope of speech (delta- and theta-band modulations), lexical frequency for individual words, and the contextual predictability of individual words estimated by GPT-4 and earlier lexical models. To provide a broader view of speech perception, half of the subjects completed a simultaneous visual task, and the listeners included both native and non-native English speakers. Distinct neural components were extracted for these levels of auditory and lexical processing, demonstrating that native English speakers had greater target-distractor separation compared to non-native English speakers on most measures, and that lexical processing was reduced by the visual task. Moreover...

Recent advances in extracellular electrophysiology now facilitate the recording of spikes from hundreds or thousands of neurons simultaneously. This has necessitated both the development of new computational methods for spike sorting and better methods to determine spike sorting accuracy. One longstanding method of assessing the false discovery rate (FDR) of spike sorting – the rate at which spikes are assigned to the wrong cluster – has been the rate of inter-spike-interval (ISI) violations. Despite their near ubiquitous usage in spike sorting, our understanding of how exactly ISI violations relate to FDR, as well as best practices for using ISI violations as a quality metric, remain limited. Here, we describe an analytical solution that can be used to predict FDR from ISI violation rate. We test this model in silico through Monte Carlo simulation, and apply it to publicly available spike-sorted electrophysiology datasets. We find that the relationship between ISI violation rate and FDR is highly nonlinea...

Adolescent inhibition of thalamocortical projections from postnatal days P20 to 50 leads to long-lasting deficits in prefrontal cortex function and cognition in the adult mouse. While this suggests a role of thalamic activity in prefrontal cortex maturation, it is unclear how inhibition of these projections affects prefrontal circuitry during adolescence. Here, we used chemogenetic tools to inhibit thalamoprefrontal projections in male/female mice from P20 to P35 and measured synaptic inputs to prefrontal pyramidal neurons by layer (either II/III or V/VI) and projection target (mediodorsal thalamus (MD), nucleus accumbens (NAc), or callosal prefrontal projections) 24 h later using slice physiology. We found a decrease in the frequency of excitatory and inhibitory currents in layer II/III NAc and layer V/VI MD-projecting neurons while layer V/VI NAc-projecting neurons showed an increase in the amplitude of excitatory and inhibitory currents. Regarding cortical projections, the frequency of inhibitory but no...