The ability to comprehend phrases is an essential integrative property of the brain. Here we evaluate the neural processes that enable the transition from single word processing to a minimal compositional scheme. Previous research has reported conflicting timing effects of composition, and disagreement persists with respect to inferior frontal and posterior temporal contributions. To address these issues, 19 patients (10 male, 19 female) implanted with penetrating depth or surface subdural intracranial electrodes heard auditory recordings of adjective-noun, pseudoword-noun and adjective-pseudoword phrases and judged whether the phrase matched a picture. Stimulus-dependent alterations in broadband gamma activity, low frequency power and phase-locking values across the language-dominant left hemisphere were derived. This revealed a mosaic located on the lower bank of the posterior superior temporal sulcus (pSTS), in which closely neighboring cortical sites displayed exclusive sensitivity to either lexicality...

Paternal environmental perturbations can influence the physiology and behavior of offspring. For example, our previous work showed reduced cocaine reinforcement in male, but not female, progeny of rat sires that self-administered cocaine. The information transfer from sire to progeny may occur through epigenetic marks in sperm, encompassing alterations in small noncoding RNAs including microRNAs (miRNAs) and/or DNA methylation. Here, no reliable changes in miRNAs in the sperm of cocaine- relative to saline-experienced sires were identified. In contrast, 272 differentially methylated regions were observed in sperm between these groups. Two hypomethylated promoter regions in the sperm of cocaine-experienced rats were upstream of cyclin-dependent kinase inhibitor 1a ( Cdkn1a ). Cdkn1a mRNA also was selectively increased in the nucleus accumbens of cocaine-sired male (but not female) offspring. Cocaine self-administration also enhanced Cdkn1a expression in the accumbens of cocaine-sired rats. These results sug...

Neural phase-locking to temporal fluctuations is a fundamental and unique mechanism by which acoustic information is encoded by the auditory system. The perceptual role of this metabolically expensive mechanism, the neural phase-locking to temporal fine structure (TFS) in particular, is debated. Although hypothesized, it is unclear whether auditory perceptual deficits in certain clinical populations are attributable to deficits in TFS coding. Efforts to uncover the role of TFS have been impeded by the fact that there are no established assays for quantifying the fidelity of TFS coding at the individual level. While many candidates have been proposed, for an assay to be useful, it should not only intrinsically depend on TFS coding, but should also have the property that individual differences in the assay reflect TFS coding per se over and beyond other sources of variance. Here, we evaluate a range of behavioral and electroencephalogram (EEG)-based measures as candidate individualized measures of TFS sensit...

Identifying the spinal circuits controlling locomotion is critical for unravelling the mechanisms controlling the production of gaits. Development of the circuits governing left-right coordination relies on axon guidance molecules such as ephrins and netrins. To date, no other class of proteins have been shown to play a role during this process. Here, we have analyzed hop mice, which walk with a characteristic hopping gait using their hindlimbs in synchrony. Fictive locomotion experiments suggest that a local defect in the ventral spinal cord contributes to the aberrant locomotor phenotype. Hop mutant spinal cords had severe morphologic defects, including the absence of the ventral midline and a poorly defined border between white and gray matter. The hop mice represent the first model where, exclusively found in the lumbar domain, the left and right components of the central pattern generators (CPGs) are fused with a synchronous hindlimb gait as a functional consequence. These defects were associated with...

Electrical synapses couple inhibitory neurons across the brain, underlying a variety of functions that are modifiable by activity. Despite recent advances, many functions and contributions of electrical synapses within neural circuitry remain underappreciated. Among these are the sources and impacts of electrical synapse asymmetry. Using multi-compartmental models of neurons coupled through dendritic electrical synapses, we investigated intrinsic factors that contribute to effective synaptic asymmetry and that result in modulation of spike timing and synchrony between coupled cells. We show that electrical synapse location along a dendrite, input resistance, internal dendritic resistance, or directional conduction of the electrical synapse itself each alter asymmetry as measured by coupling between cell somas. Conversely, we note that asymmetrical gap junction (GJ) conductance can be masked by each of these properties. Furthermore, we show that asymmetry modulates spike timing and latency of coupled cells ...

When faced with multiple potential movement options, individuals either reach directly to one of the options, or initiate a reach intermediate between the options. It remains unclear why people generate these two types of behaviors. Using the go-before-you-know task (commonly used to study behavior under choice uncertainty) in humans, we examined two key questions. First, do these two types of responses actually reflect distinct movement strategies? If so, the relative desirability (i.e., weighing the success likelihood vs the attainable reward) of the two target options would not need to be computed identically for direct and intermediate reaches. We showed that indeed, when reward and success likelihood differed between the two options, reach direction was preferentially biased toward different directions for direct versus intermediate reaches. Importantly, this suggests that the computation of subjective values depends on the choice of movement strategy. Second, what drives individual differences in how...

It has been shown that P3b is not a signature of perceptual awareness per se but is instead more closely associated with postperceptual processing ([Cohen et al., 2020][1]). Here, we seek to investigate whether human participants’ attentional states are different in the report and the no-report conditions. This difference in attentional states, if exists, may lead to degraded consciousness of the stimuli in the no-report condition, and it therefore remains unknown whether the disappearance of P3b is because of a lack of reportability or degraded consciousness. Results of our experiment 1 showed that participants did experience degraded contents of consciousness in the no-report condition. However, results of experiment 2 showed that the degraded contents of consciousness did not influence the amplitude of P3b. These findings strengthen the claim that P3b is not a signature of perceptual awareness but is associated with postperceptual processing. [1]: #ref-14

Modern molecular and biochemical neuroscience studies require analysis of specific cellular populations derived from brain tissue samples to disambiguate cell type-specific events. This is particularly true in the analysis of minority glial populations in the brain, such as microglia, which may be obscured in whole tissue analyses. Microglia have central functions in development, aging, and neurodegeneration and are a current focus of neuroscience research. A long-standing concern for glial biologists using in vivo models is whether cell isolation from CNS tissue could introduce ex vivo artifacts in microglia, which respond quickly to changes in the environment. Mouse microglia were purified by magnetic-activated cell sorting (MACS), as well as cytometer-based and cartridge-based fluorescence-activated cell sorting (FACS) approaches to compare and contrast performance. The Cx3cr1-NuTRAP mouse model was used to provide an endogenous fluorescent microglial marker and a microglial-specific translatome profile...

Target reward influences motor planning strategies through modulation of movement vigor. Considering current theories of sensorimotor control suggesting that movement planning consists in selecting a goal-directed control strategy, we sought to investigate the influence of reward on feedback control. Here, we explored this question in three human reaching experiments. First, we altered the explicit reward associated with the goal target and found an overall increase in feedback gains for higher target rewards, highlighted by larger velocities, feedback responses to external loads, and background muscle activity. Then, we investigated whether the differences in target rewards across multiple goals impacted rapid motor decisions during movement. We observed idiosyncratic switching strategies dependent on both target rewards and, surprisingly, the feedback gains at perturbation onset: the more vigorous movements were less likely to switch to a new goal following perturbations. To gain further insight into a c...

The temporal dynamics of perceptual decisions offer a key window into the cognitive processes contributing to decision-making. Investigating perceptual dynamics in a genetically tractable animal model can facilitate the subsequent unpacking of the underlying neural mechanisms. Here, we investigated the time course as well as fundamental psychophysical constants governing visual perceptual decision-making in freely behaving mice. We did so by analyzing response accuracy against reaction time (RT), i.e., conditional accuracy, in a series of two-alternative forced choice (2-AFC) orientation discrimination tasks in which we varied target size, luminance, duration, and presence of a foil. Our results quantified two distinct stages in the time course of mouse visual decision-making: a “sensory encoding” stage in which conditional accuracy exhibits a classic trade-off with response speed, and a subsequent “short-term memory (STM)-dependent” stage in which conditional accuracy exhibits a classic asymptotic decay f...