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 with non-native English speakers on most measures, and that lexical processing was reduced by the visual task. Moreov...

In 1987, while investigating the iap gene in Escherichia coli , Nakata and colleagues identified “five highly homologous sequences of 29 nucleotides were arranged as direct repeats with 32 nucleotides as spacing.” Perplexed by this discovery, the authors stated, “so far, no sequence homologous to these has been found elsewhere in prokaryotes, and the biological significance of these sequences is not known.” These few sentences launched a decades-long investigation into the biological mystery of clustered regularly interspaced short palindromic repeats, or CRISPR (Ishino et al., 1987). Since its first identification, CRISPR—an adaptive immune response in prokaryotic organisms to recognize and combat infectious DNA—has been developed into a tool for targeted gene editing in a variety of cells and organisms (Jansen et al., 2002). The utility of CRISPR lies in the easy targeting of virtually any genomic location by a short RNA guide. In its simplest form, the two components that must be expressed in cells to ...

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 males and 8 females) 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 i...

Recent neurophysiological studies provide inconsistent results of frontoparietal network (FPN) stimulation for altering working memory (WM) capacity. This study aimed to boost WM capacity by manipulating the activity of the FPN via dual-site high–definition transcranial direct current stimulation. Forty-eight participants were randomly assigned to three stimulation groups, receiving either simultaneous anodal stimulation of the frontal and parietal areas (double stimulation), or stimulation of the frontal area only (single stimulation), or the placebo stimulation (sham) to frontal and parietal areas. After the stimulation, we used an operation span task to test memory accuracy, mathematical accuracy, time of calculation and memorizing, and recall response time across the three groups. The results revealed an enhancement of memory accuracy and a reduction of time of calculation in the double stimulation group compared with that in others. In addition, recall response time was significantly decreased in the ...

The external part of the globus pallidus (GPe) is pivotal for the regulation, processing, and control of information within the basal ganglia (BG) network. The GPe is extensively interconnected with the striatum, the subthalamic nucleus, and the internal globus pallidus, forming intricate feedback and feedforward loops. The GPe is primarily composed of two types of GABAergic neural populations, known as arkypallidal and prototypic neurons. Prototypic neurons, the most numerous among these neurons, exhibit high-frequency autonomous spiking activity (30–60 Hz). Under healthy conditions, this activity is largely asynchronous, which is often interpreted as indicative of independent and parallel processing channels within the BG network. The increase of synchronization in the neural activity of the BG, particularly within the beta frequency range, is significantly associated with the progression of Parkinson's disease (PD; Nini et al., 1995). Over the past two decades, substantial evidence has emphasized the c...

Episodic memory, the ability to recall specific events and experiences, is a cornerstone of human cognition with profound clinical implications. While animal studies have provided valuable insights into the neuronal underpinnings of episodic memory, research has largely relied on a limited subset of tasks that model only some aspects of episodic memory. In this narrative review, we provide an overview of rodent episodic-like memory tasks that expand the methodological repertoire and diversify the approaches used in episodic-like memory research. These tasks assess various aspects of human episodic memory, such as integrated what–where–when or what–where memory , source memory, free recall, temporal binding, and threshold retrieval dynamics. We review each task’s general principle and consider whether alternative non-episodic mechanisms can account for the observed behavior. While our list of tasks is not exhaustive, we hope it will guide researchers in selecting models that align with their specific resear...

Uncovering the relationships between neural circuits, behavior, and neural dysfunction may require rodent pose tracking. While open-source toolkits such as DeepLabCut have revolutionized markerless pose estimation using deep neural networks, the training process still requires human intervention for annotating key points of interest in video data. To further reduce human labor for neural network training, we developed a method that automatically generates annotated image datasets of rodent paw placement in a laboratory setting. It uses invisible but fluorescent markers that become temporarily visible under UV light. Through stroboscopic alternating illumination, adjacent video frames taken at 720 Hz are either UV or white light illuminated. After color filtering the UV-exposed video frames, the UV markings are identified and the paw locations are deterministically mapped. This paw information is then transferred to automatically annotate paw positions in the next white light-exposed frame that is later use...

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...

Volatile anesthetics are currently believed to cause unconsciousness by acting on one or more molecular targets including neural ion channels, receptors, mitochondria, synaptic proteins, and cytoskeletal proteins. Anesthetic gases including isoflurane bind to cytoskeletal microtubules (MTs) and dampen their quantum optical effects, potentially contributing to causing unconsciousness. This possibility is supported by the finding that taxane chemotherapy consisting of MT-stabilizing drugs reduces the effectiveness of anesthesia during surgery in human cancer patients. In order to experimentally assess the contribution of MTs as functionally relevant targets of volatile anesthetics, we measured latencies to loss of righting reflex (LORR) under 4% isoflurane in male rats injected subcutaneously with vehicle or 0.75 mg/kg of the brain-penetrant MT–stabilizing drug epothilone B (epoB). EpoB-treated rats took an average of 69 s longer to become unconscious as measured by latency to LORR. This was a statistically ...

Older listeners often report difficulties understanding speech in noisy environments. It is important to identify where in the auditory pathway hearing-in-noise deficits arise to develop appropriate therapies. We tested how encoding of sounds is affected by masking noise at early stages of the auditory pathway by recording responses of principal cells in the anteroventral cochlear nucleus (AVCN) of aging CBA/CaJ and C57BL/6J mice in vivo. Previous work indicated that masking noise shifts the dynamic range of single auditory nerve fibers (ANFs), leading to elevated tone thresholds. We hypothesized that such threshold shifts could contribute to increased hearing-in-noise deficits with age if susceptibility to masking increased in AVCN units. We tested this by recording the responses of AVCN principal neurons to tones in the presence and absence of masking noise. Surprisingly, we found that masker-induced threshold shifts decreased with age in primary-like units and did not change in choppers. In addition, sp...