Comorbid chronic neuropathic pain and anxiety is a common disease that represents a major clinical challenge. The underlying mechanisms of chronic neuropathic pain and anxiety are not entirely understood, which limits the exploration of effective treatment methods. Glutamatergic neurons in the ventrolateral periaqueductal gray (vlPAG) have been implicated in regulating pain, but the potential roles of the vlPAG in neuropathic pain-induced anxiety have not been investigated. Herein, whole-cell recording and immunofluorescence showed that the excitability of CamkIIα neurons in the vlPAG (vlPAGCamkIIα+ neurons) was decreased in mice with spared nerve injury (SNI), while electroacupuncture (EA) activated these neurons. We also showed that chemogenetic inhibition of vlPAGCamkIIα+ neurons resulted in allodynia and anxiety-like behaviors in naive mice. Furthermore, chemogenetic activation of vlPAGCamkIIα+ neurons reduced anxiety-like behaviors and allodynia in mice with SNI, and EA had a similar effect in allevia...

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 ...

Language is an evolutionarily salient faculty for humans that relies on a distributed brain network spanning across frontal, temporal, parietal, and subcortical regions. To understand whether the complex language network shares common or distinct genetic mechanisms, we examined the relationships between the genetic effects underlying the brain responses to language and a set of object domains that have been suggested to coevolve with language: tools, faces (indicating social), and body parts (indicating social and gesturing). Analyzing the twin datasets released by the Human Connectome Project that had functional magnetic resonance imaging data from human twin subjects (monozygotic and dizygotic) undergoing language and working memory tasks contrasting multiple object domains (198 females and 144 males for the language task; 192 females and 142 males for the working memory task), we identified a set of cortical regions in the frontal and temporal cortices and subcortical regions whose activity to language ...

Cognitive dysfunction is associated with methamphetamine use disorder (MUD). Here, we used genetic and pharmacological approaches to examine the involvement of either Group 2 metabotropic glutamate (mGlu2) or mGlu3 receptors in memory deficit induced by methamphetamine in mice. Methamphetamine treatment (1 mg/kg, i.p., once a day for 5 d followed by 7 d of withdrawal) caused an impaired performance in the novel object recognition test in wild-type mice, but not in mGlu2−/− or mGlu3−/− mice. Memory deficit in wild-type mice challenged with methamphetamine was corrected by systemic treatment with selectively negative allosteric modulators of mGlu2 or mGlu3 receptors (compounds VU6001966 and VU0650786, respectively). Methamphetamine treatment in wild-type mice caused large increases in levels of mGlu2/3 receptors, the Type 3 activator of G-protein signaling (AGS3), Rab3A, and the vesicular glutamate transporter, vGlut1, in the prefrontal cortex (PFC). Methamphetamine did not alter mGlu2/3-mediated inhibition ...

It has long been assumed that activity patterns persist in neuronal circuits after they are first experienced, as part of the process of information processing and storage by the brain. However, these “reverberations” of current activity have not been directly observed on a single-neuron level in a mammalian system. Here we demonstrate that specific induced activity patterns are retained in mature cultured hippocampal neuronal networks. Neurons within the network are induced to fire at a single frequency or in a more complex pattern containing two distinct frequencies. After the stimulation was stopped, the subsequent neuronal activity of hundreds of neurons in the network was monitored. In the case of single-frequency stimulation, it was observed that many of the neurons continue to fire at the same frequency that they were stimulated to fire at. Using a recurrent neural network trained to detect specific, more complex patterns, we found that the multiple-frequency stimulation patterns were also retained ...

While injury responses are generally well studied, the focus tends to be on axon regeneration, leaving dendrite-specific contribution after injury and the regeneration process less understood. After axons are injured, the area distal to the crush site degenerates, and injury signaling is initiated by a retrograde calcium wave that activates stress signaling including dual leucine zipper kinase (DLK)/JNK activation, transcription of regeneration associated genes, and directed local translation which allows ultimately for reinitiation of axon outgrowth. Potential for outgrowth is greater in the peripheral nervous system as compared with that in the central. Dendrites, like axons, are vulnerable to injury from stroke, seizure, and traumatic injury, but limitations in the ability to generate a targeted injury and the inability to track dendrites of individual cells in vertebrate models make the study of dendrite injury and regeneration difficult. Advancements have been made in the use of lasers to induce preci...

Moving effectively is essential for any animal. Thus, many different kinds of brain processes likely contribute to learning and adapting movement. How these contributions are combined is unknown. Nevertheless, the field of motor adaptation has been working under the assumption that measures of explicit and implicit motor adaptation can simply be added in total adaptation. While this has been tested, we show that these tests were insufficient. We put this additivity assumption to the test in various ways and find that measures of implicit and explicit adaptation are not additive. This means that future studies should measure both implicit and explicit adaptation directly. It also challenges us to disentangle how various motor adaptation processes do combine when producing movements and may have implications for our understanding of other kinds of learning as well (data and code: <https://osf.io/3yhw5>).

Adaptive behavior relies on efficient cognitive control. The anterior cingulate cortex (ACC) is a key node within the executive prefrontal network. The reciprocal connectivity between the locus ceruleus (LC) and ACC is thought to support behavioral reorganization triggered by the detection of an unexpected change. We transduced LC neurons with either excitatory or inhibitory chemogenetic receptors in adult male rats and trained rats on a spatial task. Subsequently, we altered LC activity and confronted rats with an unexpected change of reward locations. In a new spatial context, rats with decreased noradrenaline (NA) in the ACC entered unbaited maze arms more persistently which was indicative of perseveration. In contrast, the suppression of the global NA transmission reduced perseveration. Neither chemogenetic manipulation nor inactivation of the ACC by muscimol affected the rate of learning, possibly due to partial virus transduction of the LC neurons and/or the compensatory engagement of other prefronta...

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 ...