Li Yang

Cooperation is a fundamental form of social behavior that promotes collective benefits and group survival. Although considerable progress has been made in understanding cooperation from behavioral and theoretical perspectives, the neural activities underlying cooperative behavior remain incompletely understood. In the present study, we established a cooperative behavioral paradigm in pairs of mice using a Skinner box, with the protocol spanning 22 days. Mice were retrospectively classified into high-, middle-, and low-performance groups based on their performance in the cooperation task. In vivo local field potential recordings from the nucleus accumbens and ventral hippocampus were then conducted in the three groups. High-cooperation mice showed significantly increased delta and low-gamma power in the nucleus accumbens, as well as enhanced delta, theta, beta, and low-gamma power in the ventral hippocampus, compared to low-cooperation mice. Meanwhile, nucleus accumbens–ventral hippocampus coherence within the beta and low-gamma frequency bands was significantly reduced in high-cooperation animals. Behaviorally, high-cooperation mice exhibited social dysfunction as shown by reduced social interaction and more pronounced anxiety-like behaviors compared with low-cooperation mice after training. Collectively, these findings provide early evidence that individual differences in cooperative behavior are associated with distinct patterns of neural oscillatory activity within the nucleus accumbens–ventral hippocampus circuit. Moreover, enhanced cooperative performance was correlated with alterations in social and affective behavior, such as increased social avoidance and anxiety-like behavior. The results suggest that nucleus accumbens–ventral hippocampus oscillatory dynamics may represent a neural correlate of cooperative behavior, and that training-induced differences in cooperative performance are associated with subsequent changes in social and affective functioning.

Cleavage of amyloid precursor protein (APP) produces toxic amyloid-beta peptides, which play a critical role in the pathogenesis of Alzheimer's disease. Neuronal loss is a key feature of Alzheimer's disease. Despite the importance of APP in the proliferation of neural progenitors and the survival of adult-born granule cells in the dentate gyrus, little is known about the effect of APP deficiency on neuronal electrophysiological activities and the survival of newly born neurons. Utilizing whole-cell patch-clamp recording in combination with retroviral labeling and immunofluorescent staining in Alzheimer's disease model mice with App knockout (App-/-), we show that APP deficiency increased the number of adult-born granule cells at 4 weeks post-injection, but did not affect their intrinsic excitability or miniature current activity. In contrast, at 10 weeks post-injection, adult-born granule cells showed increased abundance and intrinsic excitability that were associated with abnormal dendritic morphology, increased miniature excitatory- and inhibitory-synaptic transmission, and decreased potassium-chloride-cotransporter 2 expression. Compared with adult-born granule cells at 10 week post-injection, mature granule cells exhibited decreased intrinsic excitability and potassium-chloride-cotransporter 2 expression alongside increased apoptosis in App-/- mice. Additionally, although App-/-mice showed abnormal freezing behavior and elevated mature granule cell activation during contextual fear conditioning, adult-born granule cells were not recruited in either App-/- or wild-type control mice. Taken together, these findings suggest that APP is required for adult-born granule cell maturation and that APP deficiency induces excitotoxicity in adult-born granule cells at 10 weeks post-injection, promoting subsequent apoptosis of mature granule cells.

Microglia are resident immune cells in the brain that interact with neurons to maintain the homeostasis of the central nervous system (CNS). Studies show ...

Microglia are resident immune cells in the brain that interact with neurons to maintain the homeostasis of the central nervous system (CNS). Studies show ...

JOURNAL/nrgr/04.03/01300535-202511000-00029/figure1/v/2026-04-24T022020Z/r/image-tiff Neuronal activity, synaptic transmission, and molecular changes in the basolateral amygdala play critical roles in fear memory. Cylindromatosis (CYLD) is a deubiquitinase that negatively regulates the nuclear factor kappa-B pathway. CYLD is well studied in non-neuronal cells, yet under-investigated in the brain, where it is highly expressed. Emerging studies have shown involvement of CYLD in the remodeling of glutamatergic synapses, neuroinflammation, fear memory, and anxiety- and autism-like behaviors. However, the precise role of CYLD in glutamatergic neurons is largely unknown. Here, we first proposed involvement of CYLD in cued fear expression. We next constructed transgenic model mice with specific deletion of Cyld from glutamatergic neurons. Our results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male mice. Further, loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation, impaired excitatory synaptic transmission, and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male mice. Altogether, our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal, synaptic, and microglial activation. This may contribute, at least in part, to cued fear expression.

It is known that humans and rodents are capable of transmitting stress to their naive partners via social interaction. However, a comprehensive understanding of transmitted stress, which may differ from authentic stress, thus revealing unique neural mechanisms of social interaction resulting from transmitted stress and the associated anxiety, is missing. We used, in the present study, maternal separation (MS) as a stress model to investigate whether MS causes abnormal behavior in adolescence. A key concern in the analysis of stress transmission is whether the littermates of MS mice who only witness MS stress (“Partners”) exhibit behavioral abnormalities similar to those of MS mice themselves. Of special interest is the establishment of the neural mechanisms underlying transmitted stress and authentic stress. The results show that Partners, similar to MS mice, exhibit anxiety-like behavior and hyperalgesia after witnessing littermates being subjected to early-life repetitive MS. Electrophysiological analysis revealed that mice subjected to MS demonstrate a reduction in both the excitatory and inhibitory synaptic activities of parvalbumin interneurons (PVINs) in the anterior cingulate cortex (ACC). However, Partners differed from MS mice in showing an increase in the number and excitability of GABAergic PVINs in the ACC and in the ability of chemogenetic PVIN inactivation to eliminate abnormal behavior. Furthermore, the social transfer of anxiety-like behavior required intact olfactory, but not visual, perception. This study suggests a functional involvement of ACC PVINs in mediating the distinct neural basis of transmitted anxiety. SIGNIFICANCE STATEMENT The anterior cingulate cortex (ACC) is a critical brain area in physical and social pain and contributes to the exhibition of abnormal behavior. ACC glutamatergic neurons have been shown to encode transmitted stress, but it remains unclear whether inhibitory ACC neurons also play a role. We evaluate, in this study, ACC neuronal, synaptic and network activities and uncover a critical role of parvalbumin interneurons (PVINs) in the expression of transmitted stress in adolescent mice who had witnessed MS of littermates in infancy. Furthermore, inactivation of ACC PVINs blocks transmitted stress. The results suggest that emotional contagion has a severe effect on brain function, and identify a potential target for the treatment of transmitted anxiety.

JOURNAL/nrgr/04.03/01300535-202406000-00040/inline-graphic1/v/2025-09-25T172020Z/r/image-tiff Tibetan singing bowls emit low-frequency sounds and produce perceptible harmonic tones and vibrations through manual tapping. The sounds the singing bowls produce have been shown to enhance relaxation and reduce anxiety. However, the underlying mechanism remains unclear. In this study, we used chronic restraint stress or sleep deprivation to establish mouse models of anxiety that exhibit anxiety-like behaviors. We then supplied treatment with singing bowls in a bottomless cage placed on the top of a cushion. We found that unlike in humans, the combination of harmonic tones and vibrations did not improve anxiety-like behaviors in mice, while individual vibration components did. Additionally, the vibration of singing bowls increased the level of N-methyl-D-aspartate receptor 1 in the somatosensory cortex and prefrontal cortex of the mice, decreased the level of γ-aminobutyric acid A (GABA) receptor α 1 subtype, reduced the level of CaMKII in the prefrontal cortex, and increased the number of GABAergic interneurons. At the same time, electrophysiological tests showed that the vibration of singing bowls significantly reduced the abnormal low-frequency gamma oscillation peak frequency in the medial prefrontal cortex caused by stress restraint pressure and sleep deprivation. Results from this study indicate that the vibration of singing bowls can alleviate anxiety-like behaviors by reducing abnormal molecular and electrophysiological events in somatosensory and medial prefrontal cortex.

Biocytin, a chemical compound that is an amide formed from the vitamin biotin and the amino acid L-lysine, has been used as a histological dye to stain nerve cells. Electrophysiological activity and morphology are two key characteristics of neurons, but revealing both the electrophysiological and morphological properties of the same neuron is challenging. This article introduces a detailed and easy-to-operate procedure for single-cell labeling in combination with whole-cell patch-clamp recording. Using a recording electrode filled with a biocytin-containing internal solution, we demonstrate the electrophysiological and morphological characteristics of pyramidal (PNs), medial spiny (MSNs) and parvalbumin neurons (PVs) in brain slices, where the electrophysiological and morphological properties of the same individual cell are elucidated. We first introduce a protocol for whole-cell patch-clamp recording in various neurons, coupled with the intracellular diffusion of biocytin delivered by the glass capillary of the recording electrode, followed by a post hoc procedure to reveal the architecture and morphology of biocytin-labeled neurons. An analysis of action potentials (APs) and neuronal morphology, including the dendritic length, number of intersections, and spine density of biocytin-labeled neurons, were performed using ClampFit and Fiji Image (ImageJ), respectively. Next, to take advantage of the techniques introduced above, we uncovered defects in the APs and the dendritic spines of PNs in the primary motor cortex (M1) of deubiquitinase cylindromatosis (CYLD) knock-out (Cyld^−/−) mice. In summary, this article provides a detailed methodology for revealing the morphology as well as the electrophysiological activity of a single neuron that will have many applications in neurobiology.

Corrigendum: Neural mechanism underlies CYLD modulation of morphology and synaptic function of medium spiny neurons in dorsolateral striatum