Neuroligins facilitate the development of bone cancer pain via regulating synaptic transmission: an experimental study.

BACKGROUND: The underlying mechanism of chronic pain involves the plasticity in synaptic receptors and neurotransmitters. This study aimed to investigate potential roles of Neuroligins (NLs) within the spinal dorsal horn of rats in a newly established Bone Cancer Pain (BCP) model. The objective was to explore the mechanism of neuroligin involved in the occurrence and development of bone cancer pain. METHODS: Using our rat BCP model, we assessed pain hypersensitivity over time. Quantitative real-time polymerase chain reaction and Western blot analysis were performed to investigate NL expression, and NLs were overexpressed in the rat spinal cord using lentiviral vectors. Immunofluorescence staining and whole-cell patch-clamp recordings were deployed to investigate the role of NLs in the development of BCP. RESULTS: We observed reduced expression levels of NL1 and NL2, but not of NL3, within the rat spinal cord, which were found to be associated with and essential for the development of BCP in our model. Accordingly, NL1 or NL2 overexpression in the spinal cord alleviated mechanical hypersensitivity of rats. Electrophysiological experiments indicated that NL1 and NL2 are involved in BCP via regulating γ-aminobutyric acid-ergic interneuronal synapses and the activity of glutamatergic interneuronal synapses, respectively. CONCLUSIONS: Our observations unravel the role of NLs in cancer-related chronic pain and further suggest that inhibitory mechanisms are central features of BCP in the spinal dorsal horn. These results provide a new perspective and basis for subsequent studies elucidating the onset and progression of BCP.

How does the use of simultaneous contrast illusion on product-background color combination nudge consumer behavior? A behavioral and event-related potential study.

Color, as one of the most critical visual factors influencing consumer decisions, has been widely used in e-commerce marketing. However, the effects of product-background saturation combination on consumers' willingness to purchase products with different heaviness attributes (e.g., heaviness-positive products or heaviness-negative products) have not been conclusively determined. The current study demonstrated the effects of product-background saturation combination on product heaviness perception and its downstream consequences. Based on behavioral method, study 1 showed that a patch of color placed in a pale background (the saturation of the background is lower than the saturation of the color patch) was perceived as visually heavier than that in a colorful background (the saturation of the background is higher than the saturation of the color patch). Study 2 applied event-related potentials (ERPs) method to explore the underlying neural mechanisms of how the interactions between the presentation modes and the product types affect consumer decisions. Behaviorally, compared to the colorful background, the pale background would lead to a higher purchase rate for the heaviness-positive products, whereas the opposite results were found for the heaviness-negative products. Furthermore, for both the heaviness-positive and heaviness-negative products, a shorter reaction time would be observed in the pale background condition than in the colorful background condition. Neurophysiologically, the pale background would result in smaller N2 component and larger P3 component compared to the colorful background for the heaviness-positive products, while the reverse held for the heaviness-negative products. Smaller N2 component implies decreased perceptual conflicts and larger P3 component implies increased decision confidence, suggesting that e-retailers should present heaviness-positive products with pale backgrounds and heaviness-negative products with colorful backgrounds.

Corrigendum: To Each Their Own: The Impact of Regulatory Focus on Consumers' Response to Online Information Load.

[This corrects the article DOI: 10.3389/fnins.2022.757316.].

To Each Their Own: The Impact of Regulatory Focus on Consumers' Response to Online Information Load.

Contrary to the common view that more information is always better, too much information can damage decision quality. Building on existing literature, this study identified regulatory focus as a critical factor influencing the effect of information load (IL) on online consumer decisions and used event-related potentials (ERPs) to uncover its underlying neural mechanism. Behavioral data showed that promotion-focused participants would spend less time making purchasing decisions in the low IL condition than in the high IL condition. However, no significant difference was found for prevention-focused participants. In contrast to the high IL condition, ERP data indicated that the low IL condition recruited more attentional resources at the early stage of rapid automated processing (larger P2 component), leading to reduced long-term memory conflict (smaller N2 component), and resulting in enhanced decision confidence (larger P3 component) for those with a promotion focus. However, we observed either weakened or even opposite outcomes for those with a prevention focus. These findings generally shed light on when e-retailers should provide large/small amounts of product information in online environments.

NWD1 facilitates synaptic transmission and contributes to neuropathic pain.

Neuropathic pain is the most common symptom for which patients seek medical attention. Existing treatments to control pain are largely ineffective because of poor understanding the underlying mechanisms. Synaptic plasticity is fundamental to the spinal sensitivity of neuropathic pain. In the present study, we showed that SNL induced significant allodynia and hyperalgesia as well as upregulation of Nwd1 and GluN2B, which were reversed by knockdown of NWD1. Electrophysiological experiments demonstrated that SNL enhanced synaptic transmission, which was prevented by knockdown of NWD1. In vitro experiments showed that knockdown of NWD1 inhibited dendritic growth and synaptogenesis. Taken together, our results suggest that NWD1 enhances synaptic transmission and contributes to the development of neuropathic pain by enhancing GluN2B synaptic expression and anchor and promoting excitatory synaptogenesis.

How Does Information Overload Affect Consumers' Online Decision Process? An Event-Related Potentials Study.

One of the advantages of e-retailers is their capability to provide a large amount of information to consumers. However, when the amount of information exceeds consumers' information processing capacities, it will lead to worse decision quality and experience, causing the information overload effect. In this study, the event-related potentials (ERPs) were applied to examine the hidden neural mechanism of the impact of information overload on consumers' decision processes. Behavioral data showed that people would spend more time making decisions when faced with information overload. Neurophysiologically, consumers would invest less attentional resources in the high amount of information (HAI) condition than those in the low amount of information (LAI) condition and lead to less positive P2 amplitudes. The HAI condition would increase decision difficulty than would the LAI condition and result in smaller P3 amplitudes. In addition, an increased late positive component (LPC) was observed for the HAI condition in contrast to the LAI condition, indicating that consumers were more inclined to have decision process regret when consumers were overloaded. We further investigated the dynamic information processing when consumers got over information overload by mining the brain's time-varying networks. The results revealed that during the decision process and the neural response stage, the central area controlled other brain regions' activities for the HAI condition, suggesting that people may still consider and compare other important information after the decision process when faced with information overload. In general, this study may provide neural evidence of how information overload affects consumers' decision processes and ultimately damages decision quality.

Electrophysiological Properties of Substantia Gelatinosa Neurons in the Preparation of a Slice of Middle-Aged Rat Spinal Cord.

A patch-clamp recording in slices generated from the brain or the spinal cord has facilitated the exploration of neuronal circuits and the molecular mechanisms underlying neurological disorders. However, the rodents that are used to generate the spinal cord slices in previous studies involving a patch-clamp recording have been limited to those in the juvenile or adolescent stage. Here, we applied an N-methyl-D-glucamine HCl (NMDG-HCl) solution that enabled the patch-clamp recordings to be performed on the superficial dorsal horn neurons in the slices derived from middle-aged rats. The success rate of stable recordings from substantia gelatinosa (SG) neurons was 34.6% (90/260). When stimulated with long current pulses, 43.3% (39/90) of the neurons presented a tonic-firing pattern, which was considered to represent γ-aminobutyric acid-ergic (GABAergic) signals. Presumptive glutamatergic neurons presented 38.9% (35/90) delayed and 8.3% (7/90) single-spike patterns. The intrinsic membrane properties of both the neuron types were similar but delayed (glutamatergic) neurons appeared to be more excitable as indicated by the decreased latency and rheobase values of the action potential compared with those of tonic (GABAergic) neurons. Furthermore, the glutamatergic neurons were integrated, which receive more excitatory synaptic transmission. We demonstrated that the NMDG-HCl cutting solution could be used to prepare the spinal cord slices of middle-aged rodents for the patch-clamp recording. In combination with other techniques, this preparation method might permit the further study of the functions of the spinal cord in the pathological processes that occur in aging-associated diseases.

CXCL12 promotes spinal nerve regeneration and functional recovery after spinal cord injury.

Spinal cord injury (SCI) leads to permanent loss of motor and sensory function due to the complex mechanisms of the external microenvironment and internal neurobiochemistry that restrict neuronal plasticity and axonal regeneration. Chemokine CXCL12 was verified in regulating the development of central nervous system (CNS) and repairing of CNS disease. In the present study, CXCL12 was downregulated in the spinal cord after SCI. SCI also induced gliosis and loss of synapse. Intrathecal treatment of CXCL12 promoted the functional recovery of SCI by inducing the formation of neuronal connections and suppressing glia scar. To confirm whether CXCL12 promoted synapse formation and functional neuronal connections, the primary cortical neurons were treated with CXCL12 peptide, the synapse was examined using Immunofluorescence staining and the function of synapse was tested using a whole-cell patch clamp. The results indicated that CXCL12 peptide promoted axonal elongation, branche formation, dendrite generation and synaptogenesis. The electrophysiological results showed that CXCL12 peptide increased functional connections among neurons. Taken together, the present study illustrated an underlying mechanism of the development of SCI and indicated a potential approach to facilitate functional recovery of spinal cord after SCI.