Presynaptic Enhancement of Transmission from Nociceptors Expressing Nav1.8 onto Lamina-I Spinothalamic Tract Neurons by Spared Nerve Injury in Mice.

Alteration of synaptic function in the dorsal horn (DH) has been implicated as a cellular substrate for the development of neuropathic pain, but certain details remain unclear. In particular, the lack of information on the types of synapses that undergo functional changes hinders the understanding of disease pathogenesis from a synaptic plasticity perspective. Here, we addressed this issue by using optogenetic and retrograde tracing ex vivo to selectively stimulate first-order nociceptors expressing Nav1.8 (NRsNav1.8) and record the responses of spinothalamic tract neurons in spinal lamina I (L1-STTNs). We found that spared nerve injury (SNI) increased excitatory postsynaptic currents (EPSCs) in L1-STTNs evoked by photostimulation of NRsNav1.8 (referred to as Nav1.8-STTN EPSCs). This effect was accompanied by a significant change in the failure rate and paired-pulse ratio of synaptic transmission from NRsNav1.8 to L1-STTN and in the frequency (not amplitude) of spontaneous EPSCs recorded in L1-STTNs. However, no change was observed in the ratio of AMPA to NMDA receptor-mediated components of Nav1.8-STTN EPSCs or in the amplitude of unitary EPSCs constituting Nav1.8-STTN EPSCs recorded with extracellular Ca2+ replaced by Sr2+ In addition, there was a small increase (approximately 10%) in the number of L1-STTNs showing immunoreactivity for phosphorylated extracellular signal-regulated kinases in mice after SNI compared with sham. Similarly, only a small percentage of L1-STTNs showed a lower action potential threshold after SNI. In conclusion, our results show that SNI induces presynaptic modulation at NRNav1.8 (consisting of both peptidergic and nonpeptidergic nociceptors) synapses on L1-STTNs forming the lateral spinothalamic tract.

Pupillary Responses Reflect Dynamic Changes in Multiple Cognitive Factors During Associative Learning in Primates.

Associative learning involves complex interactions of multiple cognitive factors. While adult subjects can articulate these factors verbally, for model animals such as macaques, we rely on behavioral outputs. In our study, we used pupillary responses as an alternative measure to capture these underlying cognitive changes. We recorded the dynamic changes in the pupils of three male macaques when they learned the associations between visual stimuli and reward sizes under the classical Pavlovian experimental paradigm. We found that during the long-term learning process, the gradual changes in the pupillary response reflect the changes in the cognitive state of the animals. The pupillary response can be explained by a linear combination of components corresponding to multiple cognitive factors. These components reflect the impact of visual stimuli on the pupils, the prediction of reward values associated with the visual stimuli, and the macaques' understanding of the current experimental reward rules. The changing patterns of these factors during interday and intraday learning clearly demonstrate the enhancement of current reward-stimulus association and the weakening of previous reward-stimulus association. Our study shows that the dynamic response of pupils can serve as an objective indicator to characterize the psychological changes of animals, understand their learning process, and provide important tools for exploring animal behavior during the learning process.

Hostile Attribution Bias Shapes Neural Synchrony in the Left Ventromedial Prefrontal Cortex during Ambiguous Social Narratives.

Hostile attribution bias refers to the tendency to interpret social situations as intentionally hostile. While previous research has focused on its developmental origins and behavioral consequences, the underlying neural mechanisms remain underexplored. Here, we employed functional near-infrared spectroscopy (fNIRS) to investigate the neural correlates of hostile attribution bias. While undergoing fNIRS, male and female participants listened to and provided attribution ratings for 21 hypothetical scenarios where a character's actions resulted in a negative outcome for the listener. Ratings of hostile intentions were averaged to measure hostile attribution bias. Using intersubject representational similarity analysis, we found that participants with similar levels of hostile attribution bias exhibited higher levels of neural synchrony during narrative listening, suggesting shared interpretations of the scenarios. This effect was localized to the left ventromedial prefrontal cortex (VMPFC) and was particularly prominent in scenarios where the character's intentions were highly ambiguous. We then grouped participants into high and low bias groups based on a median split of their hostile attribution bias scores. A similarity-based classifier trained on the neural data classified participants as having high or low bias with 75% accuracy, indicating that the neural time courses during narrative listening was systematically different between the two groups. Furthermore, hostile attribution bias correlated negatively with attributional complexity, a measure of one's tendency to consider multifaceted causes when explaining behavior. Our study sheds light on the neural mechanisms underlying hostile attribution bias and highlights the potential of using fNIRS to develop nonintrusive and cost-effective neural markers of this sociocognitive bias.