European Journal of Neuroscience最新文献

The glutamate delta 1 receptor (GluD1) remained largely unexplored since its cloning three decades ago because it lacked typical ligand-gated ion channel activity. In the last decade, much progress has been made in identifying its potential function. This research has been greatly enhanced by the development of specific tools to determine receptor expression and distribution and genetic mouse models to explore region specific roles in regulating circuits and behavior. Major strides have also been taken in understanding the structure–function of the receptor. These studies demonstrate that GluD1 has many distinctive characteristics including synaptogenic activity at both excitatory and inhibitory synapses, the ability of the ligand-binding domain to bind not only D-serine but also GABA, its unique structural arrangement among the ionotropic glutamate receptor family in relation to domain swapping and the ability to induce tonic currents in the native system. Studies have also identified its role in regulating the postsynaptic content of AMPA and NMDA receptors and synaptic plasticity. Finally, human genetic studies revealed the relationship of GluD1 with neuropsychiatric disorders, including schizoaffective disorders and intellectual disability, which is consistent with the phenotypes observed in mice upon GluD1 ablation. The role of GluD1 is also becoming evident in neurological disorders, particularly chronic pain. Thus, GluD1 has quickly emerged as a receptor with multifaceted roles in physiology and pathology.

The proper interpretation of environmental information is necessary for effective decision-making. The resulting cognitive burden may affect the entire process if interpretation is not instantaneous. In this study, we investigated how numerical distance (ND), a measure of cognitive demand in numerical comparisons, influences movement initiation and inhibition. To this end, 32 participants completed a novel numerical comparison stop-signal task (NC-SST), in which the cognitive demand of each trial was manipulated by varying the ND between pairs of numbers presented in both Go and Stop signals. Participants were required to initiate or stop a movement if the number was higher or smaller than the one indicated as reference. Results showed that larger NDs (i.e., easier comparisons) facilitated faster and more accurate responses during movement initiation and enhanced stopping performance. Using a generalized drift-diffusion model, we found that drift rates increased with Go ND and were modulated by the spatial location of numerical stimuli, consistent with a left-to-right space number association. A generalized linear mixed-effects model further revealed that Go process parameters, particularly the drift rate, strongly predicted successful stopping and interacted with Stop ND and stop-signal delay (SSD). These findings demonstrate that greater cognitive difficulty impairs both movement initiation and inhibition, and that motor decisions result from the integration of cognitive information onto perceptual features, extending the classical race model framework.

This study examined the effect of brain hemisphere stimulation on effort intensity. We applied high-definition transcranial direct current stimulation (HD-tDCS) to the dorsolateral prefrontal cortex (dlPFC) to manipulate left or right hemispheric activity and assess its impact on cardiovascular responses reflecting effort. In total, 102 participants (65 women, 37 men) performed a mental concentration task under right cathodal, left cathodal, or sham stimulation conditions. We recorded cardiovascular responses, including pre-ejection period (PEP), systolic blood pressure (SBP), heart rate (HR), and diastolic blood pressure (DBP). Preregistered hypotheses predicted right cathodal stimulation to lead to greater left frontal hemispheric activity. This should result in higher effort during a mental concentration task of unclear difficulty by increasing approach motivation and thus success importance. As predicted, right cathodal stimulation increased PEP and SBP reactivity, indicating higher effort compared to the left cathodal and sham stimulation conditions. However, this effect was only evident in women, with men exhibiting a contrasting pattern. Our findings highlight the sex-specific effects of brain stimulation on cardiovascular responses reflecting effort, with the anticipated effects appearing in women.

G-protein coupled receptor (GPCR) 75 (GPR75) is a 540 amino acid member of the G_αq class of GPCRs, with no homology with other classic GPCRs. The current focus on GPR75 has centred on its potential role in metabolic disorders and cancer. GPR75 expression is abundant in the central nervous system (CNS) more so than in the peripheral tissues; however, much remains unknown about the distribution and role of this receptor throughout the CNS. In this study, we quantified GPR75 mRNA expression in the mouse CNS using RNAscope fluorescent in situ hybridization (FISH) technology, combined with immunohistochemistry (IHC) to detect GPR75 transcripts in specific neuronal cell types. GPR75 knockout (KO) mice were used as controls and specificity of hybridization. Our results show that GPR75 mRNA expression occurs in several neuronal populations including GABAergic and glutamatergic neurons. In select areas, such as the substantia nigra/ventral tegmental area, locus coeruleus and raphe nucleus, GPR75 mRNA is also highly expressed in monoaminergic neurons. Moreover, we found high expression of GPR75 mRNA in the cerebellum, in both GABAergic and glutamatergic neurons, suggesting a potential role for this receptor in motor/equilibrium activity. Indeed, GPR75 KO mice perform significantly better than wild-type littermates on the rotarod test. Our data suggest that this receptor may play an important role in brain physiology and function.

The relationship between primary (S1) and secondary (S2) somatosensory cortex is not well understood, and the role of S2 in somatosensory function is not well defined. To test the role of S2 and its interplay with S1 in learning a texture discrimination, we reversibly inhibited primary (S1) and/or secondary somatosensory cortex (S2) bilaterally using DREADDs and measured the effect on the ability of mice to learn a whisker-dependent tactile discrimination. Freely moving mice foraged in an arena that contained two bowls, one of which contained a buried food reward. The bowls could only be distinguished by the texture on the outer surface. DREADD-mediated inhibition suppressed sensory responses and disrupted network activity in the cortical area in which DREADDs were expressed. We found that both S1 and S2 were critical for learning the tactile discrimination. Tactile learning in naive mice required normal S2 function during the learning phase but not during the post-training consolidation phase of approximately 6 h. Furthermore, S2 was only required during learning. Once expert levels of discrimination had been attained, S2 was not required for execution of the learned discrimination. The role of S2 was confined to tactile learning and was not required for olfactory discrimination. Our findings suggest that S1 and S2 interact when learning a new tactile discrimination, but the learned skill eventually becomes independent of S2.

Tsetse flies (Glossina sp.) are important disease vectors with unique biology that makes them fascinating models to study the evolution of behaviour and its underlying neural circuits. They evolved blood-feeding in an independent event from mosquitoes, and unlike most insects, give birth to a single live offspring—rather than laying eggs. Given their impact on public health, they have been extensively studied with a strong focus on vector control. However, information on their sensory ecology and neurobiology is thinly spread across the literature. Here, we review over a hundred years of literature on tsetse sensory systems, including olfaction, vision, audition, taste, thermosensation and mechanosensation, in the context of the behaviours they drive, including host-finding, blood-feeding and mating. We embed the available data within our more detailed understanding of the sensory systems of the vinegar fly Drosophila melanogaster and other diptera. This sets the stage for future work on how tsetse find their hosts and reproduce, opening new avenues to understand how their sensory systems function and evolve, which in turn will inform better control strategies to reduce the burden of the diseases they transmit.

Uncertainty is a key contributor to decision making, and humans show inconsistent attitudes towards it. Although excessive uncertainty-avoidance or uncertainty-seeking are hallmark symptoms of several mental conditions, the neural mechanism underlying uncertainty seeking and avoidance remains unclear. Here, we probed whether changes in pupil-linked arousal are indicative of uncertainty avoidance in humans. Investigating baseline pupil size to capture endogenous fluctuations across two experiments (N₁ = 24, N₂ = 21), we found that pretrial pupillary responses (as early as 700 ms prior to the onset of a trial) were closely related to uncertainty attitudes during multiarmed bandit tasks. Although increased baseline pupil size signalled avoidance in uncertainty-related decisions, it did not foreshadow value processing per se. The specificity of our results suggests that uncertainty processing is dynamic and depends on (potentially noradrenergic) endogenous pupil fluctuations.