European Journal of Neuroscience最新文献

Freezing of gait (FoG) is a disabling motor symptom in Parkinson's disease (PD) characterized by brief episodes of inability to step, often triggered by cognitive-motor conflict. Step initiation (SI) involves anticipatory postural adjustments (APAs), which are critical for balance and movement preparation. This study aimed to investigate the neural and biomechanical correlates of FoG during SI under congruent and incongruent conditions, focusing on the supplementary motor area (SMA) and dorsolateral prefrontal cortex (DLPFC), regions associated with motor preparation and inhibitory control. Thirty-three individuals with PD (15 with FoG and 18 without FoG) performed a stepping initiation task under two conditions: congruent (aligned visual cues) and incongruent (conflicting visual cues). APAs were analyzed using biomechanical data, while functional near-infrared spectroscopy measured oxyhemoglobin (oxy-Hb) concentrations in the SMA and DLPFC. Two-way ANOVA assessed differences between groups and conditions. Incongruent conditions resulted in higher APA amplitude, duration, delay, and task error rates than congruent conditions. Individuals with FoG exhibited reduced SMA activation compared to those without FoG, particularly during incongruent tasks. DLPFC activation was greater during incongruent conditions but showed no significant differences between groups. This study highlights the critical role of the SMA in managing cognitive-motor conflict during SI in PD. Reduced SMA activity and impaired APAs in FoG individuals underscore the need for targeted interventions addressing both cognitive and motor deficits to improve gait and reduce FoG episodes. These findings suggest a dissociation between motor preparation and inhibitory control in individuals with FoG.

Many cognitive and sensory processes are characterized by strong relationships between the timing of neuronal spiking and the phase of ongoing local field potential oscillations. The coupling of neuronal spiking in neocortex to the phase of alpha oscillations (8–12 Hz) has been well studied in nonhuman primates but remains largely unexplored in other mammals. How this alpha modulation of spiking differs between brain areas and cell types, as well as its role in sensory processing and decision-making, is not well understood. We used Neuropixels 1.0 probes to chronically record neural activity from somatosensory cortex, prefrontal cortex, striatum and amygdala in mice performing a whisker-based selective detection task. We observed strong spontaneous alpha modulation of single-neuron spiking activity during intertrial intervals while mice performed the task. The prevalence and strength of alpha phase modulation differed significantly across regions and between cell types. Phase modulated neurons exhibited stronger responses to both go and no-go stimuli, as well as stronger motor- and reward-related changes in firing rate, than their unmodulated counterparts. The increased responsiveness of phase modulated neurons suggests they are innervated by more diverse populations. Alpha modulation of neuronal spiking during baseline activity also correlated with task performance. In particular, many neurons exhibited strong alpha modulation before correct trials, but not before incorrect trials. These data suggest that dysregulation of spiking activity with respect to alpha oscillations may characterize lapses in attention.

The microbiota-gut-brain axis describes the bidirectional communication between the brain and the trillions of microorganisms living in the gut. Moreover, current evidence suggests that this axis can influence host behaviour and brain physiology. Previously we have shown that adult mice that have not been exposed to microbes throughout their lives display sex-specific deficits in hippocampal synaptic plasticity. However, it is not known whether this phenomenon originates during neurodevelopment or whether similar effects could be recreated with microbiome depletion in adulthood. Therefore, we explored the vulnerability of hippocampal synaptic function to altered microbiome signals, depleting the microbiome of male and female mice for 2 weeks with either an antibiotic cocktail or a single antibiotic added to drinking water. The antibiotic cocktail contained a variety of antibiotics including broad-spectrum antibiotics to ensure widescale microbiota depletion (ampicillin, vancomycin and imipenem). In addition, a more targeted depletion of Gram-positive gut bacteria was conducted using the gut-restricted antibiotic vancomycin. Ex vivo hippocampal electrophysiology measures of basal synaptic efficacy, short-term plasticity, and long-term potentiation (LTP) were then examined. We found that there was no effect of antibiotic administration on any of these measures, demonstrating the robustness of these hippocampal circuits to microbiome depletion during early adulthood. Taken together, this shows the ability of adult hippocampal plasticity to withstand a gut microbiome insult.

Psychophysical studies with human subjects investigated the dynamics of spatial visual attention around the time of saccades. They revealed that attention pointers remap against saccade direction, but at the same time show a lingering at the irrelevant retinotopic position after saccade. Involved brain areas have remained elusive. However, recordings from neurons in visual area V4 of macaques confirm remapping of spatial attention to a position opposite to the saccade direction shortly before saccade onset. Unexpectedly, in comparison with behavioral data from human subjects, a neural correlate of the lingering of spatial attention has not been observed in V4. To better understand the underlying computational mechanisms of attentional updating in V4, we developed a neurocomputational model of perisaccadic visual attention in area V4 by incorporating perisaccadic spatio-temporal signals from the frontal eye field (FEF) and the lateral intraparietal area (LIP). When we test this model on the same task, our obtained data replicate the observation of predictive remapping of spatial attention pointers in V4. Further, our model provides an intuitive explanation for the lack of lingering attention in the neural recordings: As the monkeys are only rewarded when they detect the target probe at the instructed location, they may aim at minimizing the post-saccadic spread of attention and thus weaken the attention pointer upon saccade planning. By deactivating different pathways, our model predicts that the attentional enhancement measured in V4 originates from spatial updating of a tonic attention pointer and not from a phasic saccade target attention pointer.

Despite extensive research on the effects of enriched environments in mouse models of psychiatric disorders, the role of social context remains poorly explored. Therefore, we assessed the impact of a conspecific during the evaluation of negative and cognitive symptoms in a mouse model of schizophrenia (SCZ). Male C57BL/6J mice received daily injections of ketamine (25 mg/kg) or vehicle. Behavioral testing was conducted with mice either alone or in dyads of varying familiarity. Anxiety-like behavior and habituation were assessed using the 3D maze test (3DM). Social reward was measured with a social conditioned place preference test. Finally, episodic memory was evaluated using an object recognition memory test (ORMT). Ketamine induced anxiogenic-like behavior and impaired habituation, social reward, and spatial memory. In contrast, the presence of a conspecific induced anxiolytic-like behavior, accelerated habituation, and restored social reward. Additionally, greater dyad familiarity led to better performance in the 3DM. Conversely, the presence of a conspecific did not rescue cognitive deficits in the ORMT; however, spatial navigation in the 3DM was improved. These results support that the presence of a conspecific induces social buffering and promotes prosocial behavior. Therefore, this highlights a therapeutic effect modulated by social context and introduces a new model to evaluate social cognition in a mouse model of SCZ.

Brain criticality has emerged as a rapidly growing focus of research among neuroscientists and physicists. The latest experimental evidence suggests that even isolated neurons display signs of criticality. Using a stochastic type-I parametrization of the Hodgkin–Huxley model, we investigate the origin of these critical dynamics. We show that the model adequately approximates the experimentally observed behavior, as it reproduces the qualitative relationship between the critical state and both the applied external stimulation and the spiking rate. External white noise further enhances any pre-existing critical intermittency but cannot by itself toggle the system into a critical state. The emergence of the critical state is conditional on the system's proximity to its spiking bifurcation point, and any divergence from it results in the abolition of the dynamics. We treat the neuronal membrane as a complex self-organizing system composed of interacting ion channels and propose that the observed dynamics result from an almost critical state.

The medial habenula–interpeduncular nucleus pathway is a highly conserved and densely innervated brain circuit known for its unique cholinergic transmission and exceptional expression of nicotinic acetylcholine receptors. This pathway plays a critical role in regulating motivational and emotional processes, particularly those related to nicotine consumption, avoidance behaviors, and negative emotional states. Recent advances have revealed the intricate cellular architecture and receptor diversity of this system, highlighting how specific subunits of acetylcholine receptors influence both the rewarding and aversive properties of nicotine. Genetic and functional studies in rodents and humans point to this pathway as a key regulator of nicotine intake, with potential implications for addiction treatment. In this review, we examine the organization and molecular composition of nicotinic receptors within this pathway, describe their functional and behavioral roles, and explore how cholinergic signaling contributes to nicotine dependence, stress responses, and affective states.