European Journal of Neuroscience最新文献

Circadian clock properties vary between individuals and relate to variation in entrained timing in captivity. How this variation translates into behavioural differences in natural settings, however, is poorly understood. Here, we tested in great tits whether variation in the free-running period length (tau) under constant dim light (LL) was linked to the phase angle of the entrained rhythm (“chronotype”) in captivity and in the wild, as recently indicated in our study species. We also assessed links between tau and the timing of first activity onset and offset under LL relative to the last experienced light–dark (LD) cycle. We kept 66 great tits, caught in two winters, in LL for 14 days and subsequently released them with a radio transmitter back to the wild, where their activity and body temperature rhythms were tracked for 1 to 22 days. For a subset of birds, chronotype was also recorded in the lab before release. Neither wild nor lab chronotypes were related to tau. We also found no correlation between lab and wild chronotypes. However, the first onset in LL had a positive relationship with tau, but only in males. Our results demonstrate that links between tau and phase of entrainment, postulated on theoretical grounds, may not consistently hold under natural conditions, possibly due to strong masking. This calls for more holistic research on how the many components of the circadian system interact with the environment to shape timing in the wild.

Wild birds showed chronotypes in the field that were unlinked to their circadian period length tau measured in captivity. In males only, the first onset of activity after exposure to constant dim light did correlate with tau. Our study emphasises the need to investigate clocks in the real world, including a need to better understand masking.

Combined use of fentanyl and methamphetamine (FENT + METH) has increased in recent years and has been documented in a growing number overdose deaths each year. The impact of FENT + METH on behavior and neurobiology is not well understood. In this study, male and female Long Evans rats were tested on a limited access, fixed ratio 1 self-administration schedule for increasing doses (1.25–5 μg/kg/infusion; iv) of fentanyl, with and without a single dose (0.1 mg/kg/infusion; iv) of methamphetamine, for 15 days. FENT + METH abolished dose responsiveness to fentanyl in all rats and accelerated intake in males, resulting in patterns of responding that may be more likely to result in adverse effects. Ex vivo slice voltammetry in the nucleus accumbens core showed decreases in dopamine release and reuptake (V_max) following FENT + METH exposure, compared with saline, fentanyl, and methamphetamine alone groups at baseline parameters. Further, significant decreases in dopamine release were observed across a range of stimulation intensities following FENT + METH exposure. Overall, male and female rats displayed sex-specific behavioral and neurobiological responses to FENT + METH exposure, with males displaying increased vulnerability.

In humans, adverse physical and/or psychological traumas in childhood may predispose to developing psychiatric disorders in adulthood, including panic disorder. To model early life adversity in mice, we subjected male and female C57BL/6 J mice to a limited bedding and nesting (LBN) protocol between postnatal days 2–9 and investigated its effect on responsiveness to panicogenic challenges in adulthood. Panic-like escape behaviour was assessed during exposure to a high concentration of CO₂ (20%) or in the beetle mania task (BMT), used to model respiratory and non-respiratory-related types of panic respectively. Neonatal exposure to LBN increased panic-like jumping during the CO₂ challenge in male but not female mice. In an initial pharmacological validation of the BMT as a panic-inducing paradigm, undirected jumping and horizontal escape behaviours were reduced significantly by the panicolytic alprazolam (0.05 and 0.1mg.kg⁻¹ i.p.) whilst tolerance to the close proximity of the aversive robo-beetle increased. The anxiolytic diazepam (1 mg.kg⁻¹ i.p.) reduced only the number of horizontal escape attempts. In both sexes, previous experience of LBN significantly enhanced the number of horizontal escape episodes, indicating a pro-panic phenotype. Directed escape to access a safe ledge on the wall of the test arena, which was seen only in males, was also reduced significantly following LBN. These findings indicate that early life adversity produced by fragmented and unpredictable maternal care promotes a sex-specific increase in susceptibility to panic-like behaviour in adulthood. Whilst non-respiratory-related panic-like behaviour was enhanced in both sexes, females were resilient to respiratory-related challenges.

From adolescence, women become more likely to experience fear dysregulation. Oral contraceptives (OCs) can modulate the brain regions involved in fear processes. OCs are generally used for years and often initiated during adolescence, a sensitive period where certain brain regions involved in the fear circuitry are still undergoing important reorganization. It remains unknown whether OC use during adolescence may induce long-lasting changes in the fear circuitry. This study aimed to examine whether age of onset moderated the relationship between duration of use and fear-related brain structures. We collected structural MRI data in 98 healthy adult women (61 current users, 37 past users) and extracted grey matter volumes (GMV) and cortical thickness (CT) of key regions of the fear circuitry. Non-linear multiple regressions revealed interaction effects between age of onset and quadratic duration of use on GMV of the right hippocampus and right ventromedial prefrontal cortex (vmPFC). Among women who initiated OCs earlier in adolescence, a short duration of use was associated with smaller hippocampal GMV and thicker vmPFC compared to a longer duration of use. For both GMV and CT of the right vmPFC, women with an early OC onset had more grey matter at a short duration of use than those with a later onset. Our results suggest that OC use earlier in adolescence may induce lasting effects on structural correlates of fear learning and its regulation. These findings support further investigation into the timing of OC use to better comprehend how OCs could disrupt normal brain development processes.

The paraventricular nucleus of the hypothalamus (PVN) regulates physiological and behavioural responses evoked by stressful stimuli, but the local neurochemical and signalling mechanisms involved are not completely understood. The soluble guanylate cyclase (sGC) within the PVN is implicated in autonomic and cardiovascular control in rodents under resting conditions. However, the involvement of PVN sGC-mediated signalling in stress responses is unknown. Therefore, we investigated the role of sGC within the PVN in cardiovascular, autonomic, neuroendocrine, and local neuronal responses to acute restraint stress in rats. Bilateral microinjection of the selective sGC inhibitor ODQ (1 nmol/100 nl) into the PVN reduced both the increased arterial pressure and the drop in cutaneous tail temperature evoked by restraint stress, while the tachycardia was enhanced. Intra-PVN injection of ODQ did not alter the number of Fos-immunoreactive neurons in either the dorsal cap parvocellular (PaDC), ventromedial (PaV), medial parvocellular (PaMP), or lateral magnocelllular (PaLM) portions of the PVN following acute restraint stress. Local microinjection of ODQ into the PVN did not affect the restraint-induced increases in plasma corticosterone concentration. Taken together, these findings suggest that sGC-mediated signalling in the PVN plays a key role in acute stress-induced pressor responses and sympathetically mediated cutaneous vasoconstriction, whereas the tachycardiac response is inhibited. Absence of an effect of ODQ on corticosterone and PVN neuronal activation in and the PaV and PaMP suggests that PVN sGC is not involved in restraint-evoked hypothalamus-pituitary-adrenal (HPA) axis activation and further indicates that autonomic and neuroendocrine responses are dissociable at the level of the PVN.

Age-related hearing impairment (ARHI) is commonly associated with decreased auditory temporal resolution caused by auditory neurodegeneration. Age-related deterioration in gap detection ability, resulting in poor temporal auditory processing, is often attributed to pathophysiological changes in both the peripheral and central auditory systems. This study aimed to investigate whether the gap detection ability declines in the early stages of ageing and to determine its usefulness in detecting peripheral and central auditory degeneration. The study used 1-month-old (1 M), 6-month-old (6 M) and 12-month-old (12 M) mice to examine changes in gap detection ability and associated auditory pathophysiology. Although hearing thresholds did not significantly differ between the groups, the amplitude of auditory brainstem response (ABR) wave I decreased significantly in an age-dependent manner, consistent with age-related cochlear synaptopathy. The relative ABR amplitude ratio of waves 2 and 5 to wave 1 was significantly increased in 12 M mice, indicating that the central auditory system had increased in relative neuroactivity. A significant increase in gap detection thresholds was observed in 12 M mice compared to 1 M mice. Although cochlear synaptopathy and central hyperactivity were positively correlated with gap detection thresholds, central hyperactivity strongly influenced gap detection ability. In the cochlear nucleus and auditory cortex, the inhibitory synaptic expression of GAD65 and the expression of parvalbumin were significantly decreased in 12 M mice, consistent with central hyperactivity. Evaluating gap detection performance may allow the identification of decreased auditory temporal resolution in the early stages of ARHI, which is strongly associated with auditory neurodegeneration.

Acetylcholine esterases (AChEs) are essential enzymes in cholinergic synapses, terminating neurotransmission by hydrolysing acetylcholine. While membrane bound AChEs at synaptic clefts efficiently perform this task, soluble AChEs are less stable and effective, but function over broader areas. In vertebrates, a single gene produces alternatively spliced forms of AChE, whereas invertebrates often have multiple genes, producing both enzyme types. Despite their significance as pesticide targets, the physiological roles of invertebrate AChEs remain unclear. Here, we characterized seven putative AChEs in the wandering spider, Cupiennius salei, a model species for neurophysiological studies. Sequence analyses and homology modeling predicted CsAChE7 as the sole stable, membrane-bound enzyme functioning at synaptic clefts, while the others are likely soluble enzymes. In situ hybridization of sections from the spider's nervous system revealed CsAChE7 transcripts co-localizing with choline acetyltransferase in cells that also exhibited AChE activity. CsAChE7 transcripts were also found in rapidly adapting mechanosensory neurons, suggesting a role in precise and transient activation of postsynaptic cells, contrasting with slowly adapting, also cholinergic, neurons expressing only soluble AChEs, which allow prolonged activation of postsynaptic cells. These findings suggest that cholinergic transmission is influenced not only by postsynaptic receptors but also by the enzymatic properties regulating acetylcholine clearance. We also show that acetylcholine is a crucial neurotransmitter in the spider's visual system and sensory and motor pathways, but absent in excitatory motor neurons at neuromuscular junctions, consistent with other arthropods. Our findings on sequence structures may have implications for the development of neurological drugs and pesticides.

Previous studies have suggested that the morphology and function of the thalamus and cortex are abnormal in patients with knee osteoarthritis (KOA). However, whether the thalamocortical network is differentially affected in this disorder is unknown. In this study, we examined functional and effective connectivity between the thalamus and major divisions of the cortex in 27 healthy controls and 27 KOA patients using functional magnetic resonance imaging. We also explored the topological features of the brain via graph theory analysis. The results suggested that patients with KOA had significantly reduced resting-state functional connectivity (rsFC) of the thalamo–sensorimotor pathway; enhanced rsFC of the thalamo–medial/lateral frontal cortex (mFC/LFC), parietal, temporal and occipital pathways; reduced effective connectivity of the left sensorimotor-to-thalamus pathway; and enhanced effective connectivity of the right thalamus-to-sensorimotor pathway compared with healthy controls. The functional connectivity of the thalamo–sensorimotor and thalamo–mFC pathways was enhanced when patients performed the multisource interference task. Moreover, patients with KOA presented altered nodal properties associated with thalamocortical circuits, including the thalamus, amygdala, and regions in default mode networks, compared with healthy controls. The correlation analysis suggested a significant negative correlation between thalamo–mFC rsFC and pain intensity, between thalamo–sensorimotor task-related connectivity and disease duration/depression scores, and a positive correlation between right frontal nodal properties and pain intensity in KOA patients. Taken together, these findings establish abnormal and differential alterations in the thalamocortical network associated with pain characteristics in KOA patients, which extends our understanding of their role in the pathophysiology of KOA.

Working memory (WM) involves the capacity to maintain and manipulate information over short periods. Previous research has suggested that fronto-parietal activities play a crucial role in WM. However, there remains no agreement on the effect of working memory load (WML) on neural activities and haemodynamic responses. Here, our study seeks to examine the effect of WML through simultaneous electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS). In this study, a delay change detection task was conducted on 23 healthy volunteers. The task included three levels: one item, three items and five items. The EEG and fNIRS were simultaneously recorded during the task. Neural activities and haemodynamic responses at prefrontal and parietal regions were analysed using time-frequency analysis and weighted phase-lag index (wPLI). We observed a significant enhancement in prefrontal and parietal β suppression as WML increased. Furthermore, as WML increased, there was a notable enhancement in fronto-parietal connectivity (FPC), as evidenced by both EEG and fNIRS. Correlation analysis indicated that as WML increased, there was a potential for enhancement of neurovascular coupling (NVC) of FPC.

Virtual reality (VR)–guided motor imagery (MI) is a widely used approach for motor rehabilitation, especially for patients with severe motor impairments. Most approaches provide visual guidance from the first-person perspective (1PP). MI training with visual guidance from the third-person perspective (3PP) remains largely unexplored. We argue that 3PP MI training has its own advantages and can supplement 1PP MI. For some movements beyond the view of 1PP, such as shoulder shrugging and other axial movements, MI are suitable performed under 3PP. However, the efficiency of existing paradigms for 3PP MI is unsatisfactory. We speculate that the absence of sense of body ownership (SOO) from 3PP could be one possible factor and hypothesize that 3PP MI could be enhanced by eliciting SOO over a 3PP avatar. Based on our hypothesis, a novel paradigm was proposed to enhance 3PP MI by inducing full-body illusion (FBI) from 3PP, which is similar to the so-called out-of-body experience (OBE), using synchronous visuo-tactile stimulus with VR. The event-related Electroencephalograph (EEG) desynchronization (ERD) at motor-related regions from 31 healthy participants were calculated and compared with a control paradigm without “OBE” FBI induction. This study attempts to enhance 3PP MI with FBI induction. It offers an opportunity to perform MI guided by action observation from 3PP with elicited SOO to the observed avatar. We believe that 3PP MI could provide more possibilities for effective rehabilitation training, when SOO could be elicited to a virtual avatar and the present work demonstrates its viability and effectiveness.