Brain and neuroscience advances最新文献

Although a role of the thalamus in different arousal and awareness states is well established, there is a surprising lack of knowledge on subregional specificity within this complex, multinucleated structure of the diencephalon. In their recent paper 'Extrasynaptic GABA-A receptors in central medial thalamus mediate anaesthesia in rats', Muheyati et al. evaluated whether GABA_A receptors expressed in the central medial (CM), paraventricular (PV) or lateral mediodorsal (MD) nuclei of the thalamus contribute to the loss of the righting reflex (LORR) in rats. Deficits in this reflex have previously been interpreted as a surrogate marker of altered levels of consciousness. Using a range of convergent techniques, the authors report the novel finding that delta subunit-expressing GABA_A receptors in the CM contribute to distinct awareness states. This important discovery implicates a tonic GABA_A-mediated conductance in the CM that may be relevant for minimally conscious states and other conditions of altered awareness.

Using genetically modified animals to model neurodevelopmental conditions helps better our understanding of biology underlying these conditions. Animal research has unique characteristics not shared with clinical research, meaning systematic review methods must be adapted to this context. We aim to evaluate the quantity, characteristics, and reporting quality of systematic reviews which synthesise research using genetically modified animals to model neurodevelopmental conditions. On 23 January 2023, we searched PubMed, Embase, and the Web of Science Core Collection to identify systematic reviews of genetic neurodevelopmental condition animal research where the modified gene was one in a list of 102 genes associated with neurodevelopmental conditions identified through large-scale exome sequencing or Fmr1, Mecp2, or Ube3a. Two independent reviewers screened studies based on full text and assessed the reporting quality of relevant reviews using an adapted version of the PRISMA checklist (PRISMA-Pre). Twelve review publications met our criteria. We found mixed levels of reporting: items such as identifying the publication as a systematic review in the title, search strategies, and funding sources being well reported, and others such as protocol registration and data sharing less well reported. We also identified 19 review registrations via PROSPERO, most of which remain unpublished after their anticipated end dates. Systematic reviews are limited by lack of reporting. Increased awareness of reporting guidelines may help authors increase the transparency and reproducibility, and therefore the reliability, of their systematic reviews.

On November 20-21 2023, the Royal Society in London hosted a landmark scientific meeting led by Professor Wickliffe C Abraham, Professor Timothy VP Bliss, Professor Graham L Collingridge, and Professor Richard GM Morris. The conference, commemorating the 50th anniversary of the discovery of Long-Term Potentiation, focused on discussing the latest research and developments in the field of synaptic plasticity. We have invited former presidents of the British Neuroscience Association, Professor Graham Collingridge CBE FRS and Professor Richard Morris CBE FRS, for interviews.

Although neuritic plaques - comprised of aggregated fibrils of the misfolded protein, amyloid β (Aβ) - have formed a central focus of Alzheimer's disease (AD) research for decades, it is now well understood that plaque burden alone is a poor correlate of cognitive decline. This is highlighted especially when compared against other neuropathological hallmarks, such as synapse loss (the strongest correlate) and hyperphosphorylated protein tau. However, it is known that Familial AD arises due to autosomal dominant mutations directly influencing the generation of Aβ, suggesting that Aβ pathology may play a key upstream role in the disease. Such contrasting lines of evidence have thus raised questions as to why some aged individuals with high plaque burden develop AD while others remain cognitively healthy. In their recent study, published in Analytical Chemistry (June 2024), Enzlein and colleagues aimed to investigate whether differences in the molecular composition of plaques between individuals with sporadic Alzheimer's disease (N = 9) versus age-matched amyloid positive but cognitively unaffected controls (N = 8) could go towards explaining this outstanding question in the field. Using novel methods integrating mass spectrometry imaging with machine learning feature extraction, the authors compared peptide and lipid profiles to a resolving limit of 400 μm2 for >5000 individual plaques. In doing so, a distinct peptide signature was identified in sporadic Alzheimer's disease plaques that was characterised by strongly increased aggregation of the short amyloid β isoform, Aβ1-38 coupled with a lesser co-aggregation of pyroglutamate-modified Aβ3-42pE. Sporadic Alzheimer's disease plaques also demonstrated a robust lipid signature denoted by an increased presence of cell membrane components, GM1 and GM2 gangliosides. Here, we review this work; aiming to place these findings within the context of existing literature and with a view to discussing their importance in developing our current knowledge of Alzheimer's disease.

Disgust is a vital emotion in the avoidance of illness. Human adults across cultures show disgust towards sources of potential contamination or pathogens, and elect to avoid their ingestion or even to look at them. Stomach rhythms appear to play an important role: disgust reduces normogastric power, and the pharmacological normalisation of gastric state reduces disgust avoidance. Human children are remarkably slow to develop disgust as measured by self-report and facial expressions. Here, we investigate whether disgust-induced avoidance (measured using eye tracking) and changes in gastric rhythm (measured using electrogastrography) exist in children aged 5 to 13 years (N = 45). We found that children in this bracket showed oculomotor avoidance of disgusting stimuli in a preferential-looking task, similar to adult samples in previous research. However, in contrast to adult samples in previous research, children did not show an attenuation in normogastric power. These findings could suggest that avoidance behaviour precedes gastric involvement during disgust. This would support the idea that children initially respond to parental modelling: parents set (and enforce) the social norm of disgust avoidance, and children initially conform and only later do they internalise disgust as an interoceptive signal. Alternatively, the employed stimuli could have been potent enough to induce oculomotor avoidance, but not a gastric response. Research is slim in this area, and future work should focus on elucidating the role of the stomach in disgust, and on longitudinal studies of disgust development from childhood to adolescence.

In this article, we critique the hypothesis that different varieties of impulsivity, including impulsiveness present in attention-deficit hyperactivity disorder, encompass an accelerated perception of time. This conceptualisation provides insights into how individuals with attention-deficit hyperactivity disorder have the capacity to maximise cognitive capabilities by more closely aligning themselves with appropriate environmental contexts (e.g. fast paced tasks that prevent boredom). We discuss the evidence for altered time perception in attention-deficit hyperactivity disorder alongside putative underlying neurobiological substrates, including a distributed brain network mediating time perception over multiple timescales. In particular, we explore the importance of temporal representations across the brain for time perception and symptom manifestation in attention-deficit hyperactivity disorder, including a prominent role of the hippocampus and other temporal lobe regions. We also reflect on how abnormalities in the perception of time may be relevant for understanding the aetiology of attention-deficit hyperactivity disorder and mechanism of action of existing medications.

The binding of information from different sensory or neural sources is critical for associative memory. Previous research in animals suggested that the timing of theta oscillations in the hippocampus is critical for long-term potentiation, which underlies associative and episodic memory. Studies with human participants showed correlations between theta oscillations in medial temporal lobe and episodic memory. Clouter et al. directly investigated this link by modulating the intensity of the luminance and the sound of the video clips so that they 'flickered' at certain frequencies and with varying synchronicity between the visual and auditory streams. Across several experiments, better memory was found for stimuli that flickered synchronously at theta frequency compared with no-flicker, asynchronous theta, or synchronous alpha and delta frequencies. This effect - which they called the theta-induced memory effect - is consistent with the importance of theta synchronicity for long-term potentiation. In addition, electroencephalography data showed entrainment of cortical regions to the visual and auditory flicker, and that synchronicity was achieved in neuronal oscillations (with a fixed delay between visual and auditory streams). The theoretical importance, large effect size, and potential application to enhance real-world memory mean that a replication of theta-induced memory effect would be highly valuable. The present study aimed to replicate the key differences among synchronous theta, asynchronous theta, synchronous delta, and no-flicker conditions, but within a single experiment. The results do not show evidence of improved memory for theta synchronicity in any of the comparisons. We suggest a reinterpretation of theta-induced memory effect to accommodate this non-replication.

In their recently published study, Gil, Valente and Shemesh combined behaviour, functional magnetic resonance imaging, electroencephalography and causal interventions to establish and validate a cortical processing substrate underlying the transition from static to dynamic visual states in the rat. Their research highlights the superior colliculus as the primary mediator of visual temporal discrimination by showing a direct correlation between behavioural and cortically derived flicker fusion frequency thresholds. This work provides the first empirical evidence addressing the previously established disparity between behavioural and cortically derived flicker fusion frequency thresholds. It demonstrates how important convergent multimodal approaches are to mapping and validating previously disputed cortical pathways. Here, we discuss and evaluate their work, suggesting possible future applications in the field of behavioural neuroscience.

Ischaemic stroke presents a significant problem worldwide with no neuroprotective drugs available. Many of the failures in the search for neuroprotectants are attributed to failure to translate from pre-clinical models to humans, which has been combatted with rigorous pre-clinical stroke research guidelines. Here, we present post hoc analysis of a pre-clinical stroke trial, conducted using intraluminal filament transient middle cerebral artery occlusion in the stroke-prone spontaneously hypertensive rat, whereby unscheduled changes were implemented in the animal housing facility. These changes severely impacted body weight post-stroke resulting in a change from the typical body weight of 90.6% of pre-surgery weight post-stroke, to on average 80.5% of pre-surgery weight post-stroke. The changes also appeared to impact post-stroke blood pressure, with an increase from 215.4 to 240.3 mmHg between housing groups, and functional outcome post-stroke, with a 38% increased latency to contact in the sticky label test. These data highlight the importance of tightly controlled housing conditions when using physiological or behavioural measurements as a primary outcome.

The modulation of synaptic efficacy by group I metabotropic glutamate receptors is dysregulated in several neurodevelopmental and neurodegenerative disorders impacting cognitive function. The progression and severity of these and other disorders are affected by biological sex, and differences in metabotropic glutamate receptor signalling have been implicated in this effect. In this study, we have examined whether there are any sex-dependent differences in a form of long-term depression of synaptic responses that is triggered by application of the group I metabotropic glutamate receptor agonist 3,5-dihydroxyphenylglycine (DHPG). We studied DHPG-induced long-term depression at the Schaffer collateral-commissural pathway in area CA1 of hippocampal slices prepared from three separate age groups of Sprague Dawley rats. In both juvenile (2-week-old) and young adult (3-month-old) rats, there were no differences between sexes in the magnitude of long-term depression. However, in older adult (>1-year-old) rats, DHPG-induced long-term depression was greater in males. In contrast, there were no differences between sexes with respect to basal synaptic transmission or paired-pulse facilitation in any age group. The specific enhancement of metabotropic glutamate receptor-dependent long-term depression in older adult males, but not females, reinforces the importance of considering sex as a factor in the study and treatment of brain disorders.