European Journal of Neuroscience最新文献

{"title":"Synaptic Targets and Cellular Sources of CB1 Cannabinoid Receptor and Vesicular Glutamate Transporter-3 Expressing Nerve Terminals in Relation to GABAergic Neurons in the Human Cerebral Cortex","authors":"Peter Somogyi,&nbsp;Sawa Horie,&nbsp;Istvan Lukacs,&nbsp;Emily Hunter,&nbsp;Barbara Sarkany,&nbsp;Tim James Viney,&nbsp;James Livermore,&nbsp;Puneet Plaha,&nbsp;Richard Stacey,&nbsp;Olaf Ansorge,&nbsp;Salah El Mestikawy,&nbsp;Qianru Zhao","doi":"10.1111/ejn.16652","DOIUrl":"10.1111/ejn.16652","url":null,"abstract":"<p>Cannabinoid receptor 1 (CB1) regulates synaptic transmission through presynaptic receptors in nerve terminals, and its physiological roles are of clinical relevance. The cellular sources and synaptic targets of CB1-expressing terminals in the human cerebral cortex are undefined. We demonstrate a variable laminar pattern of CB1-immunoreactive axons and electron microscopically show that CB1-positive GABAergic terminals make type-2 synapses innervating dendritic shafts (69%), dendritic spines (20%) and somata (11%) in neocortical layers 2–3. Of the CB1-immunopositive GABAergic terminals, 25% were vesicular-glutamate-transporter-3 (VGLUT3)-immunoreactive, suggesting GABAergic/glutamatergic co-transmission on dendritic shafts. In vitro recorded and labelled VGLUT3 or CB1-positive GABAergic interneurons expressed cholecystokinin, vasoactive-intestinal-polypeptide and calretinin, had diverse firing, axons and dendrites, and included rosehip, neurogliaform and basket cells, but not double bouquet or axo-axonic cells. CB1-positive interneurons innervated pyramidal cells and GABAergic interneurons. Glutamatergic synaptic terminals formed type-1 synapses and some were positive for CB1 receptor with a distribution that appeared different from that in GABAergic terminals. From the sampled VGLUT3-positive terminals, 60% formed type-1 synapses with dendritic spines (80%) or shafts (20%) and 52% were also positive for VGLUT1, suggesting intracortical origin. Some VGLUT3-positive terminals were immunopositive for vesicular-monoamine-transporter-2, suggesting 5-HT/glutamate co-transmission. Overall, the results show that CB1 regulates GABA release mainly to dendritic shafts of both pyramidal cells and interneurons and predict CB1-regulated co-release of GABA and glutamate from single cortical interneurons. We also demonstrate the co-existence of multiple vesicular glutamate transporters in a select population of terminals probably originating from cortical neurons and innervating dendritic spines in the human cerebral cortex.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"61 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcranial Magnetic Stimulation Inter-Pulse Interval Does Not Influence Corticospinal Excitability to the Biceps Brachii During Submaximal Isometric Elbow Flexion","authors":"David H. Imeson,&nbsp;Lea Gerditschke,&nbsp;Liana E. Brown,&nbsp;Davis A. Forman","doi":"10.1111/ejn.16671","DOIUrl":"10.1111/ejn.16671","url":null,"abstract":"<p>Previous research on resting muscles has shown that inter-pulse interval (IPI) duration influences transcranial magnetic stimulation (TMS) responses, which can introduce serious confounding variables into investigations if not accounted for. However, it is far less clear how IPI influences TMS responses in active muscles. Thus, the purpose of this study was to examine the relationship between IPI and corticospinal excitability during submaximal isometric elbow flexion. Corticospinal excitability to the biceps and triceps brachii was measured using motor evoked potentials (MEPs) elicited via TMS. Stimulation intensity was set to 120% of the biceps brachii's active motor threshold while participants produced 10% of their biceps' maximal muscle activity. TMS was delivered as separate trains of five stimulations, with experimental conditions differing between IPIs of 4, 6, 8, 10, 12 or 14 s. Results demonstrated that IPI had no influence on MEP amplitudes for either the biceps or triceps. However, when MEP amplitudes were expressed as a unitless ratio to pre-stimulus muscle activity, a main effect of time was found for the biceps; MEP amplitudes progressively decreased with successive stimulations (MEP 1:32.8 ± 5.9; MEP 5:27.7 ± 4.3, <i>p</i> &lt; 0.05). These results suggest that IPI is unlikely to represent a confounding variable in TMS studies utilizing active contractions. However, studies looking to compare the amplitudes of single MEPs over time should be aware of the possibility that amplitudes may decrease with continuous stimulation. Future research should seek to examine even longer IPIs and explore the influence of higher stimulation intensities.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"61 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apples and oranges: Conceptual review as task analysis method1","authors":"Annemarie van Stee","doi":"10.1111/ejn.16623","DOIUrl":"10.1111/ejn.16623","url":null,"abstract":"<p>Conceptual review is a method to address issues of task comparability and task validity in cognitive neuroscience. Meta-analyses within cognitive neuroscience (CNS) as well as integration of neuroscientific findings with findings from adjacent disciplines both involve gathering studies that have purportedly investigated the same mental concept. After all, it is no use comparing apples and oranges. Tasks, and in particular the experimental contrasts implemented through tasks, determine whether studies are in fact comparable. Yet studies tend to be grouped together or kept apart based on the mental label researchers have applied and unfortunately, labels are an unreliable proxy for experimental contrasts. Different contrasts may receive the same label: ‘working memory’ studies rely on a variety of contrasts, derived from a variety of tasks. Vice versa, the same contrast may receive different labels: ‘task switching’ and ‘working memory’ studies can be exactly the same in terms of their experimental contrast. Label use thus obscures comparability problems. What is more, even when experimental contrasts are comparable, they may be invalid operationalizations of the mental label attached to them. In this paper, I introduce conceptual review as a method for task analysis. It can stand on its own or be combined with a cognitive ontology. Conceptual review applies philosophical strategies for analysing concepts to methodological choices in CNS studies, to uncover their conceptual implications. Conceptual review thus sheds light on the precise concept that was studied and thereby, on the comparability of CNS studies and the validity of tasks.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"61 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of odorants in odour mixtures among healthy people and patients with olfactory dysfunction","authors":"Eva Drnovsek,&nbsp;Kristina Weitkamp,&nbsp;Venkatesh N. Murthy,&nbsp;Edanur Gurbuz,&nbsp;Antje Haehner,&nbsp;Thomas Hummel","doi":"10.1111/ejn.16633","DOIUrl":"10.1111/ejn.16633","url":null,"abstract":"<p>Target odorant detection in mixtures has been shown to become more difficult as the number of background odorants increases and falls below chance level in mixtures with 16 components. Our aim was to investigate target odorant detection in mixtures among healthy people and compare it between dysosmic patients and age- and gender-matched controls. Participants underwent extensive olfactory testing and performed two target odorant detection tasks. Eugenol (‘clove’) and phenylethanol (PEA, ‘rose’) were target odorants for all participants, whereas a third target was randomised. For each target odorant in task one (task two), there were four steps. Mixtures contained two (three) odorants in the first step and up to seven (eight) odorants in the fourth step. In each step, participants were asked to choose the sample with the target odorant from the three (two) jars presented. The study included 90 healthy people and 40 patients. As expected, probability of successful target odorant detection decreased as the number of odorants in the mixture increased. However, even when there were seven (eight) odorants in the mixture, around 50% (50%) of healthy people detected Eugenol and around 30% (40%) detected PEA. Furthermore, both distributions of successful target odorant detection differed from the expected binominal distribution of chance (<i>p</i> &lt; 0.001). Patients performed worse at detecting Eugenol or PEA at each step than controls. Furthermore, there were significant positive correlations between task scores and olfactory function. In conclusion, target odorant detection is influenced by the target odorant, number of background odorants, and individual olfactory function.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"61 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Laser-Induced Olfactory Bulbectomy in Adult Zebrafish as a Novel Putative Model for Affective Syndrome: A Research Tribute to Brian Leonard","authors":"Evgeny V. Nekhoroshev,&nbsp;Maxim A. Kleshchev,&nbsp;Andrey D. Volgin,&nbsp;Anton D. Shavlyakov,&nbsp;Xixin Bao,&nbsp;Shenghao Wang,&nbsp;Murilo S. de Abreu,&nbsp;Tamara G. Amstislavskaya,&nbsp;Allan V. Kalueff","doi":"10.1111/ejn.16660","DOIUrl":"10.1111/ejn.16660","url":null,"abstract":"<div>\u0000 \u0000 <p>Inducing multiple neurobehavioural and neurochemical deficits, olfactory bulbectomy (OBX) has been developed as a rodent model of depression with potential for antidepressant drug screening. However, the generality of this model in other vertebrate taxa remains poorly understood. A small freshwater teleost fish, the zebrafish (<i>Danio rerio</i>), is rapidly becoming a common model species in neuroscience research. Capitalizing on a recently developed model of noninvasive targeted laser ablation of zebrafish brain, here we report an OBX model in adult fish. An easy-to-perform noninvasive method of inducing affective syndrome-like behavioural deficits in fish, it extends the generality of OBX to other taxa beyond mammals, also offering several practical advantages and novel lines of research in experimental modelling of CNS disorders. The work is a scientific tribute to the legacy of Brian Leonard (1936–2023), a great friend and a brilliant scientist who introduced OBX as a rodent model for affective pathobiology and whose advice and encouragement have inspired the present study.</p>\u0000 </div>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"61 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating frontoparietal networks and activation in children with mathematics learning difficulties: Cases with different deficit profiles","authors":"Fengjuan Wang,&nbsp;Azilawati Jamaludin","doi":"10.1111/ejn.16629","DOIUrl":"10.1111/ejn.16629","url":null,"abstract":"<p>Approximately 15%–20% of school-aged children suffer from mathematics learning difficulties (MLD). Most children with developmental dyscalculia (DD) or MLD also have comorbid cognitive deficits. Recent literature suggests that research should focus on uncovering the neural underpinnings of MLD across more inclusive samples, rather than limiting studies to pure cases of DD or MLD with highly stringent inclusion criteria. Therefore, this study aims to identify neural aberrancies that may be common across multiple MLD cases with different deficit profiles. Nine MLD cases and 45 typically developing (TD) children, all around 7 years old (27 boys), were recruited. Using functional near-infrared spectroscopy (fNIRS), brain data were collected during an approximate resting state and a mathematical computation task (addition). Graph theory was then applied to assess global and nodal network indicators of brain function. When comparing the network indicators and brain activation of the MLD cases to those of TD children, no unified neural aberrancy was found across all cases. However, three MLD cases did show distinct neural aberrancies compared to TD children. The study discusses the implications of these findings, considering both the neural aberrancies in the three MLD cases and the neural similarities found in the other six cases, which were comparable to those of the TD children. This raises important questions about the presence and nature of aberrant neural indicators in MLD across large cohorts and highlights the need for further research in this area.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"61 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topological features of brain functional networks are reorganized during chronic tinnitus: A graph-theoretical study","authors":"Shuting Han,&nbsp;Yongcong Shen,&nbsp;Xiaojuan Wu,&nbsp;Hui Dai,&nbsp;Yonggang Li,&nbsp;Jisheng Liu,&nbsp;Duo-duo Tao","doi":"10.1111/ejn.16643","DOIUrl":"10.1111/ejn.16643","url":null,"abstract":"<p>This study aimed to investigate the topological properties of brain functional networks in patients with tinnitus of varying durations. A total of 51 tinnitus patients (divided into recent-onset tinnitus (ROT) and persistent tinnitus (PT) groups) and 27 healthy controls (HC) were recruited. All participants underwent resting-state functional MRI and audiological assessments. Graph theory was used to examine brain network topology.</p><p>The results showed that the ROT group exhibited lower clustering coefficient, gamma, sigma and local efficiency compared to both the HC and PT groups (all <i>P</i> &lt; 0.05). Significant reductions in nodal clustering coefficient and local efficiency were found in the left caudate nucleus and left olfactory cortex, while increased nodal centralities were observed in the left orbital middle frontal gyrus and left postcentral gyrus in ROT patients (all <i>P</i> &lt; 0.05). Furthermore, the ROT group had decreased nodal clustering in the right lenticular putamen and reduced nodal efficiency in the left olfactory cortex compared to both PT patients and HCs (all <i>P</i> &lt; 0.05).</p><p>Additionally, PT patients showed weaker functional connectivity between the subcortical and occipital lobe modules, as well as between the prefrontal and intra-frontal modules, compared to ROT patients. However, intra-module connectivity in the subcortical module was stronger in PT patients than in HCs.</p><p>These findings suggest that recent-onset tinnitus is associated with alterations in brain network topology, but many of these changes are restored with the persistence of tinnitus.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"61 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fast Neuronal Calcium Signals in Brain Slices Loaded With Fluo-4 AM Ester","authors":"Ömer Yusuf İpek,&nbsp;Fatima Abbas,&nbsp;Hajar Sajidy,&nbsp;Marco Canepari","doi":"10.1111/ejn.16657","DOIUrl":"10.1111/ejn.16657","url":null,"abstract":"<p>Staining brain slices with acetoxymethyl ester (AM) Ca²⁺ dyes is a straightforward procedure to load multiple cells, and Fluo-4 is a commonly used high-affinity indicator due to its very large dynamic range. It has been shown that this dye preferentially stains glial cells, providing slow and large Ca²⁺ transients, but it is questionable whether and at which temporal resolution it can also report Ca²⁺ transients from neuronal cells. Here, by electrically stimulating mouse hippocampal slices, we resolved fast neuronal signals corresponding to 1%–3% maximal fluorescence changes. Specifically, by recording Ca²⁺ fluorescence at 2000 frames/s from multiple sites both in the CA3 and in the CA1 regions, we observed that the signal measured near the stimulating electrode, positioned on the mossy fibre pathway, was not blocked by perfusion with 10 μM NBQX and 50 μM AP5, preventing excitatory synaptic transmission. In contrast, this signal was fully blocked by additional perfusion with 1 μM tetrodotoxin, inhibiting voltage-gated Na⁺ channels and neuronal action potentials. We also present recordings obtained in the presence of 10 μM of the GABA_A receptor antagonist bicuculline, or of 50 μM of the voltage-gated K⁺ channel inhibitor 4-aminopyridine, exhibiting a wide propagation of the signal from CA3 to CA1 regions under conditions that mimic epileptic seizures. Altogether, while Fluo-4 AM remains a preferable indicator for reporting Ca²⁺ signals from astrocytes at slow temporal resolution, we demonstrated that it can be also utilised for analysing fast neuronal network activity elicited by electrical stimulation in brain slices.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"61 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gender Differences in the Association Between Anxiety and Interoceptive Insight","authors":"Olivia K. Harrison,&nbsp;Laura Köchli,&nbsp;Stephanie Marino,&nbsp;Lucy Marlow,&nbsp;Sarah L. Finnegan,&nbsp;Ben Ainsworth,&nbsp;Benjamin J. Talks,&nbsp;Bruce R. Russell,&nbsp;Samuel J. Harrison,&nbsp;Kyle T. S. Pattinson,&nbsp;Stephen M. Fleming,&nbsp;Klaas E. Stephan","doi":"10.1111/ejn.16672","DOIUrl":"10.1111/ejn.16672","url":null,"abstract":"<p>Anxiety is one of the most common and debilitating mental health disorders, and is related to changes in interoception (perception of bodily states). While anxiety is more prevalent in women than men, gender differences in interoception-anxiety associations are often overlooked. Here, we examined gender-specific relationships between anxiety and interoception in the breathing domain, utilising multicentre data pooled from four study sites (<i>N</i> = 175; 51% women). State anxiety scores were quantified via the Spielberger State–Trait Anxiety Inventory, and breathing-related interoceptive dimensions via an inspiratory load task to quantify sensitivity, decision bias, metacognitive bias (confidence in interoceptive decisions), and metacognitive insight (congruency between performance and confidence). Regression analyses revealed a significant negative relationship between state anxiety and metacognitive bias (β = −0.28; <i>p</i> = 0.01) and insight (β = −0.09; 95% highest density interval [HDI] in a hierarchical Bayesian regression = [−0.18, −0.004]) across the whole sample, while state anxiety did not relate to interoceptive sensitivity nor decision bias. While no mean interoceptive effects relating to gender were observed, the relationship between anxiety and metacognitive insight towards breathing was driven by women (women: β = −0.18; HDI = [−0.31, −0.05]; men: β = 0.02; HDI = [−0.12, 0.15]) with a significant interaction effect (β difference = −0.20; HDI = [−0.37, −0.01]), which did not hold for trait anxiety nor depression measures. In summary, state anxiety was associated with decreased metacognitive bias across all participants, while decreased interoceptive insight was only associated with anxiety in women but not men. Therefore, treatment programmes focusing on interoceptive metacognitive bias may be useful for all anxiety patients, while interoceptive insight might represent a specific treatment target for women with anxiety.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"61 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11728262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond the Illusion of Controlled Environments: How to Embrace Ecological Pertinence in Research?","authors":"Cassandre Vielle","doi":"10.1111/ejn.16661","DOIUrl":"10.1111/ejn.16661","url":null,"abstract":"<p>Through the lens of preclinical research on substance use disorders (SUD), I propose a reflection aimed at re-evaluating animal models in neuroscience, with a focus on ecological relevance. While rodent models have provided valuable insights into the neurobiology of SUD, the field currently faces a validation crisis, with findings often failing to translate into effective human treatments. Originally designed to address the lack of reproducibility in animal studies, the current global gold standard of rigorous standardization has led to increasingly controlled environments. This growing disconnection between laboratory settings and real-world scenarios exacerbates the validation crisis. Rodent models have also revealed various environmental influences on drug use and its neural mechanisms, highlighting parallels with human behaviour and underscoring the importance of ecological relevance in behavioural research. Drawing inspiration from inquiries in ethology and evolutionary biology, I advocate for incorporating greater environmental complexity into animal models. In line with this idea, the neuroethological approach involves studying spontaneous behaviours in seminatural habitats while utilizing advanced technologies to monitor neural activity. Although this framework offers new insights into human neuroscience, it does not adequately capture the complex human conditions that lead to neuropsychiatric diseases. Therefore, preclinical research should prioritize understanding the environmental factors that shape human behaviour and neural architecture, integrating these insights into animal models. By emphasizing ecological relevance, we can achieve deeper insights into neuropsychiatric disorders and develop more effective treatment strategies. This approach highlights significant benefits for both scientific inquiry and ethical considerations. The controlled environment is a chimera; it is time to rethink our models. Here, I have chosen the prism of preclinical research on SUD to present, in a nonexhaustive manner, advances enabled by the use of rodent models, the crises faced by animal experimentation, the reflections and responses provided by laboratories, to finally propose rethinking our models around questions of ecological relevance, in order to improve both ethics and scientific quality. Although my discussion is illustrated by the situation in preclinical research on SUD, the observation drawn from it and the proposals made can extend to many other domains and species.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"61 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.16661","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}