{"title":"Introducing individual sentience profiles in nonhuman primate neuroscience research","authors":"Angelica Kaufmann","doi":"10.1016/j.crneur.2023.100104","DOIUrl":"10.1016/j.crneur.2023.100104","url":null,"abstract":"<div><p>The Animal Research Declaration is committed to establishing cohesive and rigorous ethical standards to safeguard the welfare of nonhuman primates (NHPs) engaged in neuroscience research (Petkov et al., 2022 this issue). As part of this mission, there is an expanding dialogue amongst neuroscientists, philosophers, and policymakers, that is centred on diverse aspects of animal welfare and scientific practice. This paper emphasises the necessity of integrating the assessment of animal sentience into the declaration. Animal sentience, in this context, refers to the recognized capacity that animals have for various kinds of subjective experience, with an associated positive or negative valence (Browning and Birch, 2022). Accordingly, NHP neuroscience researchers should work toward instituting a standardised approach for evaluating what can be termed \"individual sentience profiles,\" representing the unique manner in which an individual NHP experiences specific events or environments. The adoption of this novel parameter would serve a triad of indispensable purposes: enhancing NHP welfare throughout research involvement, elevating the quality of life for NHPs in captivity, and refining the calibre of research outcomes.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"5 ","pages":"Article 100104"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b0/94/main.PMC10415712.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9989967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alison R. Weiss , William A. Liguore , Kristin Brandon , Xiaojie Wang , Zheng Liu , Christopher D. Kroenke , Jodi L. McBride
{"title":"Alterations of fractional anisotropy throughout cortico-basal ganglia gray matter in a macaque model of Huntington’s Disease","authors":"Alison R. Weiss , William A. Liguore , Kristin Brandon , Xiaojie Wang , Zheng Liu , Christopher D. Kroenke , Jodi L. McBride","doi":"10.1016/j.crneur.2023.100090","DOIUrl":"10.1016/j.crneur.2023.100090","url":null,"abstract":"<div><p>We recently generated a nonhuman primate (NHP) model of the neurodegenerative disorder Huntington's disease (HD) using adeno-associated viral vectors to express a fragment of mutant HTT protein (mHTT) throughout the cortico-basal ganglia circuit. Previous work by our group established that mHTT-treated NHPs exhibit progressive motor and cognitive phenotypes which are accompanied by mild volumetric reductions of cortical-basal ganglia structures and reduced fractional anisotropy (FA) in the white matter fiber pathways interconnecting these regions, mirroring findings observed in early-stage HD patients. Given the mild structural atrophy observed in cortical and sub-cortical gray matter regions characterized in this model using tensor-based morphometry, the current study sought to query potential microstructural alterations in the same gray matter regions using diffusion tensor imaging (DTI), to define early biomarkers of neurodegenerative processes in this model. Here, we report that mHTT-treated NHPs exhibit significant microstructural changes in several cortical and subcortical brain regions that comprise the cortico-basal ganglia circuit; with increased FA in the putamen and globus pallidus and decreased FA in the caudate nucleus and several cortical regions. DTI measures also correlated with motor and cognitive deficits such that animals with increased basal ganglia FA, and decreased cortical FA, had more severe motor and cognitive impairment. These data highlight the functional implications of microstructural changes in the cortico-basal ganglia circuit in early-stage HD.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"4 ","pages":"Article 100090"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/de/c6/main.PMC10313883.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10001442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maximilian Kaffes , Lea Rabe , Armin Rudolph , Johannes Rentzsch , Andres H. Neuhaus , Christina Hofmann-Shen
{"title":"Impact of emotional valence on mismatch negativity in the course of cortical face processing","authors":"Maximilian Kaffes , Lea Rabe , Armin Rudolph , Johannes Rentzsch , Andres H. Neuhaus , Christina Hofmann-Shen","doi":"10.1016/j.crneur.2023.100078","DOIUrl":"10.1016/j.crneur.2023.100078","url":null,"abstract":"<div><p>Various aspects of cortical face processing have been studied by assessing event related potentials (ERP). It has been described in the literature that mismatch negativity (MMN), a well-studied ERP, is not only modulated by sensory features but also emotional valence. However, the exact impact of emotion on the temporo-spatial profile of visual MMN during face processing remains inconsistent. By employing a sequential oddball paradigm using both neutral and emotional deviants, we were able to differentiate two distinct vMMN subcomponents. While an early subcomponent at 150–250 ms is elicited by emotional salient facial stimuli, the later subcomponent at 250–400 ms seems to reflect the detection of regularity violations in facial recognition per se, unaffected by emotional salience. Our results suggest that emotional valence is encoded in vMMN signal strength at an early stage of facial processing. Furthermore, we assume that of facial processing consists of temporo-spatially distinct, partially overlapping levels concerning different facial aspects.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"4 ","pages":"Article 100078"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a4/a3/main.PMC10011816.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9132709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Devin H. Kehoe , Lukas Schießer , Hassaan Malik , Mazyar Fallah
{"title":"Motion distractors perturb saccade programming later in time than static distractors","authors":"Devin H. Kehoe , Lukas Schießer , Hassaan Malik , Mazyar Fallah","doi":"10.1016/j.crneur.2023.100092","DOIUrl":"10.1016/j.crneur.2023.100092","url":null,"abstract":"<div><p>The mechanism that reweights oculomotor vectors based on visual features is unclear. However, the latency of oculomotor visual activations gives insight into their antecedent featural processing. We compared the oculomotor processing time course of grayscale, task-irrelevant static and motion distractors during target selection by continuously measuring a battery of human saccadic behavioral metrics as a function of time after distractor onset. The motion direction was towards or away from the target and the motion speed was fast or slow. We compared static and motion distractors and observed that both distractors elicited curved saccades and shifted endpoints at short latencies (∼25 ms). After 50 ms, saccade trajectory biasing elicited by motion distractors lagged static distractor trajectory biasing by 10 ms. There were no such latency differences between distractor motion directions or motion speeds. This pattern suggests that additional processing of motion stimuli occurred prior to the propagation of visual information into the oculomotor system. We examined the interaction of distractor processing time (DPT) with two additional factors: saccadic reaction time (SRT) and saccadic amplitude. Shorter SRTs were associated with shorter DPT latencies of biased saccade trajectories. Both SRT and saccadic amplitude were associated with the magnitude of saccade trajectory biases.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"4 ","pages":"Article 100092"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/95/7d/main.PMC10313862.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9745782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rb deficiency, neuronal survival and neurodegeneration: In search of the perfect mouse model","authors":"Saad Omais, Yara E. El Atie, Noël Ghanem","doi":"10.1016/j.crneur.2023.100074","DOIUrl":"10.1016/j.crneur.2023.100074","url":null,"abstract":"<div><p>Three decades following the introduction of the first Rb knockout (KO) mouse model, the role of this critical protein in regulating brain development during embryogenesis and beyond remains a major scientific interest. Rb is a tumor suppressor gene known as the master regulator of the G1/S checkpoint and control of cell cycle progression in stem and progenitor cells, but also their differentiated progeny. Here, we review the recent literature about the various Rb conditional Knockout (cKO) and inducible Knockout (iKO) models studied thus far, highlighting how findings should always be interpreted in light of the model and context under inquiry especially when studying the role of Rb in neuronal survival. There is indeed evidence of age-specific, cell type-specific and region-specific effects following Rb KO in the embryonic and the adult mouse brain. In terms of modeling neurodegenerative processes in human diseases, we discuss cell cycle re-entry (CCE) as a candidate mechanism underlying the increased vulnerability of Rb-deficient neurons to cell death. Notably, mouse models may limit the extent to which CCE due to Rb inactivation can mimic the pathological course of these disorders, such as Alzheimer's disease. These remarks ought to be considered in future research when studying the consequences of Rb inactivation on neuronal generation and survival in rodents and their corresponding clinical significance in humans.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"4 ","pages":"Article 100074"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/df/82/main.PMC9869410.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10628283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unraveling the links between neurodegeneration and Epstein-Barr virus-mediated cell cycle dysregulation","authors":"Deeksha Tiwari , Nitish Mittal , Hem Chandra Jha","doi":"10.1016/j.crneur.2022.100046","DOIUrl":"10.1016/j.crneur.2022.100046","url":null,"abstract":"<div><p>The Epstein-Barr virus is a well-known cell cycle modulator. To establish successful infection in the host, EBV alters the cell cycle at multiple steps via antigens such as EBNAs, LMPs, and certain other EBV-encoded transcripts. Interestingly, several recent studies have indicated the possibility of EBV's neurotrophic potential. However, the effects and outcomes of EBV infection in the CNS are under-explored. Additionally, more and more epidemiological evidence implicates the cell-cycle dysregulation in neurodegeneration. Numerous hypotheses which describe the triggers that force post-mitotic neurons to re-enter the cell cycle are prevalent. Apart from the known genetic and epigenetic factors responsible, several reports have shown the association of microbial infections with neurodegenerative pathology. Although, studies implicating the herpesvirus family members in neurodegeneration exist, the involvement of Epstein-Barr virus (EBV), in particular, is under-evaluated. Interestingly, a few clinical studies have reported patients of AD or PD to be seropositive for EBV. Based on the findings mentioned above, in this review, we propose that EBV infection in neurons could drive it towards neurodegeneration through dysregulation of cell-cycle events and induction of apoptosis.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"3 ","pages":"Article 100046"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f1/9a/main.PMC9846474.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9184389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
James Auta , Andrea Locci , Alessandro Guidotti , John M. Davis , Hongxin Dong
{"title":"Sex-dependent sensitivity to positive allosteric modulation of GABA action in an APP knock-in mouse model of Alzheimer's disease: Potential epigenetic regulation","authors":"James Auta , Andrea Locci , Alessandro Guidotti , John M. Davis , Hongxin Dong","doi":"10.1016/j.crneur.2021.100025","DOIUrl":"10.1016/j.crneur.2021.100025","url":null,"abstract":"<div><p>Conflicting evidence suggest that perturbations of GABAergic neurotransmission play crucial roles in disrupting cortical neuronal network oscillations, memory, and cognitive deficits in Alzheimer's disease (AD). However, the role and impact of sex differences on GABAergic transmission in AD are not well understood. Using an APP knock-in mouse model of AD, APP<sup>NLGF</sup> mice, we studied the effects of acute diazepam administration on memory and anxiety-like behavior to unveil sex-dependent dysregulation of GABAergic neurotransmission. We also examined sex differences in GABA<sub>A</sub> receptor subunit mRNA and protein expression and the role of epigenetic regulation in hippocampus of APP<sup>NLGF</sup> mice. We found that diazepam elicited dose-dependent suppression of locomotion in wildtype and APP<sup>NLGF</sup> mice. However, a low dose, which had no significant effect in both male and female wildtype as well as female APP<sup>NLGF</sup> mice, significantly suppressed locomotion in male APP<sup>NLGF</sup> mice. Furthermore, this low dose of diazepam was more efficacious at eliciting anxiolytic-like effects in male than female APP<sup>NLGF</sup> mice. The same low dose of diazepam disrupted recognition memory exclusively in male APP<sup>NLGF</sup> mice. Biochemical analyses revealed that hippocampal α1 and α5 GABA<sub>A</sub> receptor subunits mRNA and protein expression were significantly higher in male than female APP<sup>NLGF</sup> mice and were regulated by histone H3 tri-methylation (H3K4me3) but not histone H3 acetylation. The higher sensitivity of APP<sup>NLGF</sup> males to diazepam-induced behavioral effects may potentially be due to epigenetic-dependent upregulation of hippocampal α1 and α5 GABA<sub>A</sub> receptor subunits expression compared to female APP<sup>NLGF</sup> mice. These findings suggest that dysregulation of GABAergic neurotransmission plays a significant role in memory and affective behavior, particularly in male APP<sup>NLGF</sup> mice.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"3 ","pages":"Article 100025"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/18/0f/main.PMC9743067.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10361735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paul Alexander Bloom PhD , Monica Kim Ngan Thieu PhD , Niall Bolger PhD
{"title":"Commentary on Unnecessary reliance on multilevel modelling to analyse nested data in neuroscience: When a traditional summary-statistics approach suffices","authors":"Paul Alexander Bloom PhD , Monica Kim Ngan Thieu PhD , Niall Bolger PhD","doi":"10.1016/j.crneur.2022.100041","DOIUrl":"10.1016/j.crneur.2022.100041","url":null,"abstract":"","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"3 ","pages":"Article 100041"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9846465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10581802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Agnese Minuti, Francesca Brufani, Giulia Menculini, Patrizia Moretti, Alfonso Tortorella
{"title":"The complex relationship between gut microbiota dysregulation and mood disorders: A narrative review","authors":"Agnese Minuti, Francesca Brufani, Giulia Menculini, Patrizia Moretti, Alfonso Tortorella","doi":"10.1016/j.crneur.2022.100044","DOIUrl":"10.1016/j.crneur.2022.100044","url":null,"abstract":"<div><p>Gut microbiota regulates neurotransmission, neurogenesis, neuroinflammation, and neuroendocrine signaling. The aim of the present review is to analyze the literature concerning gut microbiota dysregulation and mood symptoms, with the specific hypothesis that such alterations play a role in the onset of mood disorders. Here, in fact, we review recent research focusing on how gut microbiota dysregulation influences the onset of mood disorders and on possible pathophysiological mechanisms involved in this interaction. We pay specific attention to the relationship between gut microbiota dysregulation and inflammatory state, Th17 differentiation, neuroactive factors, and TRP metabolism. The association between gut microbiota dysregulation and mood disorders is critically analyzed under a clinical point of view, also focusing on the emergence of mood symptoms in the context of medical conditions.</p><p>These latter correlations may enable an interdisciplinary perspective in the clinical approach to such symptoms, as well as new treatment strategies, such as nutritional interventions, psychobiotics, antibiotics, as well as fecal microbiota transplantation.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"3 ","pages":"Article 100044"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ea/64/main.PMC9846469.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10586916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An active inference model of conscious access: How cognitive action selection reconciles the results of report and no-report paradigms","authors":"Christopher J. Whyte , Jakob Hohwy , Ryan Smith","doi":"10.1016/j.crneur.2022.100036","DOIUrl":"10.1016/j.crneur.2022.100036","url":null,"abstract":"<div><p>Cognitive theories of consciousness, such as global workspace theory and higher-order theories, posit that frontoparietal circuits play a crucial role in conscious access. However, recent studies using no-report paradigms have posed a challenge to cognitive theories by demonstrating conscious accessibility in the apparent absence of prefrontal cortex (PFC) activation. To address this challenge, this paper presents a computational model of conscious access, based upon active inference, that treats working memory gating as a cognitive action. We simulate a visual masking task and show that late P3b-like event-related potentials (ERPs), and increased PFC activity, are induced by the working memory demands of self-report generation. When reporting demands are removed, these late ERPs vanish and PFC activity is reduced. These results therefore reproduce, and potentially explain, results from no-report paradigms. However, even without reporting demands, our model shows that simulated PFC activity on visible stimulus trials still crosses the threshold for reportability – maintaining the link between PFC and conscious access. Therefore, our simulations show that evidence provided by no-report paradigms does not necessarily contradict cognitive theories of consciousness.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"3 ","pages":"Article 100036"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2b/2b/main.PMC9593308.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9152997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}