Current research in neurobiology最新文献

{"title":"Neuromodulation of the anterior thalamus: Current approaches and opportunities for the future","authors":"Pooja Venkatesh,&nbsp;Cody Wolfe,&nbsp;Bradley Lega,&nbsp;Illustrations by Corbyn Beach","doi":"10.1016/j.crneur.2023.100109","DOIUrl":"https://doi.org/10.1016/j.crneur.2023.100109","url":null,"abstract":"<div><p>The role of thalamocortical circuits in memory has driven a recent burst of scholarship, especially in animal models. Investigating this circuitry in humans is more challenging. And yet, the development of new recording and stimulation technologies deployed for clinical indications has created novel opportunities for data collection to elucidate the cognitive roles of thalamic structures. These technologies include stereoelectroencephalography (SEEG), deep brain stimulation (DBS), and responsive neurostimulation (RNS), all of which have been applied to memory-related thalamic regions, specifically for seizure localization and treatment. This review seeks to summarize the existing applications of neuromodulation of the anterior thalamic nuclei (ANT) and highlight several devices and their capabilities that can allow cognitive researchers to design experiments to assay its functionality. Our goal is to introduce to investigators, who may not be familiar with these clinical devices, the capabilities, and limitations of these tools for understanding the neurophysiology of the ANT as it pertains to memory and other behaviors. We also briefly cover the targeting of other thalamic regions including the centromedian (CM) nucleus, dorsomedial (DM) nucleus, and pulvinar, with associated potential avenues of experimentation.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"5 ","pages":"Article 100109"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49774770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Publisher's announcement","authors":"Gail M. Rodney","doi":"10.1016/j.crneur.2023.100106","DOIUrl":"https://doi.org/10.1016/j.crneur.2023.100106","url":null,"abstract":"","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"5 ","pages":"Article 100106"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49774772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behavioral optogenetics in nonhuman primates; a psychological perspective","authors":"Arash Afraz","doi":"10.1016/j.crneur.2023.100101","DOIUrl":"https://doi.org/10.1016/j.crneur.2023.100101","url":null,"abstract":"<div><p>Optogenetics has been a promising and developing technology in systems neuroscience throughout the past decade. It has been difficult though to reliably establish the potential behavioral effects of optogenetic perturbation of the neural activity in nonhuman primates. This poses a challenge on the future of optogenetics in humans as the concepts and technology need to be developed in nonhuman primates first. Here, I briefly summarize the viable approaches taken to improve nonhuman primate behavioral optogenetics, then focus on one approach: improvements in the measurement of behavior. I bring examples from visual behavior and show how the choice of method of measurement might conceal large behavioral effects. I will then discuss the “cortical perturbation detection” task in detail as an example of a sensitive task that can record the behavioral effects of optogenetic cortical stimulation with high fidelity. Finally, encouraged by the rich scientific landscape ahead of behavioral optogenetics, I invite technology developers to improve the chronically implantable devices designed for simultaneous neural recording and optogenetic intervention in nonhuman primates.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"5 ","pages":"Article 100101"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49780848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficient viral expression of a chemogenetic receptor in the old-world monkey amygdala","authors":"Walter Lerchner ,&nbsp;Kiana Dash ,&nbsp;Deborah Rose ,&nbsp;Mark.A.G. Eldridge ,&nbsp;Kathryn.M. Rothenhoefer ,&nbsp;Xuefeng Yan ,&nbsp;Vincent.D. Costa ,&nbsp;Bruno Averbeck ,&nbsp;Barry.J. Richmond","doi":"10.1016/j.crneur.2023.100091","DOIUrl":"10.1016/j.crneur.2023.100091","url":null,"abstract":"<div><p>Genetically encoded synthetic receptors, such as the chemogenetic and optogenetic proteins, are powerful tools for functional brain studies in animals. In the primate brain, with its comparatively large, intricate anatomical structures, it can be challenging to express transgenes, such as the hM4Di chemogenetic receptor, in a defined anatomical structure with high penetrance. Here, we compare parameters for lentivirus vector injections in the rhesus monkey amygdala. We find that four injections of 20 μl, infused at 0.5 μl/min, can achieve neuronal hM4Di expression in 50–100% of neurons within a 60 mm³ volume, without observable damage from overexpression. Increasing the number of hM4Di_CFP lentivirus injections to up to 12 sites per hemisphere, resulted in 30%–40% neuronal coverage of the overall amygdala volume, with coverage reaching 60% in some subnuclei. Manganese Chloride was mixed with lentivirus and used as an MRI marker to verify targeting accuracy and correct unsuccessful injections in these experiments. In a separate monkey we visualized, in vivo<em>,</em> viral expression of the hM4Di receptor protein in the amygdala, using Positron Emission Tomography. Together, these data show efficient and verifiable expression of a chemogenetic receptor in old-world monkey amygdala.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"4 ","pages":"Article 100091"},"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/c2/29/main.PMC10313863.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9745783","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":"Unilateral caudate inactivation increases motor impulsivity in rhesus monkeys","authors":"Mark A.G. Eldridge ,&nbsp;Maya C. Smith ,&nbsp;Scott Hunter Oppler ,&nbsp;Jonah E. Pearl ,&nbsp;Jalene Y. Shim ,&nbsp;Walter Lerchner ,&nbsp;Barry J. Richmond","doi":"10.1016/j.crneur.2023.100085","DOIUrl":"10.1016/j.crneur.2023.100085","url":null,"abstract":"<div><p>Impulsivity, the tendency to react quickly and without consideration of consequences, is correlated with asymmetry in the volume of the caudate nucleus in human patients. In this study, we sought to determine whether the induction of functional asymmetry in the caudate nucleus of monkeys would produce phenomenologically comparable behavior. We found that unilateral suppression of the ventral caudate nucleus increases impulsive behavior in rhesus monkeys. Impulsivity was modeled by the subjects’ inability to maintain hold of a touch-sensitive bar until presentation of an imperative signal. Two methods were used to suppress activity in the caudate region. First, muscimol was locally infused. Second, a viral construct expressing the hM₄Di DREADD (designer receptor exclusively activated by designer drug) was injected at the same site. Clozapine N-oxide and deschloroclozapine activate the DREADD to suppress neuronal activity. Both methods of suppression, pharmacological and chemogenetic, increased the rate of early bar releases, a behavior we interpret to indicate impulsivity. Thus, we demonstrate a causal relationship between caudate asymmetry and impulsivity.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"4 ","pages":"Article 100085"},"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/b5/d5/main.PMC10313876.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9745785","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":"Optogenetic stimulation of the primary visual cortex drives activity in the visual association cortex","authors":"Michael Ortiz-Rios ,&nbsp;Beshoy Agayby ,&nbsp;Fabien Balezeau ,&nbsp;Marcus Haag ,&nbsp;Samy Rima ,&nbsp;Jaime Cadena-Valencia ,&nbsp;Michael C. Schmid","doi":"10.1016/j.crneur.2023.100087","DOIUrl":"10.1016/j.crneur.2023.100087","url":null,"abstract":"<div><p>Developing optogenetic methods for research in non-human primates (NHP) is important for translational neuroscience and for delineating brain function with unprecedented specificity. Here we assess, in macaque monkeys, the selectivity by which optogenetic stimulation of the primary visual cortex (V1) drives the local laminar and widespread cortical connectivity related to visual perception. Towards this end, we transfected neurons with light-sensitive channelrhodopsin in dorsal V1. fMRI revealed that optogenetic stimulation of V1 using blue light at 40 Hz increased functional activity in the visual association cortex, including areas V2/V3, V4, motion-sensitive area MT and frontal eye fields, although nonspecific heating and eye movement contributions to this effect could not be ruled out. Neurophysiology and immunohistochemistry analyses confirmed optogenetic modulation of spiking activity and opsin expression with the strongest expression in layer 4-B in V1. Stimulating this pathway during a perceptual decision task effectively elicited a phosphene percept in the receptive field of the stimulated neurons in one monkey. Taken together, our findings demonstrate the great potential of optogenetic methods to drive the large-scale cortical circuits of the primate brain with high functional and spatial specificity.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"4 ","pages":"Article 100087"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9745788","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":"Progranulin is an FMRP target that influences macroorchidism but not behaviour in a mouse model of Fragile X Syndrome","authors":"Benjamin Life ,&nbsp;Luis E.B. Bettio ,&nbsp;Ilse Gantois ,&nbsp;Brian R. Christie ,&nbsp;Blair R. Leavitt","doi":"10.1016/j.crneur.2023.100094","DOIUrl":"10.1016/j.crneur.2023.100094","url":null,"abstract":"<div><p>A growing body of evidence has implicated progranulin in neurodevelopment and indicated that aberrant progranulin expression may be involved in neurodevelopmental disease. Specifically, increased progranulin expression in the prefrontal cortex has been suggested to be pathologically relevant in male <em>Fmr1</em> knockout (<em>Fmr1</em> KO) mice, a mouse model of Fragile X Syndrome (FXS). Further investigation into the role of progranulin in FXS is warranted to determine if therapies that reduce progranulin expression represent a viable strategy for treating patients with FXS. Several key knowledge gaps remain. The mechanism of increased progranulin expression in <em>Fmr1</em> KO mice is poorly understood and the extent of progranulin's involvement in FXS-like phenotypes in <em>Fmr1</em> KO mice has been incompletely explored. To this end, we have performed a thorough characterization of progranulin expression in <em>Fmr1</em> KO mice. We find that the phenomenon of increased progranulin expression is post-translational and tissue-specific. We also demonstrate for the first time an association between progranulin mRNA and FMRP, suggesting that progranulin mRNA is an FMRP target. Subsequently, we show that progranulin over-expression in <em>Fmr1</em> wild-type mice causes reduced repetitive behaviour engagement in females and mild hyperactivity in males but is largely insufficient to recapitulate FXS-associated behavioural, morphological, and electrophysiological abnormalities. Lastly, we determine that genetic reduction of progranulin expression on an <em>Fmr1</em> KO background reduces macroorchidism but does not alter other FXS-associated behaviours or biochemical phenotypes.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"5 ","pages":"Article 100094"},"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/b7/45/main.PMC10319828.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9796670","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":"Characterisation of functional deficits induced by AAV overexpression of alpha-synuclein in rats","authors":"F. Gubinelli ,&nbsp;L. Sarauskyte ,&nbsp;C. Venuti ,&nbsp;I. Kulacz ,&nbsp;G. Cazzolla ,&nbsp;M. Negrini ,&nbsp;D. Anwer ,&nbsp;I. Vecchio ,&nbsp;F. Jakobs ,&nbsp;F.P. Manfredsson ,&nbsp;M. Davidsson ,&nbsp;A. Heuer","doi":"10.1016/j.crneur.2022.100065","DOIUrl":"10.1016/j.crneur.2022.100065","url":null,"abstract":"<div><h3>Background</h3><p>In the last decades different preclinical animal models of Parkinson's disease (PD) have been generated, aiming to mimic the progressive neuronal loss of midbrain dopaminergic (DA) cells as well as motor and non-motor impairment. Among all the available models, AAV-based models of human alpha-synuclein (h-aSYN) overexpression are promising tools for investigation of disease progression and therapeutic interventions.</p></div><div><h3>Objectives</h3><p>The goal with this work was to characterise the impairment in motor and non-motor domains following nigrostriatal overexpression of h-aSYN and correlate the behavioural deficits with histological assessment of associated pathology.</p></div><div><h3>Methods</h3><p>Intranigral injection of an AAV9 expressing h-aSYN was compared with untreated animals, 6-OHDA and AAV9 expressing either no transgene or GFP. The animals were assessed on a series of simple and complex behavioural tasks probing motor and non-motor domains. Post-mortem neuropathology was analysed using immunohistochemical methods.</p></div><div><h3>Results</h3><p>Overexpression of h-aSYN led to progressive degeneration of DA neurons of the SN and axonal terminals in the striatum (STR). We observed extensive nigral and striatal pathology, resembling that of human PD brain, as well as the development of stable progressive deficit in simple motor tasks and in non-motor domains such as deficits in motivation and lateralised neglect.</p></div><div><h3>Conclusions</h3><p>In the present work we characterized a rat model of PD that closely resembles human PD pathology at the histological and behavioural level. The correlation of cell loss with behavioural performance enables the selection of rats which can be used in neuroprotective or neurorestorative therapies.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"4 ","pages":"Article 100065"},"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/06/33/main.PMC9827042.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9899919","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":"Altered pattern separation in Goto-Kakizaki rats","authors":"Chelsey C. Damphousse,&nbsp;Jaclyn K. Medeiros,&nbsp;Nicole E. Micks,&nbsp;Diano F. Marrone","doi":"10.1016/j.crneur.2023.100082","DOIUrl":"10.1016/j.crneur.2023.100082","url":null,"abstract":"<div><p>Type 2 diabetes mellitus has steadily increased in prevalence over the past five decades. Among the health risks associated with this disorder are cognitive decline and are increased risk of developing dementia. To further investigate the link between diabetes and cognition, here we test memory performance and hippocampal function in the Goto-Kakizaki (GK) rat, a robust model of diabetes. Relative to age-matched Wistar rats, GK rats show impairments in a conjunctive memory task that requires discriminating objects not only on the basis of their physical characteristics, but also on the basis of where and when they were last seen. Concomitant to these deficits are changes in the pattern of expression of <em>Egr1</em> (an immediate-early gene critical for memory) in dentate gyrus granule cells, consistent with dentate hypoactivity leading to unstable hippocampal representations. These data support the hypothesis that diabetes confers a phenotype of accelerated senescence on the hippocampus, and help to link this disorder with changes in hippocampal circuits.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"4 ","pages":"Article 100082"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10123129","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":"Δ9-Tetrahydrocannabinol does not upregulate an aversive dopamine receptor mechanism in adolescent brain unlike in adults","authors":"Marie-Eve Di Raddo ,&nbsp;Marija Milenkovic ,&nbsp;Meenalochani Sivasubramanian ,&nbsp;Ahmed Hasbi ,&nbsp;Jack Bergman ,&nbsp;Sarah Withey ,&nbsp;Bertha K. Madras ,&nbsp;Susan R. George","doi":"10.1016/j.crneur.2023.100107","DOIUrl":"10.1016/j.crneur.2023.100107","url":null,"abstract":"<div><p>Earlier age of cannabis usage poses higher risk of Cannabis Use Disorder and adverse consequences, such as addiction, anxiety, dysphoria, psychosis, largely attributed to its principal psychoactive component, Δ9-tetrahydrocannabinol (THC) and altered dopaminergic function. As dopamine D1-D2 receptor heteromer activation causes anxiety and anhedonia, this signaling complex was postulated to contribute to THC-induced affective symptoms. To investigate this, we administered THC repeatedly to adolescent monkeys and adolescent or adult rats. Drug-naïve adolescent rat had lower striatal densities of D1-D2 heteromer compared to adult rat. Repeated administration of THC to adolescent rat or adolescent monkey did not alter D1-D2 heteromer expression in nucleus accumbens or dorsal striatum but upregulated it in adult rat. Behaviourally, THC-treated adult, but not adolescent rat manifested anxiety and anhedonia-like behaviour, with elevated composite negative emotionality scores that correlated with striatal D1-D2 density. THC modified downstream markers of D1-D2 activation in adult, but not adolescent striatum. THC administered with cannabidiol did not alter D1-D2 expression. In adult rat, co-administration of CB1 receptor (CB1R) inverse agonist with THC attenuated D1-D2 upregulation, implicating cannabinoids in the regulation of striatal D1-D2 heteromer expression. THC exposure revealed an adaptable age-specific, anxiogenic, anti-reward mechanism operant in adult striatum but deficient in adolescent rat and monkey striatum that may confer increased sensitivity to THC reward in adolescence while limiting its negative effects, thus promoting continued use and increasing vulnerability to long-term adverse cannabis effects.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"5 ","pages":"Article 100107"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44535835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}