Journal of neurogenetics最新文献

{"title":"The light-activated TRP channel: the founding member of the TRP channel superfamily.","authors":"Baruch Minke,&nbsp;William L Pak","doi":"10.1080/01677063.2022.2121824","DOIUrl":"https://doi.org/10.1080/01677063.2022.2121824","url":null,"abstract":"<p><p>The <i>Drosophila</i> light-activated Transient Receptor Potential (TRP) channel is the founding member of a large and diverse family of channel proteins. The <i>Drosophila</i> TRP (dTRP) channel, which generates the electrical response to light has been investigated in a great detail two decades before the first mammalian TRP channel was discovered. Thus, dTRP is unique among members of the TRP channel superfamily because its physiological role and the enzymatic cascade underlying its activation are established. In this article we outline the research leading to elucidation of dTRP as the light activated channel and focus on a major physiological property of the dTRP channel, which is indirect activation via a cascade of enzymatic reactions. These detailed pioneering studies, based on the genetic dissection approach, revealed that light activation of the <i>Drosophila</i> TRP channel is mediated by G-Protein-Coupled Receptor (GPCR)-dependent enzymatic cascade, in which phospholipase C β (PLC) is a crucial component. This physiological mechanism of <i>Drosophila</i> TRP channel activation was later found in mammalian TRPC channels. However, the initial studies on the mammalian TRPV1 channel indicated that it is activated directly by capsaicin, low pH and hot temperature (>42 °C). This mechanism of activation was apparently at odds with the activation mechanism of the TRPC channels in general and the <i>Drosophila</i> light activated TRP/TRPL channels in particular, which are target of a GPCR-activated PLC cascade. Subsequent studies have indicated that under physiological conditions TRPV1 is also target of a GPCR-activated PLC cascade in the generation of inflammatory pain. The <i>Drosophila</i> light-activated TRP channel is still a useful experimental paradigm because its physiological function as the light-activated channel is known, powerful genetic techniques can be applied to its further analysis, and signaling molecules involved in the activation of these channels are available.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"36 2-3","pages":"55-64"},"PeriodicalIF":1.9,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10709524","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":"The force-from-lipid principle and its origin, a '<i>what is true for E. coli is true for the elephant'</i> refrain.","authors":"Boris Martinac,&nbsp;Ching Kung","doi":"10.1080/01677063.2022.2097674","DOIUrl":"https://doi.org/10.1080/01677063.2022.2097674","url":null,"abstract":"<p><p>The force-from-lipid (FFL) principle states that it is the lateral stretch force from the lipid membrane that ultimately opens mechanosensitive (MS) channels, not the external tether nor the internal cytoskeleton. Piezo channels for certain touch or proprioception and the hair-cell channels for hearing or balance apparently obey this principle, which is based on the idea that the lipid bilayer is an amphipathic compartment with a distinct internal force-distribution profile. Physical stretch or insertion of chemical impurities alters this profile, driving channel shape change to conform to the new environment. Thus, FFL governs all dynamic proteins embedded in membrane, including Kv's and TRPs. This article retraces the humble origin of the FFL concept. <i>Paramecium</i> research first created the mind set and the resources to electrically explore other microbial membranes. Patch clamp revealed MS-channel activities from yeast and <i>E. coli</i> spheroplasts. Despite formidable obstacles against interdisciplinary research, the <i>E. coli</i> MS-channel protein, MscL, was purified through fractionation by following its activity, much like enzyme purification. Reconstituted into a simple lipid bilayer, pure MscL retains mechanosensitivity, thus firmly establishing the FFL principle in 1994. The relatively simple MscL and its functional cousin MscS soon became ideal models for detailed analyses. Like the DNA-RNA-protein 'central dogma' or ATP synthesis, FFL is a fundamental principle, which appeared early in evolution, retained in all cellular life forms, and is expected to contribute to future molecular research on sensations, homeostasis, and embryonic development.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"36 2-3","pages":"44-54"},"PeriodicalIF":1.9,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10707764","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":"Abnormal larval neuromuscular junction morphology and physiology in <i>Drosophila</i> prickle isoform mutants with known axonal transport defects and adult seizure behavior.","authors":"Atsushi Ueda,&nbsp;Tristan C D G O'Harrow,&nbsp;Xiaomin Xing,&nbsp;Salleh Ehaideb,&nbsp;J Robert Manak,&nbsp;Chun-Fang Wu","doi":"10.1080/01677063.2022.2093353","DOIUrl":"https://doi.org/10.1080/01677063.2022.2093353","url":null,"abstract":"<p><p>Previous studies have demonstrated the striking mutational effects of the <i>Drosophila</i> planar cell polarity gene <i>prickle (pk)</i> on larval motor axon microtubule-mediated vesicular transport and on adult epileptic behavior associated with neuronal circuit hyperexcitability. Mutant alleles of the <i>prickle</i>-<i>prickle</i> (<i>pk^pk</i>) and <i>prickle</i>-<i>spiny-legs</i> (<i>pk^sple</i>) isoforms (hereafter referred to as <i>pk</i> and <i>sple</i> alleles, respectively) exhibit differential phenotypes. While both <i>pk</i> and <i>sple</i> affect larval motor axon transport, only <i>sple</i> confers motor circuit and behavior hyperexcitability. However, mutations in the two isoforms apparently counteract to ameliorate adult motor circuit and behavioral hyperexcitability in heteroallelic <i>pk^pk/pk^spl</i>^e flies. We have further investigated the consequences of altered axonal transport in the development and function of the larval neuromuscular junction (NMJ). We uncovered robust dominant phenotypes in both <i>pk</i> and <i>sple</i> alleles, including synaptic terminal overgrowth (as revealed by anti-HRP and -Dlg immunostaining) and poor vesicle release synchronicity (as indicated by synaptic bouton focal recording). However, we observed recessive alteration of synaptic transmission only in <i>pk/pk</i> larvae, i.e. increased excitatory junctional potential (EJP) amplitude in <i>pk/pk</i> but not in <i>pk</i>/+ or <i>sple</i>/<i>sple</i>. Interestingly, for motor terminal excitability sustained by presynaptic Ca²⁺ channels, both <i>pk</i> and <i>sple</i> exerted strong effects to produce prolonged depolarization. Notably, only <i>sple</i> acted dominantly whereas <i>pk</i>/+ appeared normal, but was able to suppress the <i>sple</i> phenotypes, i.e. <i>pk/sple</i> appeared normal. Our observations contrast the differential roles of the <i>pk</i> and <i>sple</i> isoforms and highlight their distinct, variable phenotypic expression in the various structural and functional aspects of the larval NMJ.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"36 2-3","pages":"65-73"},"PeriodicalIF":1.9,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10689881","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":"Abnormalities of neural stem cells in Lesch-Nyhan disease.","authors":"Ashok R Dinasarapu, Diane J Sutcliffe, Fatemeh Seifar, Jasper E Visser, H A Jinnah","doi":"10.1080/01677063.2022.2129632","DOIUrl":"10.1080/01677063.2022.2129632","url":null,"abstract":"<p><p>Lesch-Nyhan disease (LND) is a neurodevelopmental disorder caused by variants in the <i>HPRT1</i> gene, which encodes the enzyme hypoxanthine-guanine phosphoribosyl transferase (HGprt). HGprt deficiency provokes numerous metabolic changes which vary among different cell types, making it unclear which changes are most relevant for abnormal neural development. To begin to elucidate the consequences of HGprt deficiency for developing human neurons, neural stem cells (NSCs) were prepared from 6 induced pluripotent stem cell (iPSC) lines from individuals with LND and compared to 6 normal healthy controls. For all 12 lines, gene expression profiles were determined by RNA-seq and protein expression profiles were determined by shotgun proteomics. The LND lines revealed significant changes in expression of multiple genes and proteins. There was little overlap in findings between iPSCs and NSCs, confirming the impact of HGprt deficiency depends on cell type. For NSCs, gene expression studies pointed towards abnormalities in WNT signaling, which is known to play a role in neural development. Protein expression studies pointed to abnormalities in the mitochondrial F₀F₁ ATPase, which plays a role in maintaining cellular energy. These studies point to some mechanisms that may be responsible for abnormal neural development in LND.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"36 2-3","pages":"81-87"},"PeriodicalIF":1.9,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9847586/pdf/nihms-1862228.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9464385","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":"The origins of the force-from-lipid principle and the founding member of the TRP channel superfamily.","authors":"Chun-Fang Wu","doi":"10.1080/01677063.2022.2132104","DOIUrl":"https://doi.org/10.1080/01677063.2022.2132104","url":null,"abstract":"The 2021 Nobel Prize in Medicine and Physiology recognized the seminal work of David Julius, who established the temperature and pain sensory mechanisms based on the TRPV channel, and Ardem Patapoutian, who resolved the stretch activation mechanism for touch and proprietary sensation via Piezo channels. We are fortunate and proud to publish a special section on the force-from-lipid principle underlining Piezo channel activation and the origin of the first TRP channel, prepared by the pioneers who initiated the early work that led to the discoveries (Martinac & Kung, 2022; Minke & Pak, 2022). Professors Baruch Minke and William Pak recount the story of their early endeavor to reveal the phototransduction process mediated by the TRP channel in the fruit fly Drosophila. This light-sensitive TRP channel is now recognized as the founding member of the TRP channel superfamily, which encompasses a large category of channels underpinning different sensory mechanisms, including visual, auditory, thermal, and mechanosensory transduction. The functioning of Piezo channels turns out to be based on the same force-from-lipid principle, originating from lipid membrane lateral force without involving any cytoskeletal or cell adhesion molecules. As professors Ching Kung and Boris Martinac recount in their article, the initial finding actually originated from studies on a special strain of giant E. coli. Indeed, ‘what is true for E. coli is true for the elephant’.","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"36 2-3","pages":"43"},"PeriodicalIF":1.9,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10709528","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":"lncRNA XIST induces Aβ accumulation and neuroinflammation by the epigenetic repression of NEP in Alzheimer's disease.","authors":"Xi-Wu Yan,&nbsp;Huai-Jun Liu,&nbsp;Yu-Xing Hong,&nbsp;Ting Meng,&nbsp;Jun Du,&nbsp;Cheng Chang","doi":"10.1080/01677063.2022.2028784","DOIUrl":"https://doi.org/10.1080/01677063.2022.2028784","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the leading cause of dementia globally, but effective treatment is lacking. We aimed to explore lncRNA XIST role in AD and the mechanisms involved in the effect of changes in lncRNA XIST on the expression of Aβ-degrading enzymes. The mouse model of AD and the cell model induced by Aβ were established. LncRNA XIST, IDE, NEP, Plasmin, ACE, EZH2 expressions and distribution of XIST in the nucleus and cytoplasm were detected by qRT-PCR. Inflammatory cytokines IL-6, IL-1β, TNFα, IL-8, and Aβ42 levels were detected by ELISA. TUNEL was used to measure brain tissue damage. Cell proliferation was detected by CCK-8 assay. Flow cytometry detected cell apoptosis. RIP validated the combination of XIST and EZH2. ChIP verified that XIST recruits EZH2 to mediate enrichment of HEK27me3 in the NEP promoter region. The protein expression in brain tissues and cells was detected by Western blot. The expression of lncRNA XIST was increased in AD mice and cell models. Inflammation and injury of nerve cells occurred in AD mice and cell models. The knockdown of lncRNA XIST alleviated Aβ-induced neuronal inflammation and damage. LncRNA XIST affected the expression of Aβ-degrading enzyme NEP, and lncRNA XIST was negatively correlated with NEP expression in AD mice. LncRNA XIST regulated NEP expression partly through epigenetic regulation by binding with EZH2. LncRNA XIST mediated neuronal inflammation and injury through epigenetic regulation of NEP. Overall, our study found that lncRNA XIST induced Aβ accumulation and neuroinflammation by the epigenetic repression of NEP in AD.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"36 1","pages":"11-20"},"PeriodicalIF":1.9,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39751382","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":"Reduction of the α-synuclein expression promotes slowing down early neuropathology development in the Drosophila model of Parkinson’s disease","authors":"Ilia M Golomidov, Evgenia M. Latypova, E. Ryabova, O. Bolshakova, A. Komissarov, S. Sarantseva","doi":"10.1080/01677063.2022.2064462","DOIUrl":"https://doi.org/10.1080/01677063.2022.2064462","url":null,"abstract":"Abstract Parkinson’s disease (PD) is a neurodegenerative disease characterised by the formation of Lewy bodies and progressive loss of dopaminergic (DA) neurons in the substantia nigra. Lewy bodies mainly consist of α-synuclein, which plays a critical role in the pathophysiology of PD. The α-synuclein is encoded by the SNCA gene and is the first identified gene associated with hereditary PD. Currently, there are at least six disease-associated mutations in α-synuclein that cause dominantly inherited familial forms of PD. Targeted expression of human SNCA.WT/SNCA.A30P/SNCA.A53T gene in Drosophila melanogaster over specific times employing a temperature-dependent UAS/GAL4 – GAL80 system allows for the evaluation of neurodegenerative processes. In this study, SNCA was expressed only in the adult stage of Drosophila development for 1 or 2 weeks, followed by repression of gene expression for the rest of the fly’s life. It was demonstrated that the level of pathology significantly depends on the duration of α-synuclein expression. SNCA gene expression over a longer period of time caused the death of DA neurons, decreased levels of dopamine and locomotor ability. In this case, the observed neurodegenerative processes correlated with the accumulation of α-synuclein in the Drosophila brain. Importantly, repression of α-synuclein expression led to elimination of the soluble protein fraction, in contrast to the insoluble fraction. No further significant development of characteristic signs of pathology was observed after the α-synuclein expression was blocked. Thus, we suggest that reduction of α-synuclein expression alone contributes to slowing down the development of PD-like symptoms.","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"36 1","pages":"1 - 10"},"PeriodicalIF":1.9,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42383867","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":"LncRNA GAS5 promotes epilepsy progression through the epigenetic repression of miR-219, in turn affecting CaMKIIγ/NMDAR pathway","authors":"Chen-sheng Zhao, Dong-xing Liu, Yanping Fan, Jian-kun Wu","doi":"10.1080/01677063.2022.2067536","DOIUrl":"https://doi.org/10.1080/01677063.2022.2067536","url":null,"abstract":"Abstract It has been widely reported that dysregulated long-chain noncoding RNAs (lncRNAs) are closely associated with epilepsy. This study aimed to probe the function of lncRNA growth arrest-specific 5 (GAS5), microRNA (miR)-219 and Calmodulin-dependent protein kinase II (CaMKII)γ/N-methyl-D-aspartate receptor (NMDAR) pathway in epilepsy. Epileptic cell and animal models were constructed using magnesium deficiency treatment and diazepam injection, respectively. GAS5 and miR-219 expressions in epileptic cell and animal models were determined using qRT-PCR assay. The protein levels of CaMKIIγ, NMDAR and apoptosis-related proteins levels were assessed by western blot. Cell counting kit-8 (CCK-8) assay was employed to determine cell proliferation. Besides, TNFα, IL-1β, IL-6 and IL-8 levels were analyzed using enzyme-linked immunosorbent assay (ELISA). Furthermore, cell apoptosis was evaluated using TUNEL staining and flow cytometric analysis. Finally, the binding relationship between GAS5 and EZH2 was verified using RIP and ChIP assay. Our results revealed that GAS5 was markedly upregulated in epileptic cell and animal models, while miR-219 was down-regulated. GAS5 knockdown dramatically increased cell proliferation of epileptic cells, whereas suppressed inflammation and the apoptosis. Furthermore, our results showed that GAS5 epigenetically suppressed transcriptional miR-219 expression via binding to EZH2. miR-219 mimics significantly enhanced cell proliferation of epileptic cells, while inhibited inflammation and the apoptosis, which was neutralized by CaMKIIγ overexpression. Finally, miR-219 inhibition reversed the effects of GAS5 silence on epileptic cells, which was eliminated by CaMKIIγ inhibition. In conclusion, GAS5 affected inflammatory response and cell apoptosis of epilepsy via inhibiting miR-219 and further regulating CaMKIIγ/NMDAR pathway (See graphic summary in Supplementary Material).","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"36 1","pages":"32 - 42"},"PeriodicalIF":1.9,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45916724","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":"Novel insights into the genetic profile of hereditary spastic paraplegia in India","authors":"Sundarapandian Narendiran, M. Debnath, S. Shivaram, Ramakrishnan Kannan, Shivani Sharma, R. Christopher, D. Seshagiri, S. Jain, M. Purushottam, Sandhya Mangalore, R. Bharath, P. Bindu, S. Sinha, A. Taly, M. Nagappa","doi":"10.1080/01677063.2022.2064463","DOIUrl":"https://doi.org/10.1080/01677063.2022.2064463","url":null,"abstract":"Abstract The Hereditary Spastic Paraplegias (HSPs) are a group of clinically and genetically heterogeneous disorders characterized by length dependent degeneration of the corticospinal tracts. Genetic data related to HSPs are limited from India. We aimed to comprehensively analyse the phenotypic characteristics and genetic basis of a large cohort of HSP from India. Patients with HSP phenotype were evaluated for their clinical features, electrophysiological and radiological abnormalities. Genetic analyses were carried out by clinical exome sequencing (n = 52) and targeted sequencing (n = 5). The cohort comprised of 57 probands (M:F 40:17, age: 3.5–49 years). Based on the phenotype, the cohort could be categorized as ‘pure’ (n = 15, 26.3%) and ‘complicated’ (n = 42, 73.7%) HSP. Brain MRI showed thin corpus callosum (n = 10), periventricular hyperintensities (n = 20), cerebral atrophy (n = 3), cerebellar atrophy (n = 3) and diffuse atrophy (n = 4). Sixty-seven variants representing 40 genes were identified including 47 novel variants. Forty-eight patients (84.2%) had variants in genes previously implicated in HSP and other spastic paraplegia syndromes (SPG genes = 24, non-SPG genes = 24); among these 13 had variations in more than one gene and 12 patients (21.0%) had variations in genes implicated in potentially treatable/modifiable metabolic disorders (MTHFR = 8, MTRR = 1, ARG1 = 2 and ABCD1 = 1). In nine patients, no genetic variants implicated in spastic paraplegia phenotype were identified. Thus, the present study from India highlights the phenotypic complexities and spectrum of genetic variations in patients with HSP including those implicated in metabolically modifiable disorders. It sets a platform for carrying out functional studies to validate the causal role of the novel variants and variants of uncertain significance.","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"36 1","pages":"21 - 31"},"PeriodicalIF":1.9,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43417024","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":"Fly seizure EEG: field potential activity in the <i>Drosophila</i> brain.","authors":"Atulya Iyengar,&nbsp;Chun-Fang Wu","doi":"10.1080/01677063.2021.1950714","DOIUrl":"https://doi.org/10.1080/01677063.2021.1950714","url":null,"abstract":"<p><p>Hypersynchronous neural activity is a characteristic feature of seizures. Although many <i>Drosophila</i> mutants of epilepsy-related genes display clear behavioral spasms and motor unit hyperexcitability, field potential measurements of aberrant hypersynchronous activity across brain regions during seizures have yet to be described. Here, we report a straightforward method to observe local field potentials (LFPs) from the <i>Drosophila</i> brain to monitor ensemble neural activity during seizures in behaving tethered flies. High frequency stimulation across the brain reliably triggers a stereotypic sequence of electroconvulsive seizure (ECS) spike discharges readily detectable in the dorsal longitudinal muscle (DLM) and coupled with behavioral spasms. During seizure episodes, the LFP signal displayed characteristic large-amplitude oscillations with a stereotypic temporal correlation to DLM flight muscle spiking. ECS-related LFP events were clearly distinct from rest- and flight-associated LFP patterns. We further characterized the LFP activity during different types of seizures originating from genetic and pharmacological manipulations. In the 'bang-sensitive' sodium channel mutant <i>bangsenseless</i> (<i>bss</i>), the LFP pattern was prolonged, and the temporal correlation between LFP oscillations and DLM discharges was altered. Following administration of the pro-convulsant GABA_A blocker picrotoxin, we uncovered a qualitatively different LFP activity pattern, which consisted of a slow (1-Hz), repetitive, waveform, closely coupled with DLM bursting and behavioral spasms. Our approach to record brain LFPs presents an initial framework for electrophysiological analysis of the complex brain-wide activity patterns in the large collection of <i>Drosophila</i> excitability mutants.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"35 3","pages":"295-305"},"PeriodicalIF":1.9,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01677063.2021.1950714","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9113709","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}