Expression profiles and functional prediction of ionotropic receptors in Asian corn borer, Ostrinia furnacalis(Lepidoptera:Crambidae)

Genes involved in chemosensation are essential for odorant-mediated insect behaviors. Odorant receptors(ORs) bind and respond to pheromones and plant volatiles, regulating insect behaviors such as mating and host-plant selection, while ionotropic receptors(IRs), which are present at lower levels in insects than ORs, influence ion channels, especially in agricultural pests. Asian corn borer, Ostrinia furnacalis, is the main pest of maize that causes huge economic losses in Asia. Twenty-one Ofur IRs have been identified, but none has been characterized. In this study, tissue-specific expression profiling, phylogenetic analysis, and electroantennography(EAG) analysis were applied to characterize the evolution, expression, and the potential function of Ofur IRs. It was found that 20 Ofur IRs were highly expressed in the antennae, except for Ofur IR75p3, whereas 10 and nine Ofur IRs were highly expressed in the proboscis and genitalia, respectively, indicating that these Ofur IRs were functionally associated with feeding and oviposition. EAG results showed that seven acids elicited responses in the antennae of O. furnacalis and that 2-oxopentanoic acid displayed a significant femalebiased response. Combined with the phylogenetic analysis, 10 Ofur IRs in clade 4 were roughly predicted to be candidate receptors for 2-oxopentanoic acid and other tested acids. These results provide basic information about Ofur IRs and may help advance the knolwedge on the olfactory system of O. furnacalis.

Ionotropic receptors mediate olfactory learning and memory in Drosophila

Phenylacetaldehyde(PAH),an aromatic compound,is present in a diverse range of fruits including overripe bananas and prickly pear cactus,the two major host fruits for Drosophila melanogaster.PAH acts as a potent ligand for the ionotropic receptor 84a(IR84a)in the adult fruit fly and it is detected by the IR84a/IR8a heterotetrameric complex.Its role in the male courtship behavior through IR84a as an environmental aphrodisiac is of additional importance.In D.melanogaster,two distinct kinds of olfactory receptors,that is,odorant receptors(ORs)and ionotropic receptors(IRs),perceive the odorant stimuli.They display unique structural,molecular,and functional characteristics in addition to having different evolutionary origins.Traditionally,olfactory cues detected by the ORs such as ethyl acetate,1-butanol,isoamyl acetate,1-octanol,4-methylcyclohexanol,etc.classified as aliphatic esters and alcohols have been employed in olfactory classical conditioning using fruit flies.This underlines the participation of OR-activated olfactory pathways in learning and memory formation.Our study elucidates that likewise ethyl acetate(EA)(an OR-responsive odorant),PAH(an IR-responsive aromatic compound)too can form learning and memory when associated with an appetitive gustatory reinforcer.The association of PAH with sucrose(PAH/SUC)led to learning and formation of the long-term memory(LTM).Additionally,the Orco^(1),Ir84a^(MI00501),and Ir8a^(1)mutant flies were used to confirm the exclusive participation of the IR84a/IR8a complex in PAH/SUC olfactory associative conditioning.These results highlight the involvement of IRs via an IR-activated pathway in facilitating robust olfactory behavior.

Mechanism of charged interface of stargazin EX1 on AMPAR opening and desensitization

OBJECTIVE AMPA-subtype iono⁃tropic glutamate receptors(iGluRs)mediate fast excitatory synaptic transmission in the mammali⁃an central nervous system(CNS).It plays the key role in many central nerves disorder such as epilepsy,depression and schizophrenia.Star⁃gazin(STZ,also named TARP-γ2),as the first TARPs found in CNS,potentiates AMPAR activity by attenuating deactivation and desensitization,enhancing recovery from desensitization,and facilitating agonist affinity and efficacy.However,it is still not fully understanding howγ-2 modu⁃late AMPAR gating.METHODS AND RESULTS The desensitization for different mutation of AMPAR andγ-2 was compared.It was shown that the electric attraction was involved in the interaction of AMPAR andγ-2.In addition,the interaction of KGK motif in ligand binding domain and pre-M1 chain of AMPAR and EX1 ofγ-2 modulate AMPAR opening and desensitization.Substitution of these charged residues had sur⁃prisingly effects on AMPAR desensitization kinet⁃ics.CONCLUSION The electric attraction has two impacts on the channels gating process the first destablizing the receptor closed state and enabling the channel opening,the second pro⁃moting the channels entering desensitization state upon the channel opening.

Mechanisms of glutamate metabolic function and dysfunction in vasculardementia

As the global population ages,research on the pathogenesis and treatment options for older patients with dementia has become increasingly important.Vascular dementia(VaD),the second most frequent type of dementia,is characterized by vascular impairment caused by inadequate blood supply to the brain.VaD is a complex neurological disorder involving multiple cells and signaling pathways,and its prevention and treatment pose clinical challenges with significant behavioral implications.Glutamate,the most abundant amino acid in the brain,plays a critical role as an excitatory neurotransmitter,impacting cognitive function,learning,and memory.Abnormal glutamate metabolism has been closely linked to dementia,and reduced blood flow to the brain can lead to excessive glutamate accumulation,resulting in neuronal death.This article highlights the connection between VaD and glutamate metabolism,aiming to identify better methods for preventing and treating VaD via regulating glutamate metabolism.

Ionotropic receptor 8a is involved in the attraction of Helicoverpa armigera to acetic acid

Ionotropic receptors(IRs)were first found in Drosophila melanogaster,and derive from ionotropic glutamate receptors(iGluRs),which are implicated in detecting acids,ammonia,amine,temperature and humidity.Although IRs are involved in sensing acid odors in a few insects,such as D.melanogaster,Aedes aegypti,and Manduca sexta,the function of IRs in Helicoverpa armigera is still unknown.IR8a was confirmed to be a co-receptor associated with acid detection.From the results of phylogenetic analysis,HarmIR8a displayed high similarity compared to homologs in D.melanogaster,M.sexta,and A.aegypti,suggesting that HarmIR8a might have a consistent function as a co-receptor for acid detection.In this study,clustered regularly interspaced palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)-mediated genome editing was implemented to knockout HarmIR8a for in vivo functional analysis.Electrophysiological and behavioral assays were performed to compare the differences between HarmIR8a knockout mutants and wild type individuals.From electroantennogram(EAG)analysis,we found that wild type H.armigera adults could detect short-chain carboxylic acids.In addition,wind tunnel experiments showed that 1%acetic acid attracted wild type H.armigera adults.However,acid sensing and attraction were reduced or abolished in the HarmIR8a knockout mutants.Our data suggest that HarmIR8a is important for H.armigera to detect short-chain carboxylic acids and mediate attraction behavior to acetic acid.

Glutamate and excitotoxicity in central nervous system disorders:ionotropic glutamate receptors as a target for neuroprotection

Recent advances in neuroscience have illuminated the central role of glutamate dysregulation in various neurological disorders.The glutamatergic system has emerged as a central player in the pathophysiology of various neurological disorders.The dysregulation of glutamate signaling,leading to excitotoxicity and neuronal cell death,has been a focal point in understanding the underlying mechanisms of these conditions.This has prompted a paradigm shift in neuroprotection research,with a growing emphasis on targeting ionotropic glutamate receptors(iGluRs)to restore glutamatergic homeostasis.This review provides a comprehensive overview of recent advancements in the field of iGluR-targeted neuroprotection.We further investigate the implications of glutamate dysregulation in the central nervous system(CNS)disorders,highlighting the complex interplay between excitotoxicity and neuroprotection.We elucidate the multifaceted factors that render neurons vulnerable to excitotoxic damage,emphasizing the need for innovative therapeutic approaches.This review provides an extensive survey of the burgeoning field of iGluR-targeted neuroprotection.It showcases the significant potential of a wide array of compounds,encompassing both natural and synthetic agents,to modulate iGluRs and ameliorate excitotoxicity and oxidative stress-induced neuronal damage.These compounds have demonstrated impressive neuroprotective effects in diverse experimental models,from glutamate-induced toxicity to traumatic brain injuries.We advocate for further research and clinical investigations to harness the full therapeutic potential of iGluR modulation,heralding a promising era in neuroprotection and CNs disorder management.

Connexin 36 Mediates Orofacial Pain Hypersensitivity Through GluK2 and TRPA1

Trigeminal neuralgia is a debilitating condition,and the pain easily spreads to other parts of the face.Here,we established a mouse model of partial transection of the infraorbital nerve(pT-ION)and found that the Connexin 36(Cx36)inhibitor mefloquine caused greater alleviation of pT-ION-induced cold allodynia compared to the reduction of mechanical allodynia.Mefloquine reversed the pT-IONinduced upregulation of Cx36,glutamate receptor ionotropic kainate 2(GluK2),transient receptor potential ankyrin 1(TRPA1),and phosphorylated extracellular signal regulated kinase(p-ERK)in the trigeminal ganglion.Cold allodynia but not mechanic al allodynia induced by pT-ION or by virusmediated overexpression of Cx36 in the trigeminal ganglion was reversed by the GluK2 antagonist NS 102,and knocking down Cx36 expression in Nav1.8-expressing nociceptors by injecting virus into the orofacial skin area of Nav1.8-Cre mice attenuated cold allodynia but not mechanic al allodynia.In conclusion,we show that Cx36 contributes greatly to the development of orofacial pain hypersensitivity through GluK2,TRPA1,and p-ERK signaling.