Search

Impaired extinction of fear memory is one of the most common symptoms in post‐traumatic stress disorder (PTSD), with limited therapeutic strategies due to the poor understanding of its underlying neural substrates. In this study, functional screening is performed and identified hyperactivity in the mediodorsal thalamic nucleus (MD) during fear extinction. Furthermore, the encoding patterns of the hyperactivated MD is investigated during persistent fear responses using multiple machine learning algorithms. The anterior cingulate cortex (ACC) is also identified as a functional downstream region of the MD that mediates the extinction of fear memory. The thalamocortical circuit is comprehensively analyzed and found that the MD‐ACC parvalbumin interneurons circuit is preferentially enhanced in PTSD mice, disrupting the local excitatory and inhibitory balance. It is found that decreased phosphorylation of the Kv3.2 channel contributed to the hyperactivated MD, primarily to the malfunctioning thalamocortical circuit. Using a lipid nanoparticle‐based RNA therapy strategy, channelopathy is corrected via a methoxylated siRNA targeting the protein phosphatase 6 catalytic subunit and restored fear memory extinction in PTSD mice. These findings highlight the function of the thalamocortical circuit in PTSD‐related impaired extinction of fear memory and provide therapeutic insights into Kv3.2‐targeted RNA therapy for PTSD. [ABSTRACT FROM AUTHOR]

Paradoxical sleep deprivation (PSD) is prevalent in modern society, and impaired memory is one of its serious consequences. The pathogenic mechanism is still unclear, and the therapeutic strategies for PSD are limited. Here, we found that quercetin treatment ameliorated memory impairments caused by PSD in a dose-dependent manner in an animal model. Quercetin could restore the dynamic changes of the gamma band while the animals performed novel object recognition (NOR) tasks as determined by electroencephalogram analysis. Morphological analysis showed that quercetin, by targeting the hippocampal CA1 region, strikingly ameliorated the overactivation of microglia induced by PSD. Mechanistically, quercetin inhibited the toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor kappa-b (NF-κB) cascade, which is critical for abnormal microglial activation following PSD stress. Our results provided experimental evidence for the therapeutic effects of quercetin on PSD-related memory impairments by suppressing TLR4/MyD88/NF-κB signaling that mediated abnormal microglia activation in the hippocampus. [Display omitted] • Quercetin ameliorated memory impairment induced by PSD stress in a dose-dependent manner. • Quercetin restored the dynamics of the gamma band in PSD mice while the mice performed novel object recognition. • Quercetin significantly alleviated microglia activation caused by PSD. • Quercetin inhibited the abnormal activation of microglia by suppressing the TLR4/MyD88/NF-κB pathway. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by social disorder and stereotypical behaviors with an increasing incidence. ASD patients are suffering from varying degrees of mental retardation and language development abnormalities. Magnetic resonance imaging (MRI) is a noninvasive imaging technology to detect brain structural and functional dysfunction in vivo, playing an important role in the early diagnosisbasic research of ASD. High‐field, small‐animal MRI in basic research of autism model mice has provided a new approach to research the pathogenesis, characteristics, and intervention efficacy in autism. This article reviews MRI studies of mouse models of autism over the past 20 years. Reduced gray matter, abnormal connections of brain networks, and abnormal development of white matter fibers have been demonstrated in these studies, which are present in different proportions in the various mouse models. This provides a more macroscopic view for subsequent research on autism model mice. This article is categorized under:Cognitive Biology > Genes and EnvironmentNeuroscience > ComputationNeuroscience > Genes, Molecules, and CellsNeuroscience > Development [ABSTRACT FROM AUTHOR]

Background and Purpose: Quercetin is a well‐known plant flavonoid with neuroprotective properties. Earlier work suggested it may relieve psychiatric disorders, cognition deficits and memory dysfunction through anti‐oxidant and/or radical scavenging mechanisms. In addition, quercetin modulated the physiological function of some ion channels. However, the detailed ionic mechanisms of the bioeffects of quercetin remain unknown. Experimental Approach Effects of quercetin on neuronal activities in the prefrontal cortex (PFC) and its ionic mechanisms were analysed by calcium imaging using mice bearing a green fluorescent protein, calmodulin, and M13 fusion protein and patch clamp in acute brain slices from C57BL/6 J mice and in HEK 293 cells. The possible ionic mechanism of action of quercetin on D‐amphetamine‐induced manic‐like effects in mice was explored with c‐fos staining and the open field behaviour test. Key Results: Quercetin reduced calcium influx triggered by PFC pyramidal neuronal activity. This effect involved increasing the rheobase of neuronal firing through decreasing membrane resistance following quercetin treatment. Spadin, a blocker of TREK‐1 potassium channels, also blocked the effect of quercetin on the membrane resistance and neuronal firing. Further, spadin blocked the neuroprotective effects of quercetin. The effects of quercetin on TREK‐1 channels could be mimicked by GF109203X, a protein kinase C inhibitor. In vivo, injection of quercetin relieved the manic hyperlocomotion in mice, induced by D‐amphetamine. This action was partly alleviated by spadin. Conclusion and Implications: TREK‐1 channels are a novel target for quercetin, by inhibiting PKC. This action could contribute to both the neuroprotective and anti‐manic‐like effects. [ABSTRACT FROM AUTHOR]

The cover image is based on the Advanced Review Progress in magnetic resonance imaging of autism model mice brain by Dingding Yang et al., https://doi.org/10.1002/wcs.1616. [ABSTRACT FROM AUTHOR]

Autism spectrum disorders (ASDs) comprise a range of disorders that share a core of neurobehavioural deficits characterized by widespread abnormalities in social interactions, deficits in communication as well as restricted interests and repetitive behaviours. The neurological basis and circuitry mechanisms underlying these abnormal behaviours are poorly understood. SHANK3 is a postsynaptic protein, whose disruption at the genetic level is thought to be responsible for the development of 22q13 deletion syndrome (Phelan-McDermid syndrome) and other non-syndromic ASDs. Here we show that mice with Shank3 gene deletions exhibit self-injurious repetitive grooming and deficits in social interaction. Cellular, electrophysiological and biochemical analyses uncovered defects at striatal synapses and cortico-striatal circuits in Shank3 mutant mice. Our findings demonstrate a critical role for SHANK3 in the normal development of neuronal connectivity and establish causality between a disruption in the Shank3 gene and the genesis of autistic-like behaviours in mice. [ABSTRACT FROM AUTHOR]