Lactobacillus reuteri normalizes altered fear memory in CNTNAP4 knockout mouse
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ABSTRACT:
ORGANISM(S): Mus
PROVIDER: GSE208397 | GEO | 2022/07/21
REPOSITORIES: GEO
Similar Datasets
Project description:To explore function that CNTNAP4 in the regulation of GABAergic transmission,, we profiled basolateral amygdala from wild-type and CNTNAP4 knockout in male mice by RNA sequencing (RNA-seq).
2022-07-22 | GSE208542 | GEO
Project description:Lactobacillus reuteri normalizes altered fear memory in CNTNAP4 knockout mouse
| PRJNA859798 | ENA
Project description:BackgroundAutism spectrum disorder (ASD) is a common neurodevelopmental disease, characterized by deficits in social communication, restricted and repetitive behaviours, and impaired fear memory processing. Severe gastrointestinal dysfunction and altered gut microbiome have been reported in ASD patients and animal models. Contactin associated protein-like 4 (CNTNAP4) has been suggested to be a novel risk gene, though its role in ASD remains unelucidated.MethodsCntnap4-/- mice were generated to explore its role in ASD-related behavioural abnormalities. Electrophysiological recording was employed to examine GABAergic transmission in the basolateral amygdala (BLA) and prefrontal cortex. RNA-sequencing was performed to assess underlying mechanisms. 16S rDNA analysis was performed to explore changes in faecal microbial composition. Male Cntnap4-/- mice were fed with Lactobacillus reuteri (L. reuteri) or faecal microbiota to evaluate the effects of microbiota supplementation on the impaired fear conditioning mediated by Cntnap4 deficiency.FindingsMale Cntnap4-/- mice manifested deficiency in social behaviours and tone-cue fear conditioning. Notably, reduced GABAergic transmission and GABA receptor expression were found in the BLA but not the prefrontal cortex. In addition, gut Lactobacillus were less abundant in male Cntnap4-/- mice, and L. reuteri treatment or faecal microbiota transplantation rescued abnormal tone-cued fear memory and improved local GABAergic transmission in the BLA of male Cntnap4-/- mice.InterpretationCntnap4 shapes GABAergic transmission of amygdala and fear conditioning, and microbial intervention represents a promising therapy in ASD intervention.FundingNational Natural Science Foundation of China, Science and Technology Planning Project of Guangzhou, Guangzhou Medical University, and China Postdoctoral Science Foundation.
| S-EPMC9672961 | biostudies-literature
Project description:Lactobacillus reuteri normalizes altered fear memory in CNTNAP4 knockout mouse (male)
| PRJNA860079 | ENA
Project description:The amygdala or amygdala-like structure in the brain are found in all vertebrates, and plays a critical role for emotional processing. But the cellular architecture of amygdala and how they evolved are still elusive. Here, we generated single-nucleus RNA-sequencing data for more than 200,000 cells in human, macaque, mouse and chicken amygdala. Abundant neuronal cell types derived from different subnuclei of amygdala were identified in all datasets. Cross-species analyses revealed GABAergic neurons and GABAergic neuron-enriched subnuclei of amygdala were well-conserved in cellular composition and marker gene expression, whereas glutamatergic neuron-enriched subnuclei were relatively divergent. Furthermore, we discovered that LAMP5+ interneurons were much more numerous in primates, while DRD2+ GABAergic neurons, LAMP5+ and SATB2+ glutamatergic neurons were predominant in the human central amygdalar nucleus (CEA) and basolateral amygdala complex (BLA), respectively. In addition, we also identified GABAergic neuron-enriched subnuclei of amygdala in the chicken. Altogether, our study highlight extremely cell-type diversity in the amygdala across species and their species-specifc adaptations.
2022-12-13 | GSE195445 | GEO
Project description:Memory encodes past experiences, thereby enabling future plans. The basolateral amygdala (BLA) is a center of salience networks that underlie emotional experiences and thus plays a key role in long-term fear memory formation. Here we used single-cell transcriptomics to illuminate the cellular and molecular architecture of the role of the basolateral amygdala in long-term memory. We identified transcriptional signatures in subpopulations of neurons and astrocytes that were memory-specific and persisted for weeks. These transcriptional signatures implicate neuropeptide and brain-derived neurotrophic factor (BDNF) signaling, mitogen-activated protein kinase (MAPK) and cAMP response element-binding protein (CREB) activation, ubiquitination pathways, and synaptic connectivity as key components of long-term memory. Strikingly, upon long-term memory formation a neuronal sub-population defined by increased Penk and decreased Tac expression constituted the most prominent component of the BLA’s memory engram.
2023-10-26 | GSE246147 | GEO
Project description:Fear conditioning in rats leads to long term memory (LTM) formation. A central neural substrate for LTM is the basolateral amygdala. We sought the expression changes specific to LTM at 6h following anesthesia with isoflurane (a general anesthetic and an effective amnestic agent), following pain (a component of conditioning), and following conditioning in presence and absence of isoflurane.
2007-06-29 | E-GEOD-1779 | biostudies-arrayexpress
Project description:Fear extinction is an adaptive behavioral process critical for organism’s survival, but deficiency in extinction may lead to PTSD. While the amygdala and its neural circuits are critical for fear extinction, the molecular identity and organizational logic of cell types that lie at the core of these circuits remain unclear. Here we report that mice deficient for amygdala-enriched gastrin-releasing peptide gene (Grp-/-) exhibit enhanced neuronal activity in the basolateral amygdala (BLA) and stronger fear conditioning, as well as deficient extinction in stress-enhanced fear learning (SEFL). rAAV2-retro-based tracing combined with visualization of the GFP knocked in the Grp gene showed that BLA receives several GRPergic conditioned stimulus projections: from the indirect auditory thalamus-to-auditory cortex pathway, medial prefrontal cortex, ventral hippocampus and ventral tegmental area. Transcription of dopamine-related genes was decreased in BLA of Grp-/- mice following SEFL extinction recall, suggesting that the GRP may mediate fear extinction regulation by dopamine.
2021-12-01 | GSE164226 | GEO
Project description:Here we tested a hypothesis that epileptogenesis influences expression pattern of genes in the basolateral amygdala that are critical for fear conditioning. Whole genome molecular profiling of basolateral rat amygdala was performed to compare the transcriptome changes underlying fear learning in epileptogenic and control animals. Our analysis revealed that after acquisition of fear conditioning 26 genes were regulated differently in the basolateral amygdala of both groups. Thus, our study provides the first evidence that not only the damage to the neuronal pathways but also altered composition or activity level of molecular machinery responsible for formation of emotional memories within surviving pathways can contribute to impairment in emotional learning in epileptogenic animals. Understanding the function of those genes in emotional learning provides an attractive avenue for identification of novel drug targets for treatment of emotional disorders after epileptogenesis-inducing insult. Experiment Overall Design: Experiment description: Experiment Overall Design: Array: Rat Genome 230-2.0 (Affymetrix). Experiment Overall Design: Samples: 2 biological replicates from 4 experimental groups (control unpaired = CU, CU1, control paired = CP, CP1, epileptogenic unpaired = EU, EU1, epileptogenic paired = EP, EP1). Experiment Overall Design: Animals&model: Amygdala stimulation model (Nissinen et al., 2000): Experiment Overall Design: control (C) animals = operated, not stimulated; Experiment Overall Design: epileptogenic (E) animals = stimulated, responded with "good" status epilepticus (at least 40HAFDs within first 3h of SE), not expressing spontaneous seizures through the whole study. Experiment Overall Design: All animals received 5 habituation session to the fear conditioning apparatus lasting 10 min, starting on day 5 (2 sessions on day 5 and 6 and 1 session on day 7) after stimulation (induction of SE). Experiment Overall Design: On 8th day after stimulation: Experiment Overall Design: unpaired (U) = twice received: 2min in apparatus â footshock (1.5mA, 1s)â tone (75dB for 20 sec) Experiment Overall Design: paired (P) = twice received: 2min in apparatus â tone (75dB for 20 sec) co-terminated by footshock (1.5mA, 1s). Experiment Overall Design: RNA isolation: decapitation â ipsilateral temporal lobe isolated, embed in OCT and frozen in -70C. Cut into 10µm sections, thionin stained (Ambion protocol), basal and lateral nuclei of the amygdala laser-microdissected; total cellular RNA isolated with PicoPure RNA isolation kit (Arcturus). Experiment Overall Design: RNA amplification: 30ng of of total cellular RNA from each rat underwent of 2 rounds of amplification using MessageAmp II aRNA kit (Ambion), according to manufacturer protocol (in vitro transcription time 14h in both rounds). Experiment Overall Design: Sample pooling: aRNA from 2 animals was pooled (10µg in total = 2x5µg) and 8 samples were labeled and hybridized: CP, CP1, CU, CU1, EP, EP1, EU, EU1; (altogether aRNA from 16 rats was used).
2009-02-26 | E-GEOD-13624 | biostudies-arrayexpress
Project description:GABAergic transmission controls cortical sleep, however the molecular determinants of GABAergic control of this phenomenon are unknown. We used immunoprecipitation of the inhibitory postsynaptic protein gephyrin to identify gephyrin interactors at ZT6 (sleep) and ZT6 with sleep deprivation (ZT6SD).
2024-07-25 | PXD048929 | Pride