Astrocytes control recent and remote memory strength by affecting the recruitment of the CA1→ACC projection to engrams

Cell Reports, Год журнала: 2024, Номер 43(3), С. 113943 - 113943

Опубликована: Март 1, 2024

The maturation of engrams from recent to remote time points involves the recruitment CA1 neurons projecting anterior cingulate cortex (CA1→ACC). Modifications G-protein-coupled receptor pathways in astrocytes affect and recall seemingly contradictory ways. To address this inconsistency, we manipulated these during memory acquisition tagged c-Fos-positive engram cells CA1→ACC recall. behavioral results were coupled with changes projection engram: Gq pathway activation caused enhancement alone was accompanied by earlier engram. In contrast, Gi resulted impairment only recall, not recruited memory. Finally, provide a simple working model, hypothesizing that differently, modulating same mechanism: projection.

Язык: Английский

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Effects of chemogenetic virus injection and clozapine administration in spinal cord injury

Neurotherapeutics, Год журнала: 2025, Номер unknown, С. e00547 - e00547

Опубликована: Фев. 1, 2025

Neuromodulation therapy using chemogenetic stimulation has shown potential in enhancing motor recovery and neuroregeneration following spinal cord injury (SCI). These therapeutic benefits are hypothesized to result from the promotion of neuroplasticity, particularly when administered during acute phase injury. In this study, we investigated effects Designer Receptors Exclusively Activated by Drugs (DREADDs) conjunction with clozapine, a ligand for receptor activation. DREADDs enable targeted, reversible neuromodulation, facilitating histological characterization engineered neurons. We utilized these receptors modulate G-protein-coupled (GPCR) signaling pathways, leading activation or inhibition intracellular signaling. The objective was determine whether administration clozapine (0.1 ​mg/kg) could enhance function neuronal recovery, applied SCI. Weekly behavioral assessments demonstrated significant improvements skills regeneration treated animals compared controls, most pronounced observed initiated early after enhancements neuroplasticity were reflected improved ladder rung test scores Basso, Beattie, Bresnahan (BBB) scale results DREADDs-treated rats. Histological analyses, including immunohistochemistry (IHC) staining, Western blotting, quantitative reverse transcription PCR (qRT-PCR), confirmed that treatment group exhibited higher density neurons, increased protein expression, reduced inflammatory markers. findings suggest stimulation, phase, effectively promotes recovery. Future research should focus on assessing long-term safety efficacy virus injection administration, an emphasis timing intervention.

Язык: Английский

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Activation of the hippocampal CA1 astrocyte Gq and Gi G protein-coupled receptors exerts a protective effect against attention deficit hyperactivity disorder

International Immunopharmacology, Год журнала: 2025, Номер 152, С. 114382 - 114382

Опубликована: Март 5, 2025

Язык: Английский

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Astrocytes in Rodent Anxiety-Related Behavior: Role of Calcium and Beyond

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(6), С. 2774 - 2774

Опубликована: Март 19, 2025

Anxiety is a physiological, emotional response that anticipates distal threats. When kept under control, anxiety beneficial response, helping animals to maintain heightened attention in environments with potential dangers. However, an overestimation of threats can lead excessive expression that, humans, may evolve into disorders. Pharmacological treatments show variable efficacy among patients, highlighting the need for more efforts better understand pathogenesis Mounting evidence suggests astrocytes, type glial cells, are active partners neurons brain circuits and regulation behaviors both physiological pathological conditions. In this review, I summarize current literature on role astrocytes from different regions modulating anxious states, goal exploring novel cerebral mechanisms identify innovative therapeutic targets treatment

Язык: Английский

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Somatostatin neurons detect stimulus-reward contingencies to reduce neocortical inhibition during learning

Cell Reports, Год журнала: 2025, Номер 44(5), С. 115606 - 115606

Опубликована: Апрель 20, 2025

Язык: Английский

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Neuronal activation of Gαq EGL-30/GNAQ late in life rejuvenates cognition across species

Cell Reports, Год журнала: 2023, Номер 42(9), С. 113151 - 113151

Опубликована: Сен. 1, 2023

Loss of cognitive function with age is devastating. EGL-30/GNAQ and Gαq signaling pathways are highly conserved between C. elegans mammals, murine Gnaq enriched in hippocampal neurons declines age. We found that activation EGL-30 aged worms triples memory span, GNAQ gain significantly improved mice: GNAQ(gf) 24-month-old mice (equivalent to 70- 80-year-old humans) rescued age-related impairments well-being memory. Single-nucleus RNA sequencing revealed increased expression genes regulating synaptic function, axon guidance, GNAQ-treated mice, worm orthologs these were required for long-term extension worms. These experiments demonstrate a powerful model identify mammalian regulators memory, leading the identification pathway improves extremely old mice. To our knowledge, this oldest at which an intervention has decline.

Язык: Английский

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Astrocytes in the Ventral Hippocampus Bidirectionally Regulate Innate and Stress‐Induced Anxiety‐Like Behaviors in Male Mice

Advanced Science, Год журнала: 2024, Номер 11(38)

Опубликована: Авг. 9, 2024

Abstract The mechanisms of anxiety disorders, the most common mental illness, remain incompletely characterized. ventral hippocampus (vHPC) is critical for expression anxiety. However, current studies primarily focus on vHPC neurons, leaving role astrocytes in largely unexplored. Here, genetically encoded Ca 2+ indicator GCaMP6m and vivo fiber photometry calcium imaging are used to label monitor their activity, respectively, genetic chemogenetic approaches inhibit activate astrocytes, patch‐clamp recordings measure glutamate currents, behavioral assays assess anxiety‐like behaviors. It found that astrocytic activity increased anxiogenic environments by 3‐d subacute restraint stress (SRS), a well‐validated mouse model disorders. Genetic inhibition exerts anxiolytic effects both innate SRS‐induced anxiety‐related behaviors, whereas hM3Dq‐mediated or activation enhances which reversed intra‐vHPC application ionotropic N‐methyl‐ d ‐aspartate receptor antagonists. Furthermore, systemic antagonist memantine, U.S. FDA‐approved drug Alzheimer's disease, fully rescues findings highlight as regulators potential therapeutic targets

Язык: Английский

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Chronic activation of a negative engram induces behavioral and cellular abnormalities

eLife, Год журнала: 2024, Номер 13

Опубликована: Апрель 17, 2024

Negative memories engage a brain and body-wide stress response in humans that can alter cognition behavior. Prolonged responses induce maladaptive cellular, circuit, systems-level changes lead to pathological states corresponding disorders which mood memory are affected. However, it is unclear if repeated activation of cells processing negative induces similar phenotypes mice. In this study, we used an activity-dependent tagging method access neuronal ensembles assess their molecular characteristics. Sequencing engrams mice revealed positive (male-to-female exposure) (foot shock) upregulated genes linked anti- pro-inflammatory responses, respectively. To investigate the impact persistent engrams, chemogenetically activated them ventral hippocampus over 3 months conducted anxiety memory-related tests. engram increased behaviors both 6- 14-month-old mice, reduced spatial working older impaired fear extinction younger heightened generalization age groups. Immunohistochemistry microglial astrocytic structure number hippocampus. summary, lasting cellular behavioral abnormalities offering insights into effects chronic thinking-like on human health.

Язык: Английский

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Activation of the hippocampal CA1 astrocyte Gq and Gi G protein-coupled receptors exerts a protective effect against attention deficit hyperactivity disorder

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Фев. 9, 2024

Abstract Background Attention deficit hyperactivity disorder (ADHD) is characterized by symptoms such as inattention, and impulsiveness, which significantly impact the healthy development of children. Our prior research demonstrated that exposure to S-Ketamine during pregnancy can lead ADHD, existing studies have established a close association between astrocytes onset progression ADHD. The activation inhibition are closely linked neuropsychiatric dysfunction, astrocytic NOD-like receptor protein 3 (NLRP3) has been reported contribute alterations in mental state cognitive deficits. Thus, this study aims investigate role ADHD selectively modulating astrocyte function through Gq Gi G protein-coupled receptors (GPCRs) specifically targeting knockout NLRP3. Methods Pregnant C57BL/6J mice or with specific deletion NLRP3 were administered intraperitoneal injections 15 mg/kg S-ketamine for 5 consecutive days from gestational day 14 18 establish an model. To modulate activity hippocampal CA1 region, we astrocyte-specific Gq-Adeno-associated virus (AAV) Gi-AAV into maintained treatment CNO. At 21 postnatally, conducted open field test (OFT), novel object recognition (NOR), elevated plus maze (EPM) fear conditioning (FC) offspring mice. Additionally, on postnatal 14, implanted electrodes region neurophysiological monitoring investigated local potentials (LFP) exploration 21. Lastly, pathological assessments after euthanasia. Results Both improved impulsive-like behaviors mice, reduced power theta (θ) oscillations decreased NLRP3-associated inflammatory factors, including cleaved caspase-1 IL-8. Furthermore, compared WT conditional impulsive behavior deficits, well decrease θ oscillation reduction factors. Conclusions data provide compelling evidence pathways improves ADHD-like NLRP3-dependent mechanisms.

Язык: Английский

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Chronic activation of a negative engram induces behavioral and cellular abnormalities

Опубликована: Апрель 17, 2024

Negative memories engage a brain and body-wide stress response in humans that can alter cognition behavior. Prolonged responses induce maladaptive cellular, circuit, systems-level changes lead to pathological states corresponding disorders which mood memory are affected. However, it’s unclear if repeated activation of cells processing negative induces similar phenotypes mice. In this study, we used an activity-dependent tagging method access neuronal ensembles assess their molecular characteristics. Sequencing engrams mice revealed positive (male-to-female exposure) (foot shock) upregulated genes linked anti- pro-inflammatory responses, respectively. To investigate the impact persistent engrams, chemogenetically activated them ventral hippocampus over three months conducted anxiety memory-related tests. engram increased behaviors both 6- 14-month-old mice, reduced spatial working older impaired fear extinction younger heightened generalization age groups. Immunohistochemistry microglia astrocytes, alongside GABAergic fluorescence reduction hippocampus. summary, lasting cellular behavioral abnormalities offering insights into effects rumination on human health.

Язык: Английский

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