Early social deficits in TgF344-AD rats are accompanied by sex-specific parvalbumin-positive interneuron reduction and altered brain oscillations in the hippocampal CA2

Neurobiology of Disease, Год журнала: 2025, Номер unknown, С. 106875 - 106875

Опубликована: Март 1, 2025

Social withdrawal and deficits in social cognition are hallmarks of Alzheimer's disease (AD). While early behavior memory have been documented mouse AD models, they remain understudied rat models. Early-stage is accompanied by dysfunction parvalbumin-positive (PV+) interneurons, implicating their potential connection to symptoms. In this study, we employed a 5-trial task investigate 6-month-old TgF344-AD male female rats. We counted the number PV+ interneurons recorded local field potentials during interactions hippocampal CA2 - region critical for information processing. Our results show decreased interest novelty preference However, reduced interneuron numbers were observed only rats specific area. The electrophysiological recordings revealed theta-gamma phase-amplitude coupling direct interactions. conclude that accompany early-stage potentially linked brain oscillatory hippocampus.

Язык: Английский

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Upregulated inwardly rectifying K⁺ current-mediated hypoactivity of parvalbumin interneuron underlies autism-like deficits in <i>Bod1</i>-deficient mice

Journal of Biomedical Research, Год журнала: 2025, Номер 39, С. 1 - 1

Опубликована: Янв. 1, 2025

Parvalbumin-positive (PV +) interneuron dysfunction is believed to be linked autism spectrum disorder (ASD), a neurodevelopmental disorder, characterized by social deficits and stereotypical behaviors. However, the underlying mechanisms of PV + remain largely unclear. Here, we found that deficiency biorientation defective 1 ( Bod1) in led an ASD-like phenotype Pvalb-Cre; Bod1 f/f mice. Mechanistically, identified induced hypoactivity hyperactivity calcium/calmodulin-dependent protein kinase Ⅱ alpha (CaMKⅡα) neurons medial prefrontal cortex (mPFC), as determined whole-cell patch-clamp recording. Additionally, it concurrently decreased power high gamma oscillation, assessed vivo multi-channel electrophysiological Furthermore, enhanced inwardly rectifying K current, leading increase resting membrane potential interneurons. Importantly, gain-of-function improved behaviors These findings provide mechanistic insights into suggest new strategies for developing therapies ASD.

Язык: Английский

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A dorsal hippocampus-prodynorphinergic dorsolateral septum-to-lateral hypothalamus circuit mediates contextual gating of feeding

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 6, 2024

SUMMARY Adaptive regulation of feeding depends on linkage internal states and food outcomes with contextual cues. Human brain imaging has identified dysregulation a hippocampal-lateral hypothalamic area (LHA) network in binge eating, but mechanistic instantiation underlying cell-types circuitry is lacking. Here, we identify an evolutionary conserved discrete Prodynorphin ( Pdyn )-expressing subpopulation Somatostatin Sst inhibitory neurons the dorsolateral septum (DLS) that receives primarily dorsal, not ventral, hippocampal inputs. DLS( ) inhibit LHA GABAergic confer context- state-dependent calibration feeding. Viral deletion DLS mimicked effects seen optogenetic silencing INs, suggesting potential role for DYNORPHIN-KAPPA OPIOID RECEPTOR signaling food-seeking. Together, our findings illustrate how dorsal hippocampus evolved to recruit ancient circuit module through link information consumption. HIGHLIGHTS receive dense input from ventral Silencing hippocampus-DLS( )-LHA nodes abolishes context-conditioned necessary

Язык: Английский

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Inhibitory neurons defined by a synaptogenic molecule impair memory discrimination

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 7, 2024

SUMMARY The CA3 region is central to hippocampal function during learning and memory has a unique connectivity. pyramidal neurons are the targets of huge, excitatory mossy fiber synapses from DG axons have high degree recurrent Thus, inhibition likely plays an outsized importance in constraining excitation shaping ensembles memory. Here, we investigate never-before studied set dendrite-targeting, GABAergic defined by expression synaptic adhesion molecule, Kirrel3. We discovered that activating Kirrel3-expressing specifically impairs discrimination inhibits novel contexts. Kirrel3 required for DG-to-GABA synapse formation variants strong risk factors neurodevelopmental disorders. our work suggests Kirrel3-GABA critical source feed-forward encoding retrieval contextual memories, which may be disrupted some brain

Язык: Английский

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An aging-sensitive compensatory secretory phospholipase that confers neuroprotection and cognitive resilience

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 26, 2024

Breakdown of lipid homeostasis is thought to contribute pathological aging, the largest risk factor for neurodegenerative disorders such as Alzheimer's Disease (AD). Cognitive reserve theory posits a role compensatory mechanisms in aging brain preserving neuronal circuit functions, staving off cognitive decline, and mitigating AD. However, identities have remained elusive. A screen hippocampal dentate granule cell (DGC) synapse loss-induced factors identified secreted phospholipase

Язык: Английский

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Repeated postnatal sevoflurane exposure impairs social recognition in mice by disrupting GABAergic neuronal activity and development in hippocampus

British Journal of Anaesthesia, Год журнала: 2024, Номер 133(4), С. 810 - 822

Опубликована: Авг. 13, 2024

Язык: Английский

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An aging-sensitive compensatory secretory phospholipase that confers neuroprotection and cognitive resilience

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

Опубликована: Сен. 3, 2024

Breakdown of lipid homeostasis is thought to contribute pathological aging, the largest risk factor for neurodegenerative disorders such as Alzheimer’s Disease (AD). Cognitive reserve theory posits a role compensatory mechanisms in aging brain preserving neuronal circuit functions, staving off cognitive decline, and mitigating AD. However, identities have remained elusive. A screen hippocampal dentate granule cell (DGC) synapse loss-induced factors identified secreted phospholipase, Pla2g2f, whose expression increases DGCs during aging. Pla2g2f deletion exacerbates aging-associated pathophysiological changes including loss, inflammatory microglia, reactive astrogliosis, impaired neurogenesis, dysregulation hippocampal-dependent memory loss. Conversely, boosting sufficient preserve synapses, reduce microglia gliosis, prevent impairment modify trajectory decline. Ex vivo, neuronal-PLA2G2F mediates intercellular signaling decrease droplet burden microglia. Boosting an aging-sensitive AD model reduces amyloid load improves memory. Our findings implicate PLA2G2F neuroprotective that maintains counteract

Язык: Английский

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Some social issues in DYRK1A model mice stem from faulty inhibitory circuits

The Transmitter, Год журнала: 2023, Номер unknown

Опубликована: Янв. 1, 2023

Язык: Английский

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