ArticleCNS neuroscience & therapeutics2025
CA3 Pyramidal Neuron Activation Promotes Cognitive Resilience to Inflammation-Induced Cognitive Inflexibility.
Article in CNS neuroscience & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- The Liver-brain Axis: A Three-stage Model Linking MASLD to Cognitive Impairment and Dementia.Journal of molecular neuroscience : MN · 2026Review
- Hepatic HMGCS2-derived β-hydroxybutyrate attenuates hippocampal insulin resistance and neuroinflammation to promote MASLD-induced cognitive function.Communications biology · 2026Article
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Authors and funding
9 authors.
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Abstract
aimsCognitive dysfunction represents a prominent symptom in numerous prevalent mental illnesses, with systemic inflammation induced by cytokines recognized as a critical factor contributing to cognitive impairments. However, a significant proportion of individuals exposed to systemic inflammation do not develop cognitive dysfunction; instead, they exhibit adaptive responses to this adverse condition. This study aims to investigate the neural activity patterns within the hippocampus and the potential mechanisms that mediate cognitive resilience, particularly in the context of inflammation.
methodsWe investigated the effects of systemic IL-1β (Interleukin-1β) on learning, spatial memory, and cognitive flexibility using the Barnes maze test (BMT). We further analyzed specific activity changes in the hippocampus of mice exhibiting cognitive resilience versus susceptibility through immunofluorescence, fiber photometry, and behavioral assessments. Additionally, we employed chemogenetic modulation to explore the role of dCA3 pyramidal neurons in cognitive inflexibility induced by systemic inflammation.
resultsSystemic inflammation induces cognitive inflexibility while leaving learning and memory intact. Notably, dCA3 activity was elevated in cognitively resilient mice compared to their susceptible counterparts. Fiber photometry data revealed higher activity in the dorsal CA3 (dCA3) when the mice approached the previous target quadrant during the reversal stage of BMT. Importantly, the activation of CaMKII
conclusionsActivation of hippocampal dCA3 neurons, rather than dentate gyrus (DG) neurons, enhances cognitive resilience by improving cognitive flexibility during BMT-related paradigm shifting under sustained inflammation.
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