ArticleNature communications2026
Early-Stage Corticostriatal Hyperactivity Impairs Cognitive Flexibility Alongside Striatal Cholinergic Dysfunction in an Alzheimer's Disease Model.
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed.
- Extended Amygdala CRF Projections to Striatal Striosomes Potentiate Dopamine Suppression During Fentanyl Withdrawal.bioRxiv : the preprint server for biology · 2026Article
- Dual-engram architecture within a single striatal cell type distinctly controls alcohol relapse and extinction.Neuron · 2026Article
- Subregion-Specific Input Organization of Prefrontal-Projecting Basal Forebrain Cholinergic Neurons and Weakened Striatal-NBM Inhibitory Transmission in 5xFAD mice.bioRxiv : the preprint server for biology · 2026Article
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12 authors.
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Abstract
Cognitive flexibility declines early in Alzheimer's disease, yet the underlying circuit mechanisms remain unknown. Here, we report that young 5xFAD mice exhibit deficits in instrumental reversal learning prior to spatial memory impairment. This behavioral inflexibility is associated with abnormal neuronal reactivation in the medial prefrontal cortex and dorsomedial striatum. Electrophysiological recordings reveal that medial prefrontal cortex neurons are hyperexcitable and receive increased excitatory input. Furthermore, glutamatergic transmission from the medial prefrontal cortex to striatal direct-pathway medium spiny neurons is enhanced and coincides with strengthened inhibitory transmission onto striatal cholinergic interneurons, reduced spontaneous firing, and diminished striatal acetylcholine release. Critically, sustained chemogenetic inhibition of this corticostriatal circuit attenuates cortical amyloid accumulation, reduces glutamatergic transmission, and increases acetylcholine levels. This also rescues reversal learning deficits in 5xFAD mice. Here, we show that pathological corticostriatal hyperactivity contributes to early cognitive inflexibility in a mouse model of Alzheimer's disease.
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Registered trials
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