biostudies-literatureAtilgan HWellcome TrustEC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)10767https://www.ebi.ac.uk/biostudies/studies/S-EPMC12663370biostudies-literatureUnknown16(1)The claustrum is a densely interconnected structure involved in cognitive functions, but its influence on prefrontal circuits remains unclear. We conducted two-photon calcium imaging to assess mice dorsal prefrontal cortex (dPFC) cell responses during exposure to visual stimuli and widefield photostimulation of claustrum axons embedded in the dPFC. We identified three distinct subpopulations of neurons - sensory responsive, opto responsive, and opto-boosted cells-each exhibiting unique response dynamics to combined visual and optogenetic stimuli. Our findings reveal that claustrum stimulation increased single-cell variability while aligning average responses across neurons, thereby enhancing network homogeneity. During Pavlovian training, enhanced variability persisted, but homogeneity incNature communicationsThe claustrum enhances neural variability by modulating the responsiveness of the prefrontal cortex.PMC12663370852765213465/Z/18/Z204651/Z/16/ZLazarte IPPacker AMAtilgan HfalseThe claustrum enhances neural variability by modulating the responsiveness of the prefrontal cortex.The claustrum is a densely interconnected structure involved in cognitive functions, but its influence on prefrontal circuits remains unclear. We conducted two-photon calcium imaging to assess mice dorsal prefrontal cortex (dPFC) cell responses during exposure to visual stimuli and widefield photostimulation of claustrum axons embedded in the dPFC. We identified three distinct subpopulations of neurons - sensory responsive, opto responsive, and opto-boosted cells-each exhibiting unique response dynamics to combined visual and optogenetic stimuli. Our findings reveal that claustrum stimulation increased single-cell variability while aligning average responses across neurons, thereby enhancing network homogeneity. During Pavlovian training, enhanced variability persisted, but homogeneity inc2025-01-01T00:00:00Z2025 Nov2026-06-05T21:25:25.534Z2026-05-22T03:08:59.942ZS-EPMC126633704131521510.1038/s41467-025-65809-6