FROM UNSTABLE LANDMARKS TO FALSE BELIEFS: HIPPOCAMPAL INFORMATION PROCESSING IN MK801 PSYCHOSIS MODEL

Schizophrenia and schizoaffective disorder are characterized by disrupted information processing and aberrant network kinetics, resulting in impairments of attentional control or cognitive flexibility. In dynamic environment conditions subjects rely primarily on stable cues while downweighting the unstable ones. Overreliance on unstable cues may cause increased representation instability that might lead to misinterpretation of reality and formation of false beliefs. Here, we investigated the effects of changes in cue stability on spatial representations in psychosis. To mimic a rapidly changing environment, rats were exposed to square arena in which the dominant visual cue on one of the walls was abruptly switched to an adjacent wall, corresponding to a 90° shift. We used MK-801 (0.05mg/kg and 0.1mg/kg), an NMDA-receptor antagonist, to model psychosis-like state. Rats were implanted with tetrodes targeting hippocampal CA1 and habituated to the arena with one stable light cue. Subsequent recordings were conducted under control and MK-801 conditions and consisted of stable template sessions followed by a rotation session with multiple 90° cue shifts. We assessed spatial representation stability by comparing place cells firing fields between template and rotated cue placement across both conditions. Under control and 0.05mg/kg MK-801, place cells maintained stable template representations independent of cue location, indicating appropriate disregard of unstable sensory inputs. In contrast, under 0.1mg/kg MK-801, most cells altered their firing fields in accordance with the light cue rotation. This indicates a shift in relevance between perceived sensory cues and may reflect a neural correlate of false belief formation. Supported by GACR-26-23770S and SVV-263774.