Deciphering top-down encoding in sensory thalamocortical pathways: implications for schizophrenia

Perception is a process by which the brain integrates bottom-up sensory information with top-down signals shaped by learned associations, expectations, and task demands. Imbalances between these processes may contribute to perceptual alterations in schizophrenia, yet the circuits implementing top-down information remain unclear. Previous work showed that higher-order auditory thalamic (HOAT) projections convey learned aversive-value signals to secondary auditory cortex (A2). We hypothesized that these pathways shape sensory representations according to learned associations and task demands. Using an auditory-cued Go/No-Go task, we found that selective silencing of HOAT output impaired task acquisition, showing a role in associative learning. Longitudinal two-photon calcium imaging of HOAT axonal boutons in auditory cortex revealed learning-related changes and distinct functional populations, indicating plasticity and encoding beyond stimulus acoustics. We next hypothesized that Go/No-Go learning is altered in a mouse model with schizophrenia-like phenotypes, reflecting impaired updating of internal models. Preliminary data show reduced task acquisition and altered perceptual thresholds in SCZ mice compared with controls. Together, these findings support a role for HOAT circuits in shaping sensory processing according to learned and internally generated information, suggesting that their disruption may contribute to altered perception in schizophrenia-like states.