DECIPHERING TOP-DOWN ENCODING IN THE THALAMOCORTICAL PATHWAY

Perception arises from the interaction between bottom-up sensory inputs and internal models built from prior experience. Perceptual judgments can thus be understood as decision-making processes that aim to minimize errors by integrating sensory evidence with prior expectations. Higher-order sensory thalamocortical circuits are well suited to study this interaction, as they lie at the interface between sensory processing and higher cognitive functions. Our previous studies using threat conditioning paradigm have shown that auditory higher-order thalamic pathways convey top-down signals related to learned stimulus negative value to secondary auditory cortex.
Here, we hypothesize that in a decision-making context, higher-order thalamocortical circuits convey decision-related information, integrating prior experience, task rules, and expected outcomes to guide action selection. To test this, we employed an auditory-cued Go/No-Go task. First, we combined it with selective silencing of higher-order thalamic output using a Cre-dependent strategy. Animals with disrupted higher-order thalamic transmission failed to acquire the task, indicating a deficit in associative learning.
To investigate the cortical consequences of higher-order thalamic silencing, we performed histological analyses in the secondary auditory cortex, the main cortical target of higher-order auditory thalamus. Finally, to examine the real-time contribution of higher-order thalamic inputs to top-down encoding during behavior, I performed longitudinal two-photon calcium imaging of thalamocortical axons projecting to layer 1 of the secondary auditory cortex throughout Go/No-Go task acquisition.
Together, these results highlight the importance of auditory higher-order thalamocortical circuits for top-down modulation that supports accurate perception.