This PhD project will investigate how the auditory thalamocortical circuit contributes accurate to learning and perception by examining its synaptic plasticity and dynamic regulation during behavior. Using two-photon calcium imaging in mice performing auditory discrimination tasks, we will track activity in thalamic inputs and cortical neurons across different learning stages to reveal how experience shapes circuit function. A schizophrenia pathology–related mouse model will be used to identify alterations in thalamocortical communication associated with impaired perception. In a second phase, targeted modulation of thalamic activity will test its causal influence on cortical plasticity and behavioral adaptation. Together, these studies will uncover fundamental principles governing how thalamic input drives cortical learning, providing mechanistic insight into the cellular basis of adaptive cognition.

Background and Rationale
Learning and memory rely on the brain’s capacity to modify synaptic connections and dynamically adjust information flow across cortical and subcortical networks. The thalamus plays a critical role in these processes by regulating how sensory signals are integrated, filtered, and relayed to cortical areas. Beyond its traditional role as a sensory gateway, the thalamus participates actively in higher-order functions such as associative learning, contextual modulation, and cognitive flexibility.
Within the auditory system, the secondary auditory thalamocortical (2ATC) pathway — linking the auditory thalamus (AT) with the secondary auditory cortex (2AC) — is a central hub for integrating sensory experience with learned associations. This circuit also communicates extensively with limbic and frontal regions, positioning it as a key structure for transforming perceptual input into memory and decision-relevant representations.
Alterations in thalamocortical communication and excitatory–inhibitory balance have been observed in several conditions associated with impaired sensory integration and cognitive deficits, including schizophrenia. Understanding the synaptic and circuit mechanisms that underlie these disturbances could inform strategies for circuit-level interventions, but fundamental questions remain about how thalamocortical plasticity supports normal learning and memory processes.
This project will therefore investigate how activity-dependent plasticity within the auditory thalamocortical circuit contributes to associative learning, and how its disruption in a schizophrenia pathology–related mouse model affects information processing and behavioral adaptation.

Hypotheses and Objectives
We hypothesize that the auditory thalamocortical circuit exhibits bidirectional plasticity that encodes learning-related changes in stimulus–outcome associations, and that disruption of this mechanism leads to altered sensory and cognitive performance. We further propose that targeted modulation of thalamic input can influence cortical plasticity and behavioral outcomes, revealing causal links between thalamic dynamics and learning efficacy.
To address these hypotheses, the project is organized into two experimental aims.

Aim 1 – Characterizing Thalamocortical Plasticity During Auditory Learning
The first aim seeks to define how synaptic and circuit-level plasticity within the 2ATC pathway evolves during associative learning. Mice will be trained in an auditory Go/No-Go discrimination task where specific tones predict rewarding or aversive outcomes. Using two-photon calcium imaging, we will record activity from presynaptic boutons of thalamic projections and postsynaptic dendrites of cortical neurons during task performance.
This approach will allow longitudinal tracking of structural and functional plasticity across different phases of learning — acquisition, consolidation, and reversal. By comparing activity patterns between control animals and a schizophrenia pathology–related mouse model, we will determine how changes in synaptic strength and coordination reflect learning performance and memory flexibility.
The analysis will focus on how thalamic inputs shape cortical representations over time, and how their modulation corresponds to behavioral indices such as discrimination accuracy, response latency, and learning speed. These results will establish a cellular and functional map of thalamocortical plasticity during auditory learning.

Aim 2 – Causal Modulation of Thalamic Activity and Its Impact on Learning and Plasticity
The second aim will test the causal contribution of thalamic activity to cortical plasticity and learning behavior. To this end, we will combine two-photon imaging with focal electrical stimulation of the auditory thalamus during behavior.
By systematically varying stimulation timing and frequency, we will assess how enhanced or suppressed thalamic drive influences cortical dynamics and behavioral performance. Longitudinal imaging will reveal whether specific patterns of thalamic activation can promote functional synaptic remodeling in the auditory cortex, thereby accelerating or stabilizing learning.
In parallel, we will compare these effects between control and schizophrenia pathology–related models to determine whether circuit-level interventions can compensate for impaired plasticity. This aim will thus provide mechanistic insight into how thalamic input regulates cortical learning rules and whether this regulation remains flexible under altered network conditions.

Expected Outcomes and Significance
This project will elucidate fundamental principles of thalamocortical plasticity in learning and memory. Specifically, it will:
1. Define how coordinated synaptic changes in the auditory thalamocortical circuit underlie associative learning.
2. Identify how circuit dysfunction affects sensory–cognitive integration in a validated model of schizophrenia-related pathology.
3. Establish causal evidence that modulation of thalamic activity can influence cortical plasticity and behavioral adaptation.
Beyond its relevance to auditory processing, the project will contribute broadly to our understanding of how thalamic circuits support flexible learning and memory formation. These findings may also provide a mechanistic foundation for future circuit-based interventions targeting cognitive and perceptual disturbances, though the primary focus remains on basic neurophysiological mechanisms.