Functions of Mediodorsal Thalamic Astrocytes in Cue-Based Learning

To successfully navigate daily life, organisms must be able to identify stimuli that are predictive of beneficial outcomes. A key thalamic nucleus involved in this process is the mediodorsal thalamus (MD), which bidirectionally communicates with the prefrontal cortex, facilitating cognitive and decision-making functions. Despite the MD's involvement in higher-order relays, the precise mechanisms underlying its astrocytic activity, its contribution to synaptic plasticity, and the subsequent effects on cognitive processing remain poorly understood. Emerging data highlights the pivotal role of astrocytes in regulating synaptic transmission, with astrocytic calcium activity being linked to gliotransmitter release. Abnormalities in astrocytic calcium activity have been found to impair learning and memory, thus insights into their mechanism during cognitive processes in the MD could reveal novel targets for investigating cognitive disorders. In this study, we investigated astrocytic activity during a cue-based learning task, uncovering notable differences in the timing of astrocytic calcium release between early and late stages of the task. To investigate plasticity-related changes between early and late stages, the density of astrocytes, glutamatergic nerve terminals, and astrocyte glutamate transporter proteins will be examined. We found that MD astrocytic calcium activity responds to the initial cue and the reward, suggesting that this activity mediates the temporal dynamics of synaptic plasticity, influencing how thalamic circuits adjust to both cues and outcomes during learning.