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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Functions of Mediodorsal Thalamic Astrocytes in Cue-Based Learning

Marschalko, Kathleen Rose 25 February 2025 (has links)
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. / Master of Science / Cognitive abilities are highly regulated by activity present in the mediodorsal thalamus, which is an area of the brain largely responsible for learning and decision making. Cognition has been primarily studied in the context of specific neuronal pathways. However, neurons are supplemented by other cell types in the brain called glia, the most abundant of which are astrocytes. Astrocytes help connect specific neurons together to form synapses. During the process of learning, new synapses can make new connections in a phenomenon called synaptic plasticity which is highly mediated by astrocytes. This activity of astrocytes in the mediodorsal thalamus has not been studied sufficiently. We measured the MD-specific astrocytic activity in real time during a cue-based learning task using a technique called fiber photometry. We also recorded instances of reward seeking behavior characterized by a light cue signaling an upcoming reward. We found that during early learning, astrocytic activity peaked around the onset of the light cue whereas during late learning, astrocytic activity peaked after reward onset. We began to visualize the thalamus excised from animals that completed 0-10 days of the learning task. Our goal with this data is to determine if the number of astrocytes and other proteins that are involved in synaptic plasticity increase with increased learning experience. We are able to suggest that astrocyte activity in the mediodorsal thalamus regulates the changes in patterns of synaptic activity, thereby impacting the ability to learn.

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