Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Doctor of Philosophy

Program

Neuroscience

Supervisor

Everling, Stefan

Abstract

The prefrontal cortex (PFC) is involved in higher cognitive functions, including decision-making, planning, reasoning, and working memory. It is also implicated in several neuropsychiatric disorders, such as attention deficit disorder, schizophrenia, depression, and post-traumatic stress disorder, and is particularly vulnerable to aging and stress. Despite its known role in cognition, the mechanisms by which the PFC produces these functions, such as working memory, remain unclear. Experimental studies using nonhuman primates have significantly advanced our understanding of prefrontal function and, by extension, human cognition.

Our knowledge of the neurophysiological basis of working memory largely comes from research in rhesus macaques. However, the marmoset, a New World monkey, has emerged as a valuable complement to macaque and rodent models for studying the primate brain in both healthy and diseased states. With its smooth cortex, small brain size, and high reproductive rate, the marmoset provides a practical alternative for neuroscience research. Yet, before this work, investigations of working memory in marmosets had been limited to behavioral studies.

The first aim of this dissertation was to identify the neural correlates of spatial working memory in marmosets. We demonstrated that lateral PFC neurons exhibit persistent delay-related activity during a spatial working memory task, establishing the marmoset as a viable model for neurophysiological studies of working memory. Additionally, we examined lateral PFC subregions (8aV, 8aD, 9, 10, 46d, 46v, and 47) by recording neural activity in response to various visual and auditory stimuli and during working memory performance. Task-modulated and neurons responsive to different stimulus modalities were distributed throughout the lateral PFC, with subtle differences across regions.

To further examine working memory, we investigated how marmosets filter distractors in PFC circuits. We found that distractor saliency correlated with task performance and was reflected in delay activity at the single-neuron level. These findings reinforce the marmoset as a suitable model for studying the neural mechanisms of working memory.

Summary for Lay Audience

Our knowledge of how the brain supports working memory largely comes from studies in rhesus macaques. While macaques are excellent for studying complex cognitive functions, they have some limitations. Before this dissertation work, scientists had only studied working memory in marmosets at the behavioral level. It was unclear whether their brain cells (neurons) would show the same patterns of activity seen in macaques during memory tasks.

To investigate this, we implanted microelectrode arrays in the lateral PFC of marmosets. We recorded neural activity while they performed a delayed-match-to-position touchscreen task. We found that neurons in many PFC subregions were active during different parts of the task. For the first time, we showed that marmoset PFC neurons display persistent delay-related activity, similar to macaques.

We also examined how different parts of the marmoset PFC process information. We found neurons that responded to visual stimuli, faces, eye movements, and sounds across multiple brain areas. Some PFC subregions had more of certain types of responses, revealing both shared and specialized functions across the PFC.

Additionally, we explored how marmosets handle distractions during a spatial working memory task. When a distracting stimulus appeared briefly during the delay period, it influenced their performance, and we saw changes in neural activity. Some neurons reduced their response to distractions, suggesting the brain filters out irrelevant information. When this filtering process failed, marmosets made more mistakes.

Overall, our findings confirm that marmosets are a valuable model for studying working memory and brain function. This research helps us better understand memory processes and could contribute to future studies on conditions affecting cognition, such as Alzheimer’s disease and schizophrenia.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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