Investigating the lateral prefrontal cortex circuitry in the common marmoset

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.