PROJECT SUMMARY/ABSTRACT Working memory, the ability to maintain and manipulate in formation in memory over a period of seconds, is a critical component of higher cognitive functions. Neurons in the prefrontal cortex and other brain areas continue to discharge during the maintenance of working memory however, little direct evidence exists on how neurons of different types organize into functional circuits to subserve these functions. A theoretical proposal, known as the Division-of-Labor model, has proposed that different types of interneurons in the prefrontal cortex play distinct roles with respect to attention. We propose to test the model in an awake, behaving non-human primate model. We will focus on one interneuron type, that expressing somatostatin, which we will identify through viral transfection and optogenetic methods. We will characterize the response properties of SST neurons in awake behaving monkeys performing visual-spatial attention tasks, determine the relative contributions of SST neurons in the local circuit that is activated during the task, and manipulate their activity through optogenetic means. This project will allow us the unprecedented ability to characterize and manipulate a neural circuit that controls a higher cognitive function (working memory) as model of understanding the circuits that underlie higher cognition.

PROJECT NARRATIVE This project will rely on a non-human primate model to investigate the role of neural circuits in the prefrontal cortex that mediate working memory. Working memory is compromised in conditions such as stroke and traumatic brain injury, as a result of normal aging, and in neurodegenerative diseases including Alzheimer’s disease. Our results will uncover the brain circuits responsible and offer insights on the design of better treatment strategies for dealing with cognitive decline associated with these conditions.