Visualizing cholinergic neuromodulation in vivo using optogenetics and fMRI in monkeys

• Applicant: Jose Daniel Zaldivar Perez, Ph.D.
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; Human Cognitive and Systems Neuroscience
• Term: from 2017 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 392021668

The focus of this project is to investigate the cholinergic neuromodulatory system originating from the basal forebrain (BFB), as well as to understand the intrinsic dynamics and functional role of such modulation during sensory stimulation and cognitive tasks. Although certain features of the cholinergic neurons in the BFB have been studied in detail, including their coarse distribution of anatomical projections, their brain-wide functional roles remain poorly characterized, particularly in primates. This gap in knowledge can be ascribed to a lack of experimental techniques allowing for (1) mapping of cell-type specific anatomical projections, and (2) systematically specifying the intrinsic dynamics and spatial distribution of these projections across distributed brain networks. Ultimately, a deeper understanding of these prominent neural projections, which are thought to play an important role in regulating brain states, attention, and cognitive processing, requires experiments that probe and manipulate select circuit elements. Here, we propose experiments in macaques that combine optogenetic modulation of controlled neural populations in the BFB with whole brain functional magnetic resonance imaging (fMRI) and multisite laminar neurophysiological recordings. This convergence of methods promises to shed new light on the functional contributions of BFB cholinergic projections neurons across large regions of the brain. Studying this topic in non-human primates is critical since the cellular composition of the BFB and granular prefrontal cortex in monkeys resembles the human but differs substantially from the rodent. Combining the selective manipulation of cholinergic circuits with targeted measures of primate behavior and neurophysiology and appropriate computational analysis will allow us to address specific mechanistic hypotheses about how the cholinergic system regulates important aspects of human cognition.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: David A. Leopold, Ph.D.