Research in the CNSL focuses on the regulation and function of a major component of the brain’s attention systems, the cortical cholinergic input system. We are specifically interested in understanding what cognitive processes are mediated via fast or “transient” cholinergic signals, and how we can use this knowledge to enhance and restore cognition in healthy subjects and patients, respectively.
Our research utilizes a wide range or neuroscientific methods, including sophisticated electrochemical techniques to monitor synaptic signaling in performing rodents, optogenetic methods and DREADDs to control different aspects of cortical cholinergic activity and cortico-striatal glutamatergic signaling, and genetic approaches to vary the capacity of cholinergic neurons to sustain elevated levels of neurotransmission.
We conduct parallel and converging research in rodents and humans, to validate and expand our conclusions from animal models, and to determine the relevance of our basic research in animals for human cognition and cognitive disorders. The Table below summarizes our basic and translational research projects and it illustrates the parallel strategies of research in rodents and humans.
For example, in mice, we are studying the impact of the expression of human subcapacity variant of the choline transporter (CHT; I89V variant). The CHT strongly influences levels of cholinergic neuromodulation and thus biases toward bottom-up versus top-down attentional control. In rodents, we use state-of-the art electrochemical methods to monitor the activity of cholinergic neurons during task performance, and while we are controlling cholinergic activity using optogenetic and chemogenetic methods. In humans, we are studying the impact of genetic variations of the CHT on attentional performance and underlying brain systems, and the risk of such variations for attentional disorders. See Research for more details.