Roles of parvalbumin-expressing neurons in primate cortical processing

University Of Washington, Seattle WA

Investigators

Abstract

PROJECT SUMMARY/ABSTRACT Inhibitory neurons likely underlie many neural computations. They are highly conserved in neural circuits throughout the brain and their dysfunction has been implicated in many neurological and psychiatric disorders. But very little is known about how they contribute to neural computations, especially in the primate brain. An important computation that inhibitory neurons likely mediate is gain control. Gain control is the process by which neural sensitivities are adjusted so firing rates stay within their dynamic ranges without altering stimulus selectivity. Gain control exists throughout the brain, but it is especially well-characterized in the visual system, where it can contribute to many processes such as contrast-invariant orientation tuning, attention, and multisensory integration. A type of inhibitory neuron likely specialized for gain control is parvalbumin expressing (PV+)-neurons. Optogenetically activating PV+ neurons in mouse primary visual cortex (area V1) represses the responses of excitatory neurons without altering their orientation selectivity. However, it is unknown if PV+ neurons in primates modulate their targets in the same way because of the lack of genetic tools that enabled the mouse experiments. Fortunately, recent advances in viral genetic tools now allow for selective targeting of PV+ neurons in macaques. In the proposed research, we will use these tools to determine if PV+ neurons in the primate brain mediate gain control. Aims 1 and 2 are to determine if PV+ neurons are specialized for gain control by activating/inactivating them optogenetically and measuring their effects on excitatory neurons. Additionally, many models of gain control make predictions about the tuning of PV+ neurons. Some models predict that PV+ neurons are broadly tuned, while others predict they are tuned similarly to their excitatory counterparts. Aim 3 is to determine which type of model is more accurate. PV+ neurons will be identified by their responses to optical stimulation, then their orientation tuning will be compared to excitatory neurons. For all these experiments, cell-type specific optogenetics and high-density Neuropixel recordings will be paired in primates, which will allow for extremely high-throughput characterization of specific cell-types. This work is a crucial step towards understanding the roles of PV+ neurons in the primate brain and how they contribute to cortical processing. This improved understanding will in turn pave the way for future treatments of diseases associated with PV+ neurons. The proposed research will also provide valuable training in neurophysiology, optogenetics, hardware engineering, and data analysis. Moreover, it will support professional development by providing opportunities for scientific communication, mentorship, and teaching. This research will be conducted at the University of Washington under the supervision of Dr. Gregory Horwitz, who has significant experience with primate physiology and optogenetics. This work will also benefit from the support of other faculty members and the resources of the Washington National Primate Research Center.