The impact of stress on the neurobiology of cognition
Abstract
The current view of the brain is that higher cognitive functions such as attention and working memory likely involve coordinated actions of large numbers of neurons. Stress can induce substantial changes in brain activity, both in terms of where in the brain and to what degree, yet little is known of how stress impacts these cognitive processes and underlying neural dynamics. While mammalian learning paradigms have long served as test beds for studying cognition and the impact of stress on it, our inability to measure brain-wide neural activity in such systems has been a major hindrance. Here, we propose to take advantage of the neurogenetic tractability of Drosophi-a and build on our recent work to study these cognitive control mechanisms under two principal associative learning paradigms - delay and trace conditioning. Trace conditioning relies on the ability to hold a stimulus trace ""in mind"" during the time interval between the end of the conditioned stimulus (CS) and onset of the unconditioned stimulus (US), distinguishing it from classical delay conditioning, where the CS and US overlap. Trace conditioning is therefore directly relevant to higher cognition, especially due to its sensitivity to distractions during that interval and has been proposed as a paradigm for attention and working memory in mammals including humans. The neural mechanisms underlying these two learning paradigms, and the impact of acute and chronic stress on these cognitive tasks will be tested in vivo at the level of individual brain regions using two-photon imaging and the whole brain using holographic microscopy. Finally, we will develop new hyperbolic geometry-based methods for the examination of such high-dimensional and dynamically changing large-scale neural activity, uniquely suited as they naturally approximate the hierarchically organized structure of the (fly) brain and characterize the dynamics of neural manifolds that occur with different forms of learning.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Feb 22, 2024
- Source ID
- FA95502310024
Entities
People
- Dhruv Grover
Organizations
- Air Force Office of Scientific Research
- United States Air Force
- University of California, San Diego