High resolution imaging of cortical activity during cognitive function
Abstract
Neuroscientists have long sought to understand how neurons in many regions form long-range circuits and contribute to complex cognitive functions. However, at present few labs are able to record activity from more than 1,000 neurons simultaneously, and those recorded neurons are often confined to a small fraction of cortical surface. In this proposal we describe equipment that will enable us to image tens of thousands of neurons across the entire cortex, in conjunction with equipment for subcortical recordings. These capabilities will enable us to study many complex cognitive functions in an integrated fashion for the first time. This equipment is meant to support research that will be described in more detail in a forthcoming application to AFOSR. This proposal requests funds to build a novel and transformative imaging system, which we call Widefield Imaging of Sparsely Labeled Cortex (WISLaC). WISLaC employs sparse labels, a large optical window, a new type of magnetic actuator, and sophisticated image processing, to enable high speed high-resolution fluorescence imaging of the activity of many thousands of individual neurons across one hemisphere or the whole dorsal surface of mouse cortex. The system will record fluorescence over the whole cortex by mounting a macroscope objective lens on a rapidly moving actuator to enable rapid interleaved imaging in several distinct focal planes, each several times per second. This system may be used to record cortical activity in one hemisphere together with electrical probes measuring simultaneous activity in sub-cortical regions of that half of the brain. The system will record activity of tens of thousands of individual neurons from up to three distinct intermingled populations of cortical neurons over the extent of dorsal cortex. These populations will be excitatory neurons in cortical layer 2/3, excitatory neurons in layer 5 or layer 6, and interneurons across cortical layers. This technology will allow us to study how groups of neurons in different cortical regions communicate with each other during cognitive tasks, and how cortical activity is coordinated with neural activity in key subcortical regions, such as thalamus, hippocampus and basal ganglia. Furthermore, the sparse labeling makes it feasible to re-identify neurons and to document the specific changes in activity and in cross-cortical communication during learning. We plan to use this system to investigate several distinct cognitive functions. First, we will investigate the circuitry involved in the popular paradigm of association learning. We will measure the activities of neurons across the cortex during learning and characterize the changes in correlations between specific subnetworks of neurons in frontal, parietal, and sensory regions. Then we will investigate how animals learn to make sharp discriminations between similar auditory or visual stimuli, by studying the interactions between sub-networks of neurons in frontal and in sensory regions during sensory discrimination learning. We will also study the interactions between sub-networks of neurons in sensory and motor cortex, and their relation to activity of striatal neurons, during motor skill learning. We will also study higher order cognitive functions. We will investigate how specific subnetworks of neurons in frontal regions change their relationships to representations of activity in sensory regions, as an animal learns a more complex task integrating several diverse cues. This approach may be extended to neurons in deeper brain structures as red-shifted fast indicators become available. Furthermore, such recordings can be readily integrated with imaging methods that reveal cell types by in-situ gene expression, characterize projections, or assay molecular processes.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Feb 29, 2024
- Source ID
- FA95502310047
Entities
People
- Mark Reimers
Organizations
- Air Force Office of Scientific Research
- Michigan State University
- United States Air Force