Periodic Reporting for period 2 - PrefrontalMap (Organization and learning-associated dynamics of prefrontal synaptic connectivity)
Reporting period: 2020-08-01 to 2022-01-31
The prefrontal cortex is one of the most densely interconnected regions of the mammalian brain, as it needs to perform countless actions related to cognitive function, memory storage, regulation of emotional states and rapid adaptations to a rapidly changing environment. While we know quite a bit about the wiring of simpler cortical regions, such as those in charge of processing vision, touch or audition, we know relatively little about how associative regions such as the prefrontal cortex are organized, how their neurons connect with one another, and how this connectivity pattern changes with experience and following traumatic events. In PrefrontalMap, we aim to decipher the detailed connectivity map of the prefrontal cortex, and follow the changes in the connectivity of this region that occur during both positive and negative emotional experiences. Using cutting-edge optogenetic technology in animal models, aimed at stimulating and recording single neurons in the prefrontal cortex, we aim to uncover the principles of synaptic organization in this region.
During the first stage of the project, we developed a set of techniques and approaches that allow robust and highly reliable single-neuron optogenetic stimulation in parallel with electrophysiological recordings to reveal the input structure of single neurons in the prefrontal cortex of mice. We focused our efforts on the cells projecting from the prefrontal cortex to the amygdala, another brain region that is crucial for emotional processing, learning and memory. We were able to describe with great detail how these neurons interact with one another and with other neurons in this circuit, paving the way for an investigation of how these connections change over time and with behavioral experience.
During the second phase of the project, we aim to describe with unparalleled detail the organization of connections among prefrontal neurons projecting to key centers in the brain involved in learning from rewards and punishment, and how these connections reorganize with learning. We are also investigating how local-circuit inhibitory neurons influence the dynamics of this circuit, and how their activation or suppression alters the process of learning. Using a custom-built holographic microscope, we will soon be able to perform single-neuron optogenetic control in the living brain and ask how manipulating the activity of defined neurons alters the behavioral performance of animals engaged in complex learning tasks, and whether the brain can be "trained" to respond to information introduced into the circuit through such high-resolution stimulation.