IRFP: In Vivo Dissection Of Long-Range Cortical Circuits

Chen Jerry L, Boston MA

Investigators

Abstract

The International Research Fellowship Program enables U.S. scientists and engineers to conduct nine to twenty-four months of research abroad. The program's awards provide opportunities for joint research, and the use of unique or complementary facilities, expertise and experimental conditions abroad. This award will support a twenty-four-month research fellowship by Dr. Jerry Chen to work with Dr. Fritjof Helmchen at the University of Zurich, Brain Research Institute in Zurich, Switzerland. A key feature underlying the computational power of the mammalian brain is the processing of neuronal activity occurring simultaneously on multiple levels: from the integration of thousands of synaptic inputs in an individual neuron, to the computations occurring within local circuits, to the feedforward and feedback transmission of disparate streams of information across distant cortical regions. Long-range communication between cortical brain areas is essential for a variety of higher cognitive functions. However, the exact information encoded in these long-range circuits and its relationship to the computation occurring in local neuronal circuits is largely unknown. This project determines how neuronal activity is transmitted and coordinated across distant cortical regions and how this activity influences the processing of information in local circuits. The mouse tactile whisker sensorimotor system is used as a reduced and tractable model to study these cortico-cortical interactions during behavior. Using in vivo imaging technology in combination with molecular and genetic tools, the activity of optically identified long-range range projection neurons are measured and manipulated as mice engage in a trained sensorimotor task. Utilitzing the expertise of the host institute, a novel in vivo imaging system is also being developed that will enable the simultaneous measurement of neuronal activity across cortical areas with single cell resolution. This enabling technology allows neuroscientists to study global brain activity in a manner previously unachievable. The dissection of long-range cortical networks with cellular resolution contributes to a comprehensive understanding of the central nervous system across multiple levels and bridges knowledge gaps between brain region function and cellular physiology. Studying the function of these networks also aids in the understanding of pathologies underlying various cognitive disorders such as Autism Spectrum Disorder, Schizophrenia, and Alzheimer?s Disease where disruptions in anatomical and functional cortico-cortical connectivity are widely recognized hallmarks. Further, this work serves to strengthen and expand already existing, internationally-funded projects in the lab, consisting of collaborations with researchers throughout Europe: the BrainScaleS Project (EU FET-Proactive FP7), the NeuroChoice Project (a Swiss Systems Biology Initiative), and Barrel Cortex Function Project (a joint SNF-DFG grant).