Principles of local synaptic connectivity underlying motor cortical population dynamics

• Applicant: Dr. Yangfan Peng
• Subject Area: Experimental and Theoretical Network Neuroscience
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 563285920

Neural activity is shaped by synaptic connectivity between different neurons. While local excitatory connectivity is highly structured, the specificity of inhibitory connectivity remains under debate. In motor cortex layer 5 (L5), excitatory neurons either project to cortical regions (intra-telencephalic, IT) or to the pyramidal tract (PT). As the main cortical output, these neurons exhibit distinct morphology, connectivity and activity during movements. But how they are synaptically embedded in higher order excitatory and inhibitory networks and how their in vivo activity relates to specific microcircuit organization is unknown. Understanding how connectivity relates to in vivo activity that gives rise to behavior is a central question in neuroscience. We have recently found directed higher order network principles in layer 2-3 of the human cortex that are distinct from previous rodent studies. Furthermore, we and others have found structured and subtype-specific inhibition by interneurons in different cortices. These findings raise the question whether the L5 microcircuit exhibits structured inhibition and to what extent cortical connectivity can be generalized across layers and species. Specifically, we will address the following questions: 1) What is the higher order network structure of excitation and inhibition in L5 motor cortex? 2) How does the L5 microcircuit contribute to movement encoding? 3) Are mouse L5 microcircuit principles generalizable to the human cortex? Addressing these questions will significantly advance our understanding of microcircuit computation in mouse and human cortex L5. Furthermore, it will support our overarching goal of establishing a framework that links ex vivo microscale connectivity with in vivo population dynamics. Achieving this goal is now possible thanks to recent technological innovations, which enable high-throughput recordings of both single neuron connectivity and activity. I will combine my expertise in multi-neuron patch-clamp with in vivo high-density Neuropixels recordings to investigate cortical microcircuit structure and function across species. This will be complemented by state-of-the-art optogenetic tools and the rare access to human brain tissue at the host institution.

• DFG Programme: Emmy Noether Independent Junior Research Groups
• International Connection: Switzerland
• Major Instrumentation: Implantable Electrophysiology setup ; Multi-patch setup upgrade
• Instrumentation Group: 3440 Elektrophysiologische Meßsysteme (außer 300-309 und 340-343)
• Cooperation Partner: Pau Vilimelis Aceituno, Ph.D.