Dendritic computation during hippocampal network oscillations

The brain is an enormous network of neurons that connected by axons. Axons are long neuronal processes that carry information from the cell body to synapses where individual neurons communicate with each other. Thus, the axon works as the main output structure of a neuron, and knowledge of how information is processed in the axon is critical to understanding how the brain works. However, the small size of axons in the brain represents as a technical challenge for a detailed functional analysis. The cortical neuronal network consists of excitatory principal neurons and inhibitory interneurons. I will study the axon of inhibitory interneurons in the brain. As their name implies, these neurons inhibit other nerve cells. Thus, they regulate the excitability of the neuronal network, and their dysfunctions often cause epilepsy. Interneurons also have a central role in information processing in the brain. They coordinate how information, which is largely carried by the activity of excitatory neurons, flows within the neuronal network in space and time. To understand these functions, it is important to study the properties of interneuron axons. I will focus on the parvalbumin-expressing GABAergic basket cells, which represent one major type of inhibitory interneurons in the cortical network. These interneurons play a number of important roles in functions of the brain. Many of these functions depend on the fast signaling in the interneuron axons. The goal of this project is to unravel the mechanism underlying this remarkably rapid signaling in the interneuron axon with a combination of advanced electrophysiological, imaging techniques and computer modeling methods. The proposed research plan will expand our knowledge of the design logic behind the fast information processing in the nervous system. Furthermore, our data will provide important building blocks for constructing computer models of neuronal network in the brain.

This application aims to develop an ambitious and yet feasible collaborative project to analyze dendritic computation during rhythmic activities of the brain. A functional hallmark of the brain is its rhythmic activity. Brain rhythms are generated by the synchronized firing of many nerve cells in the network, and these oscillatory activities play a key role in neuronal coding and higher cognitive processes. To produce synchrony during rhythmic activities, nerve cells in the network translate synaptic inputs in their dendrites into action potential output in the axon with high temporal precision. But the mechanism underlying this temporally precise input-output operation is not well understood, because dendrites and axons of nerve cells in the mammalian brain are very thin and nearly inaccessible to functional analyses. Consequently, studying dendritic computation during neuronal network oscillations represents a long-standing technical challenge in neuroscience. To face this challenge, the Synaptic Signaling group at the University of Oslo and the Neurophysiology group in Heidelberg will take advantage of their complementary expertise to jointly address a question of their common interest: how is information processed in the dendrites of hippocampal neurons during neuronal network oscillations? To maintain a long-term collaboration, we will take the opportunity provided by the DAAD mobility grant to prepare a collaborative European Research Council (ERC) synergy grant. The collaboration is expected to produce a strong synergistic effect to accelerate our research of how neuronal oscillations organize the formation, storage and retrieval of memories at the subcellular level, which represents a key question at the frontier of neuroscience. Further details are described in the project description found in the attachments.