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FRIBIO-Biologi og biomedisin

Electrical signaling in thin dendrites and axons in the cortex

Awarded: NOK 2.5 mill.

A major challenge in neuroscience is to understand the mechanisms of neuronal computation, much of which is carried out by electrical signals generated by ion channels in the cell membrane. Within the last decade, advances in patch-clamp and imaging techn iques have extended our knowledge of such mechanisms into the smaller, sub-cellular domains. Accumulating evidence suggests that thin dendritic branches, such as the oblique dendrites and tufts of cortical pyramidal neurons, can execute local integration and "binary computations", due to the presence of dendritic ion channels. Furthermore, two recent publications showed that axons in the mammalian cerebral cortex transmit not only "all-no-none" action potentials but also subthreshold analogue signals, whi ch can strongly modulate synaptic output from axon terminals. These novel mechanisms are likely to greatly enhance the computational power of our nervous system. However, our understanding of these processes has been limited by difficulties to obtain elec trical recordings directly from thin neuronal structures. In this project, we will use fluorescent video microscopy-guided patch-clamp recording from thin dendrites and axons in the cortex to study their electrical signaling mechanisms. The project will f irst focus on establishing new methods for patch-clamp recording (loose-patch, cell-attached and, when possible, whole-cell recording) from thin neuronal structures. Next, we will study (1) the mechanisms regulating sub-threshold axonal propagation, (2) t he ionic mechanisms regulating local spikes in thin dendritic branches, and (3) the contribution of three types of K+ channels (BK, SK and KCNQ/Kv7/M channels) to the excitability of the apical dendrite of cortical pyramidal neurons. Computational simulat ions, using detailed, conductance-based, multi-compartmental models of pyramidal neurons, will be performed in parallel with the experiments.

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FRIBIO-Biologi og biomedisin

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