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Schlagwörter:
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Zusammenfassung:
The rodent whisker system is a unique model to investigate mechanistic principles of sensory information processing. Unfortunately, monitoring of whisker-evoked excitation streams, at millisecond timescales and subcellular resolution, remains experimentally impossible. Thus, we pursue an alternative approach by reverse-engineering the 3D structure and cell type-specific function of rat vibrissal thalamus and cortex. First, we perform single neuron recordings in vivo, to map sub-threshold and spiking receptive fields (RF), evoked by principal and surround whisker deflections. Second, we recover the detailed 3D dendrite/axon morphologies of the in vivo characterized neurons. Cluster analysis reveals 9 excitatory cell types across cortical layers 2-6; each type displaying characteristic morphological and sensory-evoked functional properties. Third, we developed a precise 3D reference frame that allows registering anatomical data obtained from many animals into a standardized cortex. Fourth, the measured 3D distribution of all excitatory/inhibitory somata in rat vibrissal thalamus and cortex, as well as the detailed 3D neuron reconstructions are integrated into the standard cortex. This reverse-engineering approach results in an anatomically realistic model of the entire rat barrel cortex, where each of the ~500,000 neurons is represented as a full-compartmental model and a subcellular distribution that specifies its synaptic innervation. Finally, the resultant barrel cortex ‘Connectome’ is used to investigate relationships between whisker-evoked RFs and the structural organization of the neural circuits. We find that the reverse-engineered synaptic innervation patterns, convolved with the whisker-evoked spiking activity allow predicting the sub-threshold RFs for each excitatory cell type. Further, at the single cell level, simulation experiments reveal cellular and network mechanisms underlying whisker-evoked excitation, by comparing the ‘in silico’ predictions with the previously measured responses in vivo. The present framework of the barrel cortex ‘Connectome’ renders the starting point for linking the synaptic organization of neural circuits to functional mechanisms of sensory information processing - for the first time providing insights into the complex origin of neuronal RFs.
