The brain processes information through coordinated neuronal activity. This project proposal is aimed at unraveling the coding principles for sensory input by leveraging on three recent technological advances: two-photon imaging, optogenetics and holographic two-photon stimulation. These provide crucial advantages over existing methodology: (i), the use of two-photon imaging allows recording of neuronal activity with single-cell resolution from hundreds of neurons simultaneously; (ii) optogenetic tools permit one select cell type to be both observed and manipulated concurrently in order to probe its specific function in the circuit; and (iii) holographic two-photon stimulation enables the simultaneous manipulation of large numbers of neurons in three-dimensional optical patterns.
The neuronal coding strategies used in somatosensory processing in the neocortex can be studied by combining these techniques. The project will address the long-standing question of whether primary sensory input is encoded by the overall amplitude (rate code) or the precise timing (temporal code) of neuronal activity. Specifically, we will measure neuronal activity evoked by a somatosensory discrimination task in head-fixed, awake, behaving mice using expressed fluorescent calcium ion sensors. We will then employ genetically encoded, light-sensitive ion channels to selectively activate sets of identified neurons. By recording the effect of these manipulations on neuronal activity and task performance, we will determine to what extent rate and temporal codes are necessary and sufficient to represent primary sensory input.
Taken together, these experiments will allow us to quantify the relative importance of rate vs temporal codes in somatosensory perception. Although we will conduct our experiments in the rodent somatosensory cortex, the all-optical approach outlined here is likely to become central for the study of other sensory modalities and cortical function in general.
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