"Brain diseases are taking an increasing toll on aging European Societies, and being able to cure them and limit the costs and the social exclusion they generate is advocated by many European policies. Yet, due to its enormous complexity, the brain is the least understood organ of all. Importantly, in order to be able to treat a malfunctioning brain we first need to understand how a normal brain works, which requires that we first crack the neural code, i.e. the language neurons use to encode and transfer the information they receive from the external world.
To address this question much effort has been devoted to record the responses of cortical sensory areas to experimentally controlled stimuli and to build a “dictionary” that can be used to understand how an external event is encoded in the activity of a neural population. Although this so-called “Rosetta Stone” approach has provided much knowledge about the neural code in the past decades, it suffers from three important limitations. First, neurons are noisy: the very same external stimulus can elicit different responses on a neural population, which makes difficult to tear apart what is noise from what constitutes relevant information. Second, to fully describe neural population activities an enormous number of variables –that increases exponentially with the number of neurons- are needed. Third, the ""Rosetta Stone"" approach does not address the question of whether a putative neural code that carries some sensory information is then transmitted to downstream networks.
For these reasons, we need to complement statistical approaches like the “Rosetta Stone” with more direct, causal, techniques that allow manipulating the activity of specific sub-populations of neurons. Recently developed optogenetics approaches allow controlling the neuronal activity using light-gated proteins, and therefore provide a way of testing the role of a specific encoding strategy by applying appropriate stimulation protocols to a population of neurons and evaluating the effects of such stimulation, for instance on a post-synaptic network. However, to be correctly applied to neuroscience experiments these techniques need to be complemented by novel theoretical developments that: 1) identify hypotheses about the encoding strategies used by the neural population under study; 2) create stimulation protocols specifically designed to test the identified hypothesis."
