By using these new methods and strategies, we made several fundamental discoveries (published or submitted to high-profile journals) that have significantly advanced the field of decision-making beyond the state of the art. Notably, we demonstrated the key and intricate function of disinhibition, nonlinear dendritic integration of coincident cortico-cortical and subcortico-cortical input streams in cortical superficial layer, and the trafficking of AMPA receptors in the induction of synaptic plasticity in vivo (Neuron 2019), the initiation of cortical remapping and adaptive behaviors (Cell Reports 2020; PNAS 2021), learning (eLife 2020) and development (Cell Reports 2022). Showing that dendrites are able to generate local computations that influence how animals perceive and adapt to the world, and by which mechanisms, is a break-through in neuroscience, since in the past they were mostly seen as passive elements of the neurons, just funneling information to the soma. Importantly, we found that the firing rates of superficial M2 neurons is gradually modified over long-time scale during reinforcement learning of a foraging task, in a way that quantitatively reflects decision-value, which we found to be dynamically gated by superficial inputs from the basolateral amygdala (eLife 2020). Taken together, our data indicate that M2 pyramidal neurons are indeed critical for action-selection and decision-value signaling.
Key aspects of several psychiatric and neurological disorders involve disturbances of action-selection and decision-value signaling: Parkinson's disease, Tourette's syndrome, attention/hyperactivity disorder, drug addiction, Schizophrenia. Therefore, understanding the neural substrates of decision will tackle medical, societal and economical challenges by potent breakthrough discoveries. Nevertheless, the considerable potential of in vivo neuronal imaging at the micrometer-scale is far from being fully realized, in part because the exploitation of the wealth of experimental data is hampered by the lack of robust, fast automated analysis tools. We designed novel computational methods for the analysis of large-scale in vivo microscopy experiments and provided them to the community to promote this cutting-edge experimental field and advance our understanding of neuronal and cognitive processes. It will thus positively support the dissemination of knowledge and technologies in Europe.