Deciphering the cortical output code – A multiscale approach to predictive brain modelling

To orchestrate complex behaviors in mammals, the cerebral cortex must continuously transmit its processing results to subcortical regions. While internal cortical processing relies on highly selective sparse codes, these descending cortical output streams employ an enigmatic dense code, characterized by high firing rates and low feature selectivity. This dense population code presents a profound paradox: how can downstream regions extract precise, cognitively relevant signals when most cortical output neurons can be active at any moment? We address this paradox by testing the hypothesis that cortex does not lose information when switching to a dense code. Instead, it utilizes a mechanism for sparse-to-dense coding transformations discovered by my laboratory: thalamocortical synapses target specifically the dendritic initiation zone for calcium action potentials (APs), which enables cortical output neurons to transmit multiple information streams simultaneously via a multiplexed 1-2-3 AP syntax. I will provide first evidence that this remarkable synaptic specificity and coding syntax generalize across long-range pathways. Information coupling via an anatomically and biophysically distinct dendritic nexus may hence be a ubiquitous mechanism for sparse-to-dense coding transformations in cortex. Dissecting these mechanistic origins of cortical output streams is only now possible due to a unique in vivo – in silico approach, perfected over two decades, that my laboratory developed for bridging the gaps between dendritic and population-level computations