Leveraging heterogeneity for neural computation with fading memory in layer 2/3 cortical microcircuits

Complexity and heterogeneity are intrinsic to neurobiological systems, manifest in every process, at every scale, and are inextricably linked to the systems' emergent collective behaviours and function. However, the majority of studies addressing the dynamics and computational properties of biologically inspired cortical microcircuits tend to assume (often for the sake of analytical tractability) a great degree of homogeneity in both neuronal and synaptic/connectivity parameters. While simplification and reductionism are necessary to understand the brain's functional principles, disregarding the existence of the multiple heterogeneities in the cortical composition, which may be at the core of its computational proficiency, will inevitably fail to account for important phenomena and limit the scope and generalizability of cortical models. We address these issues by studying the individual and composite functional roles of heterogeneities in neuronal, synaptic and structural properties in a biophysically plausible layer 2/3 microcircuit model, built and constrained by multiple sources of empirical data. This approach was made possible by the emergence of large-scale, well curated databases, as well as the substantial improvements in experimental methodologies achieved over the last few years. Our results show that variability in single neuron parameters is the dominant source of functional specialization, leading to highly proficient microcircuits with much higher computational power than their homogeneous counterparts. We further show that fully heterogeneous circuits, which are closest to the biophysical reality, owe their response properties to the differential contribution of different sources of heterogeneity. Author summary Cortical microcircuits are highly inhomogeneous dynamical systems whose information processing capacity is determined by the characteristics of its heterogeneous components and their complex interactions. The high degree of variability that characterizes macroscopic population dynamics, both during ongoing, spontaneous activity and active processing states reflects the underlying complexity and heterogeneity which has the potential to dramatically constrain the space of functions that any given circuit can compute, leading to richer and more expressive information processing systems. In this study, we identify different tentative sources of heterogeneity and assess their differential and cumulative contribution to the microcircuit's dynamics and information processing capacity. We study these properties in a generic Layer 2/3 cortical microcircuit model, built and constrained by multiple sources of experimental data, and demonstrate that heterogeneity in neuronal properties and microconnectivity structure are important sources of functional specialization, greatly improving the circuit's processing capacity, while capturing various important features of cortical physiology.