No abstract

The prefrontal cortex is centrally involved in a wide range of cognitive functions and their impairment in psychiatric disorders. Yet, the computational principles that govern the dynamics of prefrontal neural networks, and link their physiological, biochemical and anatomical properties to cognitive functions, are not well understood. Computational models can help to bridge the gap between these different levels of description, provided they are sufficiently constrained by experimental data and capable of predicting key properties of the intact cortex. Here, we present a detailed network model of the prefrontal cortex, based on a simple computationally efficient single neuron model (simpAdEx), with all parameters derived from in vitro electrophysiological and anatomical data. Without additional tuning, this model could be shown to quantitatively reproduce a wide range of measures from in vivo electrophysiological recordings, to a degree where simulated and experimentally observed activities were statistically indistinguishable. These measures include spike train statistics, membrane potential fluctuations, local field potentials, and the transmission of transient stimulus information across layers. We further demonstrate that model predictions are robust against moderate changes in key parameters, and that synaptic heterogeneity is a crucial ingredient to the quantitative reproduction of in vivo-like electrophysiological behavior. Thus, we have produced a physiologically highly valid, in a quantitative sense, yet computationally efficient PFC network model, which helped to identify key properties underlying spike time dynamics as observed in vivo, and can be harvested for in-depth investigation of the links between physiology and cognition.

Sensory systems constantly compare external sensory information with internally generated predictions. While neural hallmarks of prediction errors have been found throughout the brain, the circuit-level mechanisms that underlie their computation are still largely unknown. Here, we show that a well-orchestrated interplay of three interneuron types shapes the development and refinement of negative prediction-error neurons in a computational model of mouse primary visual cortex. By balancing excitation and inhibition in multiple pathways, experience-dependent inhibitory plasticity can generate different variants of prediction-error circuits, which can be distinguished by simulated optogenetic experiments. The experience-dependence of the model circuit is consistent with that of negative prediction-error circuits in layer 2/3 of mouse primary visual cortex. Our model makes a range of testable predictions that may shed light on the circuitry underlying the neural computation of prediction errors.