Nonlinear dendritic integration supports Up-Down states in single neurons

Abstract

AbstractChanges in the activity profile of cortical neurons are due to phenomena at the scale of local and long-range networks. Accordingly, the states of cortical neurons and their, often abrupt, transitions – a phenomenon known as Up/Down states – are attributed to variations in the afferent neurons’ activity. However, cellular physiology and morphology may also play a role. This study examines the impact of dendritic nonlinearities, in the form of voltage-gated NMDA receptors, on the response of cortical neurons to balanced excitatory/inhibitory synaptic inputs. Using a neuron model with two segregated dendritic compartments, we compare cells with and without dendritic nonlinearities. Our analysis shows that NMDA receptors boost somatic firing in the balanced condition and increase the correlation of membrane potentials across the three compartments of the neuron model. Then we introduce controlled fluctuations in excitatory inputs and quantify the ensuing bimodality of the somatic membrane potential. We show that dendritic nonlinearities are crucial for detecting these fluctuations and initiating Up-Down states whose shape and statistics closely resemble electrophysiological data. Our results provide new insights into the mechanisms underlying cortical bistability and highlight the complex interplay between dendritic integration and network dynamics in shaping neuronal behavior.Significance statementIn several physiological states, such as sleep or quiet wakefulness, the membrane of cortical cells shows a stereotypical bistability. The cell is either fully depolarized and ready to spike or in a silent, hyperpolarized state. This dynamics, known as Up-Down states, has often been attributed to changes in the network activity. However, whether cell-specific properties, such as dendritic nonlinearity, have a role in driving the neuron’s bistability remains unclear. This study examines the issue using a model of a pyramidal cell and reveals that the presence of dendritic NMDA receptors, drives the up-down states in response to small fluctuations in the network activity.