Modeling and simulating neuromodulatory organization in the Neocortex

Description

Abstract

The hindlimb representation in the somatosensory cortex of two-week old Wistar rats has been a valuable model system for dissecting the microcircuitry of neurons and their synaptic connections. In this study, we quantified the fiber length per cortical volume and the density of varicosities for cholinergic, catecholaminergic and serotonergic neuromodulatory systems within the cortical neuropil using immunocytochemical staining and stereological techniques. Acquired data were integrated into a biophysically detailed computational model of the somatosensory cortex to provide new insights into the anatomical organization of neuromodulatory innervation and the effects of their release in shaping neocortical activity. We found that neuromodulatory innervation, although sparse, substantially impacts network activity. Network simulations support the hypothesis that acetylcholine suppresses slow oscillations and promotes the desynchronization of cortical networks, consistent with the extensive findings in existing literature. Additionally, the temporal properties of acetylcholine modulation are consistent with synaptic rather than volume release. Furthermore, we predict that the release of dopamine and serotonin in sensory cortices induces network desynchronization by inhibiting delta oscillations and that serotonin also initiates the emergence of theta oscillations, thus unveiling previously unexplored aspects of their function in governing cortical network activity. The experimental data and the biophysical computational model are available as an open-access community resource.

Technical info

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