PT - JOURNAL ARTICLE AU - Yann Sweeney AU - Jeanette Hellgren Kotaleski AU - Matthias H. Hennig TI - A diffusive homeostatic signal maintains neural heterogeneity and responsiveness in cortical networks AID - 10.1101/011957 DP - 2015 Jan 01 TA - bioRxiv PG - 011957 4099 - http://biorxiv.org/content/early/2015/02/19/011957.1.short 4100 - http://biorxiv.org/content/early/2015/02/19/011957.1.full AB - Gaseous neurotransmitters such as nitric oxide (NO) provide a unique and often overlooked mechanism for neurons to communicate through diffusion within a network, independent of synaptic connectivity. NO provides homeostatic control of intrinsic excitability. Here we conduct a theoretical investigation of the distinguishing roles of NO-mediated diffusive homeostasis in comparison with canonical non-diffusive homeostasis in cortical networks. We find that both forms of homeostasis provide a robust mechanism for maintaining stable activity following perturbations. However, the resulting networks differ, with diffusive homeostasis maintaining substantial heterogeneity in activity levels of individual neurons, a feature disrupted in networks with non-diffusive homeostasis. This results in networks capable of representing input heterogeneity, and linearly responding over a broader range of inputs than those undergoing non-diffusive homeostasis. We further show that these properties are preserved when homeostatic and Hebbian plasticity are combined. These results suggest a mechanism for dynamically maintaining neural heterogeneity, and expose computational advantages of non-local homeostatic processes.Author Summary Neural firing rates must be maintained within a stable range in the face of ongoing fluctuations in synaptic connectivity. Existing cortical network models achieve this through various homeostatic mechanisms which constrain the excitability of individual neurons according to their recent activity. Here, we propose a new mechanism, diffusive homeostasis, in which neural excitability is modulated by nitric oxide, a gas which can flow freely across cell membranes. Information about a neurons’ firing rate can be carried by nitric oxide, meaning that an individual neurons’ excitability is affected by neighboring neurons’ firing rates as well as its own. We find that this allows a neuron to deviate from the target population activity, as its neighbors will counteract this deviation, thus maintaining stable average activity. This form of neural heterogeneity is more flexible than assigning different target firing rates to individual neurons.