Multi-site Stimulation Quiets Network-wide Spontaneous Bursts and Enhances Functional Plasticity in Cultured Cortical Networks

Abstract

We culture high-density cortical cultures on multi-electrode arrays (MEAs), which allow us to stimulate and record from thousands of neurons. One of the modes of activity in these high-density cultures is dish-wide synchronized bursting. Unlike in vivo, these synchronized patterns persist for the lifetime of the culture. Such aberrant patterns of activity might be due to the fact that cortical cultures are sensory-deprived and arrested in development. We have devised methods to control this spontaneous activity by multi-electrode electrical stimulation and to study long-term functional neural plasticity, on a background of such burst-quieting stimulation. Here, we investigate whether burst quieting reveals long-term plasticity induced by tetanic stimulation. Spatio-temporal activity patterns (STAPs) that result from probe pulses were clustered and quantified in quieted and non-quieted cultures. Burst-quieted cultures show more tetanus-induced functional change than cultures which are allowed to express spontaneous bursts. The methods developed for this study will help in the understanding of network dynamics and appreciation of their role in long-term plasticity and information processing in the brain.