Patterned stimulation leads in–vitro network into non-bursting state

Abstract

Abstract Spontaneous synchronized neuronal activity is found in the neocortical areas of the developing as well as epileptic brain. Synchronized neuronal activity can also be found in dissociated neural networks in vitro. To study the mechanistic origin of this behavior, we built a simple and fast computational model of large network of approximately 80% excitatory and 20% inhibitory neurons. Our model precisely matched the spike times and spike frequency adaptation of cortical pyramidal neurons obtained via whole cell recordings in confined in vitro networks. High accuracy of our model was achieved by implementing an AHP current with sigmoid dynamics that approximated Ca2+ dependent spike frequency adaptation. Then, we implemented short term synaptic depression of the synaptic weights. Modeling of depression was verified by matching the experimental post synaptic responses with three different frequencies of spikes evocation in the presynaptic neuron using dual whole cell recording. Investigations with this computational network were then verified in an all-optical experimental system. This experimental setup was designed by confining a cortical network with polydimethylsiloxane (PDMS), and by co-transfecting the neurons with channel-rhodopsin 2 (ChR2) and jRgeco1a. Patterned stimulator with spatial resolution of somatic compartment (approximately 15 μm) was used to excite individual neuron in a 2D confined network consisting of approximately 300 neurons confined to an area of about 1 mm2. We explored different stimulation paradigms in silico and in vitro to achieve a burst free neuronal network of different size by activating different numbers and patterns of input neurons. Action potential adaptation of each spiking excitatory neuron and the short term synaptic depression of each activated synapses could lead the network into a non-bursting mode. Distributed stimulation method that was developed in this work could potentially be used in suppressing epileptic seizures. Keywords: burst free network, patterned stimulation, optogenetics, synaptic depression