Synchronization of neurons in micro-electrode array cultures

Abstract

A lot of methods were created in last decade for the spatio-temporal analysis of multi-electrode array (MEA) neuronal data sets. In this paper we show how a new simple analysis approach that considers the total network activity, is able to show interesting neuronal network system dynamical features. In particular, we perform two different analyses: a neuronal connectivity examination studying networks at different days in vitro (div) and an analysis of the long per- iod effects of the administration of two common neuroactive drugs, Tetrodotoxin (TTX) and D-2-amino-5-phosphonovalerate (AP5), to spontaneously spiking mature neuronal networks. Our analysis is performed considering burst topology, i.e., cataloguing network bursts as Global (if they involve more than the 25% of the MEA channels) or Local (if less that 25%). In the first analysis, this division allows to understand the network connectivity developments. The networking increases from div 1 to 6 building up an undifferentiated highly connected network. From div 6 to 10 the networking decreases (pruning) till reaching a plateau in a small-world like organization. The second analysis highlights substantial differences between long period effects of TTX and AP5. Results show that AP5, selectively blocking NMDA receptors and inhibiting long term potentiation, is unable to produce activity twisting in a network that already reached a developmental plateau, but it is able to desynchronize sub-network (Local) activity. TTX, on the other side, blocking any type of electrical communication among neurons, acts on the whole network synchronization. The important activity increment in the post-TTX epoch (+66%), together with the Global activity explosion, suggests the possibility of a long-term inhibitory-synapse depression mechanism.