Network plasticity in cortical assemblies

Abstract To investigate distributed synaptic plasticity at the cell assembly level, we used dissociated cortical networks from embryonic rats grown on grids of 60 extracellular substrate‐embedded electrodes (micro‐electrode arrays). We developed a set of experimental plasticity protocols based on the pairing of tetanic bursts (20 Hz) with low‐frequency stimuli (≤ 1 Hz), delivered through two separate channels of the array (i.e. associative tetanic stimulation). We tested our protocols on a large data set of 26 stable cultures, selected on the basis of both their initial level of spontaneous firing and the capability of low‐frequency test stimuli to evoke spikes. Our main results are summarized as follows: (i) low‐frequency stimuli produce neither short‐ nor long‐term changes in the evoked response of the network; (ii) associative tetanic stimulation is able to induce plasticity in terms of a significant increase or decrease of the evoked activity in the whole network; (iii) the amount of change (i.e. increase or decrease of the evoked firing) strongly depends on the specific features of the applied protocols; and (iv) the potentiation induced by a specific associative protocol can last several hours. The results obtained demonstrate that large in vitro cortical assemblies display long‐term network potentiation, a mechanism considered to be involved in the memory formation at cellular level. This pilot study could represent a relevant step towards understanding plastic properties at the neuronal population level.