Monitoring in-vitro neural dynamics using high-density microelectrode arrays

Synaptic plasticity is thought to be the main process underlining how we learn, store memories, and even recover from injuries. With this term, we refer to the ability of the brain to change the strength of its synaptic connections in response to stimuli: an increase in the synaptic transmission is called potentiation, while a decrease results in what is named depression. One particular form of synaptic plasticity, called spike-timing dependent plasticity (STDP), emphasizes the temporal order and time interval between the presynaptic and postsynaptic potentials. In order to study the complex phenomena entailing neural plasticity, intracellular techniques for recording and stimulation have been extensively used. Although very powerful, they do not allow us to measure the electrical activity in a population of neurons; in addition, their invasive nature severely limits cell viability up to a few hours. To face these drawbacks, extracellular recording methods started to arise, since they enable non-invasively and simultaneously recording of neural activity from different sites. Thanks to the advancements in microtechnology, it is now possible to design high-density microelectrode arrays (HD-MEA), employing the complementary metal oxide semiconductor (CMOS) technology. Here, a newly developed CMOS HD-MEA is used with the goal of providing a new tool to study STDP. The HD-MEA features 59 760 microelectrodes, which is the largest number to date, arranged in a 4.48 x 2.43 mm2 sensing area with an inter-electrodic distance of 13.5 μm. The device was exploited to monitor the activity of rat cortical cell cultures in vitro, by recording the signal from the electrodes after having received Pt-black electrodeposition for noise reduction. The spike sorter Tridesclous was chosen to detect neurons on the chip and cross-correlogram analysis was performed to find pairs of potentially connected neurons. Nevertheless, cell viability and hardware issues did not allow us to assess STDP through stimulation. For these reasons, the results from spontaneous electrophysiological recording and stimulation in saline solution show the limits of the device and the necessity of a new culturing protocol to be developed, with the aim of exploiting all the potentiality this HD-MEA can offer to neuroscientists.