Role of spontaneous bursts in functional plasticity and spatiotemporal dynamics of dissociated cortical cultures
MetadataShow full item record
What changes in our brain when we learn? This is perhaps the most intriguing question of science in this century. In an attempt to learn more about the inner workings of neural circuitry, I studied cultured 2-dimensional networks of neurons on multi-electrode arrays (MEAs). MEAs are ideal tools for studying long-term neural ensemble activity because many individual cells can be studied continuously for months, through electrical stimulation and recording. One of the most prominent patterns of activity observed in these cultures is network-wide spontaneous bursting, during which most of the active electrodes in the culture show elevated firing rates. We view the persistence of spontaneous bursting in vitro as a sign of arrested development due to deafferentation. Substituting distributed electrical stimulation for afferent input transformed the activity in dissociated cultures from bursting to more dispersed spiking, reminiscent of activity in the adult brain. Burst suppression reduced the variability in neural responses making it easier to induce and detect functional plasticity caused by tetanic stimulation. This suggests that spontaneous bursts interfere with the effects of external stimulation and that a burst-free environment leads to more stable connections and predictable effects of tetanization. Moreover, our culture models continuously receive input stimulation in the form of background electrical stimulation, and so better resemble the intact brain than isolated (non-continuously stimulated) cultures. The proportion of GABAergic neurons in the cultures was significantly increased (p<1e-2, paired t-test) after burst-quieting for 2 days, suggesting that burst suppression operated through the homeostatic control of inhibitory neurotransmitter levels. We also studied the role of spontaneous bursts as potential carriers of information in the network by clustering these spatiotemporally diverse bursts. Spontaneous burst clusters were stable over hours and tetanic stimulation significantly reorganized the distribution of the clusters. In summary, this body of work explores the rules of network-level functional plasticity and provides the input (electrical stimulation) output (spatiotemporal patterns) mappings for behavioral studies in embodied hybrid systems. The results of this study may also have clinical implications in the development of sensory prostheses and treatment of diseases of aberrant network activity such as epilepsy.