Steve Potter, Jerry Pine and colleagues believe that a lack of normal input in high-density hippocampal cultures is the primary cause of synchronized bursting. By using MEA stimulation spread across several electrodes, they change the electrical behavior of the culture to show more dispersed spiking and less bursting. They suggest that these findings can be directly applied to epilepsy… interesting idea: epilepsy as a loss of normal cortical input to the epileptic focus. Click here for the entire article from this week’s J. Neurosci or below for the abstract.
Controlling Bursting in Cortical Cultures with Closed-Loop Multi-Electrode Stimulation
Daniel A. Wagenaar,1 Radhika Madhavan,2 Jerome Pine,1 and Steve M. Potter2
The Journal of Neuroscience, January 19, 2005, 25(3):680-688; doi:10.1523/JNEUROSCI.4209-04.2005
One of the major modes of activity of high-density cultures of dissociated neurons is globally synchronized bursting. Unlike in vivo, neuronal ensembles in culture maintain activity patterns dominated by global bursts for the lifetime of the culture (up to 2 years). We hypothesize that persistence of bursting is caused by a lack of input from other brain areas. To study this hypothesis, we grew small but dense monolayer cultures of cortical neurons and glia from rat embryos on multi-electrode arrays and used electrical stimulation to substitute for afferents. We quantified the burstiness of the firing of the cultures in spontaneous activity and during several stimulation protocols. Although slow stimulation through individual electrodes increased burstiness as a result of burst entrainment, rapid stimulation reduced burstiness. Distributing stimuli across several electrodes, as well as continuously fine-tuning stimulus strength with closed-loop feedback, greatly enhanced burst control. We conclude that externally applied electrical stimulation can substitute for natural inputs to cortical neuronal ensembles in transforming burst-dominated activity to dispersed spiking, more reminiscent of the awake cortex in vivo. This nonpharmacological method of controlling bursts will be a critical tool for exploring the information processing capacities of neuronal ensembles in vitro and has potential applications for the treatment of epilepsy.
Key words: bursting; dissociated culture; cortex; epilepsy; distributed stimulation; multi-electrode array; deep brain stimulation