Waking Up Dissociated Cultures of Cortical Neurons by Substituting Cholinergic Afferents
FENS Forum, Lisbon, July 2004
Dissociated cultures are attractive for the study of information processing in cortical networks because by growing them on multi-electrode arrays (MEAs), it is possible to have long-term, high-bandwidth, two-way communication between neurons and a computer. The spontaneous activity of such cultures is characterized by episodes of intense globally synchronized firing with longer periods of low-intensity dispersed activity. This pattern is more reminiscent of spindle waves than of awake cortex in vivo. Clearly, for studies of information processing, a model of awake cortex is more interesting than a model of sleeping cortex, so how can we “wake up” these cultures? In vivo, a key role in raising the cortical arousal level is played by cholinergic (ACh) afferents from the basal forebrain. We tested whether cortical cultures can be woken up by bathing them in 0.2 mM carbachol, a broad-spectrum ACh receptor agonist. This either abolished spontaneous bursting or dramatically reduced burst amplitudes, while increasing the overall culture-wide firing rate. The desynchronizing effect of carbachol in culture resembled the effect of cholinergic stimulation of cortex in vivo: a disruption of sleep waves giving rise to more awake-like patterns. When electrical stimulation was used to evoke activity, carbachol made the response strength much more consistent between applications of identical stimuli. Moreover, the probability that stimulation evokes bursts was reduced tenfold, while the number of spikes in the first 100 ms of the stimulus response was increased. We hypothesize that the more nearly stationary spontaneous activity observed in cortical cultures bathed in low concentrations of carbachol, together with the more consistent response to stimuli, is a much better substrate for information processing than the seizure-like activity of traditional deafferented cortical cultures. We will use these awakened cortical cultures to study learning and for robotic control.