Increasing the physiological relevance of cortical culture experiments via embodiment and manipulation of endogenous cholinergic tone

Cortical cultures are increasingly implemented as an in vitro model of cortical networks for the study of network level learning and memory using planar multi-electrode arrays. However the recurrent, culture-wide synchronous activity (termed 'global bursts') exhibited by cortical cultures is not representative of the predominantly asynchronous activity characteristic of the intact cortex. Moreover, it has been demonstrated that such activity can interfere with the induction of plasticity and thus result in findings which cannot be related to networks in vivo. Critically, the mechanisms underlying such non-physiological global burst activity have been proposed to arise from incomplete development of the inhibitory network, as a result of the absence of afferent input during synaptic development. Therefore, the hypothesis that that re-introduction of afferent activity will, at least partially, rectify such developmental defects in the synaptic development is proposed. A recording environment was constructed to allow long term embodiment of a cortical culture using actuators and sensors of a mobile robot. Subsequently, the influence of electrical stimulation throughout synaptic development was investigated and found to alter spontaneous activity from global burst activity to a predominantly asynchronous state more comparable to that in vivo. Finally, the presence of significant endogenous, age dependent, cholinergic tone was demonstrated in these cultures and found to contain both muscarinic and nicotinic components. The presence of cholinergic tone and the striking comparability of its modulatory affect to that in vivo, increases the physiological relevance of the cortical culture platform, both within and outside of Animat paradigms. Moreover, such tone also provides a subtle and dynamic method by which plasticity and information flow could be experimentally modulated, in addition to overall excitability, in studies of mechanisms underlying learning and memory.EThOS - Electronic Theses Online ServiceGBUnited Kingdo