P 16. Modulating emerging cortical activity with electric fields in brain slices

Abstract

During slow-wave-sleep (SWS) or deep anesthesia the EEG activity displays low frequency (<1 Hz), high amplitude low oscillatory rhythm mostly of cortical origin that was found to dominate slow wave sleep periods ( Steriade et al., 1993 ). This rhythm consists in an alternation of Up states (periods of cortical activation) and Down states (periods of silence). It is during Up states or active periods that activity synchronizes at least during some periods in beta and even gamma frequencies ( Steriade et al., 1996 , Hasenstaub et al., 2005 ). The advantage provided by cortical slices is that they contain an isolated cortical network, close to a two-dimensional one (400 μm thick) and with no inputs or outputs to other cortical areas or brain nuclei. Still, they contain enough network to generate slow oscillations ( Sanchez-Vives and McCormick, 2000 ) and even fast oscillations ( Compte et al., 2008 ). Transcranial brain stimulation through electric fields is nowadays being used for treatment in different neurological or psychiatric conditions. Benefits of brain stimulation are reported in numerous studies, however, the network and cellular mechanisms underlying these effects are not yet understood in detail. A preparation of active brain slices in vitro provides us the opportunity to analyze the modulation of the network dynamics by electric fields in an accessible and controlled way. Our objective has been to quantify the modulation of the emergent activity and network entrainment that we could achieve by exposing the cortical slices to a varying electric field. Slow oscillations were obtained from visual and prefrontal cortex slices as described in ( Sanchez-Vives, 2012 ). A uniform electric field was generated by passing current between two parallel AgCl-coated silver wires placed in parallel to the cortical layers. The intensity of the electric field was varied on time. Extracellular recordings of field potentials were obtained using tungsten electrodes or multielectrode arrays. The application of a constant current through the stimulating electrodes generates an electric field parallel to the apical-dendritic axis of pyramidal cortex neurons which is capable of depolarize or hyperpolarize the neuron’s resting membrane potentials. We find that electric fields of the appropriate orientation are indeed powerful modulators of the emergent activity patterns through excitability changes, in agreement with other authors ( Frohlich and McCormick, 2010 ). Furthermore, we obtain as well a systematic modulation of higher frequencies of oscillations within the beta and gamma ranges. These encouraging results suggest that proper manipulation of the electric fields can achieve highly specific spatio-temporal control of the activity. This provides a valuable testbed for the study of cortical stimulation of the intervention in different models of neurological alterations. Funded by BFU2011-27094 (Spain).