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Low-Frequency Stimulation Induces Stable Transitions in Stereotypical Activity in Cortical Networks

Ildikó Vajda ^* , Jaap van Pelt ^*, Pieter Wolters ^¶, Michela Chiappalone , Sergio Martinoia , Eus van Someren   and Arjen van Ooyen ^*

^* Department of Experimental Neurophysiology, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, 1081 HV Amsterdam, The Netherlands; Department of Sleep and Cognition, Netherlands Institute for Neuroscience, 1105 BA Amsterdam, The Netherlands; Departments of Neurology, Clinical Neurophysiology and Medical Psychology, VU University Medical Center, Amsterdam, The Netherlands; Department of Biophysical and Electronic Engineering, University of Genoa, 16145 Genoa, Italy; and ^¶ Department of Neurons and Networks, Netherlands Institute for Neuroscience, 1105 BA Amsterdam, The Netherlands

Correspondence: Address reprint requests to Jaap van Pelt or Arjen van Ooyen, Dept. of Experimental Neurophysiology, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands. Tel.: 31-20-5987043 (J.v.P.), 31-20-5987090 (A.v.O); Fax: 31-20-5987112; E-mail: jaap.van.pelt{at}cncr.vu.nl, arjen.van.ooyen{at}cncr.vu.nl.

Reverberating spontaneous synchronized brain activity is believed to play an important role in neural information processing. Whether and how external stimuli can influence this spontaneous activity is poorly understood. Because periodic synchronized network activity is also prominent in in vitro neuronal cultures, we used cortical cultures grown on multielectrode arrays to examine how spontaneous activity is affected by external stimuli. Spontaneous network activity before and after low-frequency electrical stimulation was quantified in several ways. Our results show that the initially stable pattern of stereotypical spontaneous activity was transformed into another activity pattern that remained stable for at least 1 h. The transformations consisted of changes in single site and culture-wide network activity as well as in the spatiotemporal dynamics of network bursting. We show for the first time that low-frequency electrical stimulation can induce long-lasting alterations in spontaneous activity of cortical neuronal networks. We discuss whether the observed transformations in network activity could represent a switch in attractor state.